A multicentre, adaptive, randomized blinded controlled trial of the safety and efficacy of investigational therapeutics for the treatment of COVID-19 in hospitalized adults – version for European Union/United Kingdom sites
Latest Information Update: 02 Feb 2024
At a glance
- Drugs Baricitinib (Primary) ; Remdesivir (Primary)
- Indications COVID 2019 infections
- Focus Registrational; Therapeutic Use
- Acronyms ACTT; ACTT I; ACTT-EU-UK; NIAID-ACTT
Most Recent Events
- 19 Jul 2023 Results published in the Journal of Infectious Diseases
- 29 Nov 2022 Results post hoc of analysis compared recovery and mortality between these comparable sequential cohorts of patients who received remdesivir plus SOC, adjusting for baseline characteristics with propensity score weighting published in the Annals of Internal Medicine
- 19 Aug 2021 Results(n=1051) assessing the dynamics of clinical progression changed along 4 pathways: recovery, improvement in respiratory therapy requirement, deterioration in respiratory therapy requirement, and death published in the Clinical Infectious Diseases
Trial Overview
Outcome
Purpose
This phase III, placebo-controlled trial is designed to evaluate the safety and efficacy of novel therapeutic agents (Remdesivir) in hospitalized adults diagnosed with COVID-19.
The study is comparing different investigational therapeutic agents to a control arm. There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms. To evaluate the clinical efficacy, as assessed by time to recovery, of different investigational therapeutics as compared to the control arm.
Comments
According to a Gilead Sciences media release, the U.S. Food and Drug Administration (FDA) has approved Veklury (remdesivir) for the treatment of patients with COVID-19 requiring hospitalization, based on data from ACTT-1 and SIMPLE-Severe studies.
According to a Gilead Sciences media release, the European Commission granted conditional marketing authorization of Veklury on July 3, 2020, based on data from this trial.
The Japanese Ministry of Health, Labour and Welfare (MHLW) granted regulatory approval of Veklury (remdesivir) as a treatment for SARS-CoV-2 infection under an exceptional approval pathway. The exceptional approval was granted due to the COVID-19 pandemic and references the Emergency Use Authorization of remdesivir in the United States. The approval is based on clinical data from the U.S. National Institute of Allergy and Infectious Diseases's global Phase 3 trial, the company's Phase 3 SIMPLE trial in patients with severe manifestations of COVID-19, and available data from company's compassionate use program, including patients in Japan.
The USA Food and Drug Administration (FDA) has expanded the Emergency Use Authorization (EUA) use of the investigational antiviral Veklury (remdesivir) to treat all hospitalized patients with COVID-19. The expansion of the scope of the EUA to include hospitalized patients with mild or moderate COVID-19 is supported by the Agency's analysis of additional data from two randomized, controlled clinical trials that included patients with mild or moderate disease (ACTT-1 and Study GS-US-540-5774). The EUA will facilitate broader use of remdesivir to treat hospitalized patients with severe COVID-19 disease, enabling access to remdesivir at additional hospitals across the country. Under the EUA, both 5-day and 10-day treatment durations are suggested, based on the severity of disease.The EUA is temporary and does not take the place of the formal new drug application submission, review and approval process. The EUA allows for the distribution and emergency use of remdesivir only for the treatment of COVID-19, remdesivir remains an investigational drug and has not been approved by FDA.
Primary Endpoints
Time to recovery
description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.
time_frame: Day 1 through Day 29 [1]
Other Endpoints
Change From Baseline in Alanine Transaminase (ALT)
description: Blood to evaluate ALT was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
time_frame: Days 1, 3, 5, 8, 11, 15 and 29
Change From Baseline in Aspartate Transaminase (AST)
description: Blood to evaluate AST was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
time_frame: Days 1, 3, 5, 8, 11, 15 and 29
Change From Baseline in Creatinine
description: Blood to evaluate serum creatinine was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
time_frame: Days 1, 3, 5, 8, 11, 15 and 29
Change From Baseline in Glucose
description: Blood to evaluate serum glucose was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
time_frame: Days 1, 3, 5, 8, 11, 15 and 29
Change From Baseline in Hemoglobin
description: Blood to evaluate hemoglobin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
time_frame: Days 1, 3, 5, 8, 11, 15 and 29
Change From Baseline in Platelets
description: Blood to evaluate platelets was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
time_frame: Days 1, 3, 5, 8, 11, 15 and 29
Change From Baseline in Prothrombin Time (PT)
description: Blood to evaluate PT was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
time_frame: Days 1, 3, 5, 8, 11, 15 and 29
Change From Baseline in Total Bilirubin
description: Blood to evaluate total bilirubin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
time_frame: Days 1, 3, 5, 8, 11, 15 and 29
Change From Baseline in White Blood Cell Count (WBC)
description: Blood to evaluate WBC was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
time_frame: Days 1, 3, 5, 8, 11, 15 and 29
Change From Baseline in Neutrophils
description: Blood to evaluate neutrophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
time_frame: Days 1, 3, 5, 8, 11, 15 and 29
Change From Baseline in Lymphocytes
description: Blood to evaluate lymphocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
time_frame: Days 1, 3, 5, 8, 11, 15 and 29
Change From Baseline in Monocytes
description: Blood to evaluate monocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
time_frame: Days 1, 3, 5, 8, 11, 15 and 29
Change From Baseline in Basophils
description: Blood to evaluate basophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
time_frame: Days 1, 3, 5, 8, 11, 15 and 29
Change From Baseline in Eosinophils
description: Blood to evaluate eosinophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
time_frame: Days 1, 3, 5, 8, 11, 15 and 29
Change in National Early Warning Score (NEWS) From Baseline
description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome.
time_frame: Days 1, 3, 5, 8, 11, 15, 22, and 29
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 1
description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
time_frame: Day 1
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 3
description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
time_frame: Day 3
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 5
description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
time_frame: Day 5
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 8
description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
time_frame: Day 8
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 11
description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
time_frame: Day 11
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 15
description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
time_frame: Day 15
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 22
description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
time_frame: Day 22
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 29
description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
time_frame: Day 29
Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs)
description: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.
time_frame: Day 1 through Day 29
Percentage of Participants Reporting Serious Adverse Events (SAEs)
description: An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
time_frame: Day 1 through Day 29
Percentage of Participants Discontinued or Temporarily Suspended From Investigational Therapeutics
description: Participants may have been discontinued from investigational therapeutics due to discharge or death. The halting or slowing of the infusion for any reason was collected, as was missed doses in the series of 10 doses.
time_frame: Day 1 through Day 10
Duration of Hospitalization
description: Duration of hospitalization was determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die.
time_frame: Day 1 through Day 29
Duration of New Non-invasive Ventilation or High Flow Oxygen Use
description: Duration of new non-invasive ventilation or high flow oxygen use was measured in days among participants who were not on non-invasive ventilation or high-flow oxygen use at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die
time_frame: Day 1 through Day 29
Duration of New Oxygen Use
description: Duration of new oxygen use was measured in days among participants who were not on oxygen at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die
.
time_frame: Day 1 through Day 29
Duration of New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use
description: Duration of new ventilator or ECMO use was measured in days among participants who were not on a ventilator or ECMO at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die
time_frame: Day 1 through Day 29
Percentage of Participants Requiring New Non-invasive Ventilation or High-flow Oxygen Use
description: New non-invasive ventilation or high-flow oxygen use was determined as the percentage of subject not on non-invasive ventilation or high-flow oxygen at baseline.
time_frame: Day 1 through Day 29
Percentage of Participants Requiring New Oxygen Use
description: The percentage of participants requiring new oxygen use was determined as the percentage of participants not requiring oxygen at baseline
time_frame: Day 1 through Day 29
Percentage of Participants Requiring New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use
description: The percentage of participants requiring new ventilator or ECMO use was determined as the percentage not on a ventilator or ECMO at baseline
time_frame: Day 1 through Day 29
Mean Change in the Ordinal Scale
description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. A positive change indicates a worsening and a negative change is an improvement.
time_frame: Day 1, 3, 5, 8, 11, 15, 22, and 29
14-day Participant Mortality
description: The mortality rate was determined as the proportion of participants who died by study Day 15.
time_frame: Day 1 through Day 15
29-day Participant Mortality
description: The mortality rate was determined as the proportion of participants who died by study Day 29.
time_frame: Day 1 through Day 29
Time to an Improvement by at Least One Category Using an Ordinal Scale
description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. Time to improvement by at least one category was determined for each participant
time_frame: Day 1 through Day 29
Time to an Improvement of at Least Two Categories Using an Ordinal Scale
description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. Time to improvement by at least two categories was determined for each participant
time_frame: Day 1 through Day 29
Time to Discharge or to a NEWS of 2 or Less and Maintained for 24 Hours, Whichever Occurs First
description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome. The time to discharge or a NEWS of less than or equal to 2 was determined for each participant.
time_frame: Day 1 through Day 29 [2]
Diseases Treated
| Indication | Qualifiers | Patient Segments |
|---|---|---|
| COVID 2019 infections | treatment | - |
Subjects
- Subject Type patients
-
Number
Planned: 1032
Actual: 1062
- Sex male & female
- Age Group 18-99 years (mean age -58.9 years); adult; elderly
Patient Inclusion Criteria
1. Admitted to a hospital with symptoms suggestive of COVID-19 infection. 2. Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures. 3. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures. 4. Male or non-pregnant female adult > / = 18 years of age at time of enrollment. 5. Has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay in any specimen, as documented by either or the following: 1. PCR positive in sample collected < 72 hours prior to randomization; OR
Patient Exclusion Criteria
2. PCR positive in sample collected >/= 72 hours prior to randomization, documented inability to obtain a repeat sample (e.g. due to lack of testing supplies, limited testing capacity, results taking >24 hours, etc.) AND progressive disease suggestive of ongoing SARS-CoV-2 infection. 6. Illness of any duration, and at least one of the following: 1. Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR 2. SpO2 < / = 94% on room air, OR 3. Requiring supplemental oxygen, OR 4. Requiring mechanical ventilation. 7. Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception not including hormonal contraception from the time of screening through Day 29. 8. Agrees to not participate in another clinical trial for the treatment of COVID-19 or SARS-CoV-2 through Day 29. 1. Alanine Transaminase (ALT) or Aspartate Transaminase (AST) > 5 times the upper limit of normal. 2. Estimated glomerular filtration rate (eGFR) < 30 ml/min (including patients receiving hemodialysis or hemofiltration). 3. Pregnancy or breast feeding. 4. Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours. 5. Allergy to any study medication.
Trial Details
Identifiers
| Identifier | Owner |
|---|---|
| NCT04280705 | ClinicalTrials.gov: US National Institutes of Health |
| EudraCT2020-001052-18 | European Clinical Trials Database |
| 13035264 | ISRCTN: Current Controlled Trials |
| U1111-1249-9599 | World Health Organisation |
| 20-0006 | - |
| INSIGHTPROTOCOL010 | - |
| 010 | - |
| 20SC0154 | - |
| DMID-Protocol-Number20-0006INSIGHT-Protocol-Number010UPHR - CPMS | - |
Organisations
- Affiliations Gilead Sciences
Trial Dates
-
Initiation Dates
Planned : 12 Mar 2020
Actual : 21 Feb 2020
-
Primary Completion Dates
Planned : 01 Apr 2023
Actual : 21 May 2020
-
End Dates
Planned : 01 Apr 2023
Actual : 21 May 2020
Substudies/Extensions
Sub-study: Immune profiling reveals early disease trajectories associated with COVID-19 mortality
Other Details
- Design double-blind; multicentre; open; parallel; prospective; randomised
- Phase of Trial Phase III
- Location Denmark; England; Germany; Greece; Italy; Japan; Mexico; Poland; Portugal; Singapore; South Korea; Spain; United Kingdom; USA
- Focus Registrational; Therapeutic Use
Interventions
| Drugs | Route | Formulation | Target |
|---|---|---|---|
|
Baricitinib Primary Drug
|
Oral | Tablet | Janus kinase 1, Janus kinase 2, TYK2 kinase |
|
Remdesivir Primary Drug
|
Intravenous | Infusion, Injection, Lyophilised | RNA-dependent RNA polymerase |
Placebo
200 mg of Remdesivir placebo administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir placebo while hospitalized for up to a 10 days total course. n=286. Other: Placebo (The supplied placebo lyophilized formulation is identical in physical appearance to the active lyophilized formulation and contains the same inactive ingredients. Alternatively, a placebo of normal saline of equal volume may be given if there are limitations on matching placebo supplies.)
Remdesivir
200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10 days total course. n=286. Drug: Remdesivir (Drug Remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524. In addition to the active ingredient, the lyophilized formulation of Remdesivir contains the following inactive ingredients: water for injection, sulfobutylether beta-cyclodextrin sodium (SBECD), and hydrochloric acid and/or sodium hydroxide.)
Results
Therapeutic efficacy
Final results from the phase III ACTT-1 trial showed that the primary endpoint was met with remdesivir plus standard of care demonstrating superiority in shortening the time to recovery through Day 29 compared with placebo plus standard of care. In the final Day 29 results, patients receiving remdesivir (n = 541) achieved clinical recovery five days faster than those receiving placebo, with a median time to recovery of 10 days with remdesivir and 15 days with placebo and an increased recovery rate by 29% compared with placebo (rate ratio for recovery, 1.29; 95% confidence interval [CI], 1.12 to 1.49; p<0.001). In patients who required oxygen support at baseline (n = 957)patients receiving remdesivir achieved clinical recovery seven days faster than those receiving placebo, with a median time to recovery of 11 days with remdesivir and 18 days with placebo (rate ratio for recovery, 1.31; 95% CI, 1.12 to 1.52). Patients receiving remdesivir demonstrated a 50% more likelihood to have improved by Day 15 compared with those receiving placebo (OR, 1.5; 95% CI, 1.2 to 1.9), and the effect was maintained through Day 29. Also, reduction in disease progression was observed in patients with oxygen requirement. This resulted in low incidence of new mechanical ventilation or ECMO (13% vs. 23%; 95% CI, -15 to -4). The benefit of remdesivir was found to be greater when given within 10 days of symptom onset. In the overall study population, a trend towards reduced mortality at Day 15 (6.7% vs. 11.9%; HR, 0.55; 95% CI, 0.36 to 0.83) and Day 29 (11.4% vs. 15.2%, HR 0.73; 95% CI, 0.52 to 1.03) was observed in remdesivir -treated patients compared with placebo [3] [1] . Earlier reported results from the trial demonstrated that administration of remdesivir statistically and significantly improved clinical odds at day 15 as compared to placebo group. The time for recovery as well as odds of improvement at day 15 were favourable for remdesivir group and consistent with overall study results. Earlier results demonstrated that patients treated with remdesivir recovered after about 10 days, compared with 15 days for patients given placebo. In patients with mild to moderate disease this effect was not observed, where time to recovery was 5 days for both the remdesivir group and the placebo group. Approximately 90% of the study population constituted patients with severe disease, where in time to recovery was 12 days in the remdesivir group and 18 days in the placebo group. However, no difference was observed in time to recovery in patients who started remdesivir when they were already on mechanical ventilation or extracorporeal membrane oxygenation (ECMO). Data on the proportion of patients who died up to 28 days after starting treatment are currently being collected for final analysis. Initial preliminary results from the trial showed that treatment with remdesivir exhibited 31% of recovery from hospitalised patients (n = 1063) than those who received the placebo and suggested a survival benefit with mortality rate of 8.0% for the remdesivir group versus 11.6% for the placebo group [4] [5] .
Adverse events
In the phase III ACTT-1 trial, treatment with remdesivir was found to be generally safe and well tolerated. Overall, the incidence of adverse events associated with remdesivir was similar to placebo, with no new safety signals identified. Rates of serious adverse events (SAEs) were numerically higher in the placebo group compared with the remdesivir group (PBO + SOC: 32%; Veklury + SOC: 25%). Treatment discontinuation, all cause grade 3 and 4 adverse events and laboratory abnormalities were similar across groups [1] .
Publications
-
Gilead Sciences. Final Results of National Institute of Allergy and Infectious Diseases ACTT-1 Trial Published in New England Journal of Medicine Expand Clinical Benefits of Veklury(Rm) (remdesivir) for the Treatment of COVID-19. Media-Rel 2020;.
Media Release -
EvergreenHealth. EvergreenHealth Prepares for Second Arm of Clinical Trial After Initial Findings Show Promising Results for Remdesivir as Potential Treatment for COVID-19. Media-Rel 2020;.
Media Release -
Paules CI, Gallagher SK, Rapaka RR, Davey RT, Doernberg SB, Grossberg R, et al. Remdesivir for the prevention of invasive mechanical ventilation or death in COVID-19 - A post-hoc analysis of the Adaptive COVID-19 Treatment Trial-1 Cohort Data. . Clin-Infect-Dis 2021;.
PubMed | CrossRef Fulltext -
Hedskog C, Rodriguez L, Beigel JH, Dempsey W, Greninger AL, Roychoudhury P, et al. Resistance Analyses of Patient Viral Samples from the Remdesivir Phase 3 Adaptive COVID-19 Treatment Trial-1 (ACTT-1). IDW-2022 2022; abstr. 1149.
Available from: URL: https://academic.oup.com/ofid/article/9/Supplement_2/ofac492.987/6903133 -
Fintzi J, Bonnett T, Sweeney DA, Huprikar NA, Ganesan A, Frank MG, et al. Deconstructing the Treatment Effect of Remdesivir in the Adaptive COVID-19 Treatment Trial-1: Implications for Critical Care Resource Utilization. . Clin-Infect-Dis 2021;.
PubMed | CrossRef Fulltext -
Potter GE, Bonnett T, Rubenstein K, Lindholm DA, Rapaka RR, Doernberg SB, et al. Temporal Improvements in COVID-19 Outcomes for Hospitalized Adults: A Post Hoc Observational Study of Remdesivir Group Participants in the Adaptive COVID-19 Treatment Trial. . Ann-Intern-Med 2022;.
PubMed | CrossRef Fulltext -
Paladugu S, Donato AA. Remdesivir improved time to recovery in adults hospitalized with COVID-19 and lower respiratory tract involvement. . Ann-Intern-Med 2020;173(2):JC4.
PubMed | CrossRef Fulltext -
Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the Treatment of Covid-19 - Preliminary Report. . N-Engl-J-Med 2020;.
PubMed | CrossRef Fulltext -
Hedskog C, Rodriguez L, Roychoudhury P, Huang ML, Jerome KR, Hao L, et al. Viral Resistance Analyses From the Remdesivir Phase 3 Adaptive COVID-19 Treatment Trial-1 (ACTT-1). . J-Infect-Dis 2023;.
PubMed | CrossRef Fulltext -
Thiede JM, Gress AR, Libby SD, Ronayne CE, Matchett WE, Noren B, et al. Immune profiling reveals early disease trajectories associated with COVID-19 mortality: a sub-study from the ACTT-1 trial. . J-Infect-Dis 2021;.
PubMed | CrossRef Fulltext -
Force L, Blair C, Duckworth J, Abdelghany M, Nguyen N, Hyland RH, et al. Hepatic Safety of Remdesivir Across Phase 3 Placebo-controlled COVID-19 Studies. IDW-2023 2023; abstr. 524.
Available from: URL: https://academic.oup.com/ofid/article/10/Supplement_2/ofad500.593/7448787 -
Singh K, Rubenstein K, Callier V, Shaw-Saliba K, Rupert A, Dewar RL, et al. Viral and Immunologic biomarkers of COVID-19 improve risk stratification and identify patients most likely to benefit from therapy with remdesivir. IDW-2022 2022; abstr. 789.
Available from: URL: https://academic.oup.com/ofid/article/9/Supplement_2/ofac492.050/6902254
Trial Centres
Investigators
| Investigator | Centre Name | Trial Centre Country |
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13017617948 DMIDClinicalTrials@niaid.nih.gov
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Centres
| Centre Name | Location | Trial Centre Country |
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| AHEPA University Hospital - 1st Department of Internal Medicine | Thessaloniki, Central Macedonia | Greece |
| Atlanta VA Medical Center - Infectious Diseases Clinic | Decatur, Georgia | USA |
| Baylor College of Medicine - Molecular Virology and Microbiology | Houston, Texas | USA |
| Brooke Army Medical Center | Fort Sam Houston, Texas | USA |
| Cedars Sinai Medical Center | West Hollywood, California | USA |
| Changi General Hospital - Clinical Trials and Research Unit (CTRU) | Singapore | Singapore |
| Denver Health Division of Hospital Medicine - Main Campus | Denver, Colorado | USA |
| Duke Human Vaccine Institute - Duke Vaccine and Trials Unit | Durham, North Carolina | USA |
| Emory Vaccine Center - The Hope Clinic | Decatur, Georgia | USA |
| EvergreenHealth Infectious Disease Service | Kirkland, Washington | USA |
| Hospital Clinic Barcelona, Servicio de Salud Internacional | Barcelona, Cataluña | Spain |
| Hospital Germans Trias i Pujol - Servei Malalties Infeccioses | Barcelona, Cataluña | Spain |
| Hospital of the University of Pennsylvania - Infectious Diseases | Philadelphia, Pennsylvania | USA |
| Instituto Nacional de Ciencias Medicas y Nutrición Salvador Zubirán - Departamento de Infectologia | Mexico City | Mexico |
| Instituto Nacional de Enfermedades Respiratorias (INER) - Ismael Cosío Villegas | Mexico City | Mexico |
| John Radcliffe Hospital | Headington, Oxford | United-Kingdom |
| Johns Hopkins Hospital - Medicine - Infectious Diseases | Baltimore, Maryland | USA |
| Khoo Teck Puat Hospital - Clinical Research Unit | Singapore | Singapore |
| Madigan Army Medical Center - Infectious Disease Clinic | Tacoma, Washington | USA |
| Massachusetts General Hospital - Infectious Diseases | Boston, Massachusetts | USA |
| Medical School of Athens University - Evangelismos Hospital - Department of Critical Care and Pulmonary Services | Athens | Greece |
| Montefiore Medical Center - Infectious Diseases | Bronx, New York | USA |
| National Center for Global Health and Medicine Hospital - Disease Control and Prevention Center | Tokyo | Japan |
| National Centre for Infectious Diseases (NCID) | Singapore | Singapore |
| National Institute of Allergy and Infectious Diseases (NIAID) |
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| National Institutes of Health - Clinical Center, National Institute of Allergy and Infectious Diseases Laboratory Of Immunoregulation, Clinical Research Section | Bethesda, Maryland | USA |
| National University Health System - Division of Infectious Diseases | Singapore | Singapore |
| Naval Medical Center Portsmouth - Infectious Disease Division | Portsmouth, Virginia | USA |
| Naval Medical Center San Diego - Infectious Disease Clinic | San Diego, California | USA |
| New York University School of Medicine - Langone Medical Center - Microbiology - Parasitology | New York, New York | USA |
| Ng Teng Fong General Hospital - Infectious Disease Service | Singapore | Singapore |
| Northwestern Hospital - Infectious Disease | Chicago, Illinois | USA |
| Penn State Health Milton S. Hershey Medical Center - Division of Infectious Diseases | Hershey, Pennsylvania | USA |
| Providence Sacred Heart Medical Center | Spokane, Washington | USA |
| Regents of the University of Minnesota |
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| Rocky Mountain Regional Veteran Affairs Medical Center - Department of Infectious Diseases | Aurora, Colorado | USA |
| Royal Sussex County Hospital - Department of Intensive Care Medicine | East Sussex, Brighton | United-Kingdom |
| Royal Victoria Infirmary - Department of Infectious Diseases | Level 6, Ward 19, Newcastle Upon Tyne | United-Kingdom |
| Saint Louis University - Center for Vaccine Development | Saint Louis, Missouri | USA |
| Saint Thomas' Hospital - Directorate of Infection | London, London, City Of | United-Kingdom |
| Seoul National University Bundang Hospital - Division of Infectious Diseases | Bundang-gu Seongnam-si, Gyeonggi-do | South-Korea |
| Seoul National University Hospital | Seoul, Jongno-gu | South-Korea |
| Singapore General Hospital - Department of Infectious Diseases | Singapore | Singapore |
| Southeast Louisiana Veterans Health Care System (SLVHCS) - Section of Infectious Diseases | New Orleans, Louisiana | USA |
| St. James's University Hospital - Infectious Diseases | Leeds, West Yorkshire | United-Kingdom |
| Stanford University - Stanford Hospital and Clinics - Pediatrics - Infectious Diseases | Palo Alto, California | USA |
| The University of Washington - Virology Research Clinic | Seattle, Washington | USA |
| Universitatsklinikum Bonn, Medizinische Klinik I - Bereich Infektiologie/HIV der Medizinischen Klinik | Bonn, Nordrhein-Westfalen | Germany |
| Universitatsklinikum Koeln Klinik I fur Innere Medizin Klinisches Studienzentrum fur Infektiologie I | Cologne | Germany |
| University of Alabama at Birmingham School of Medicine - Infectious Disease | Birmingham, Alabama | USA |
| University of California Davis Medical Center - Internal Medicine - Infectious Disease | Sacramento, California | USA |
| University of California Irvine Medical Center - Infectious Disease | Orange, California | USA |
| University of California Los Angeles Medical Center - Westwood Clinic | Los Angeles, California | USA |
| University of California San Diego Health - Jacobs Medical Center | La Jolla, California | USA |
| University of California San Francisco - Zuckerberg San Francisco General Hospital - Division of Human Immunodeficiency Virus, Infectious Disease, and Global Medicine | San Francisco, California | USA |
| University of Copenhagen - Centre of Excellence for Health, Immunity and Infections (CHIP) - Department of Infectious Diseases | Copenhagen | Denmark |
| University of Florida Health - Shands Hospital - Division of Infectious Diseases and Global Medicine | Gainesville, Florida | USA |
| University of Illinois at Chicago College of Medicine - Division of Infectious Diseases | Chicago, Illinois | USA |
| University of Maryland School of Medicine - Center for Vaccine Development - Baltimore | Annapolis, Maryland | USA |
| University of Massachusetts Medical School - Infectious Diseases and Immunology | Worcester, Massachusetts | USA |
| University of Minnesota Medical Center, Fairview - Infectious Diseases and International Medicine | Minneapolis, Minnesota | USA |
| University of Nebraska Medical Center - Infectious Diseases | Omaha, Nebraska | USA |
| University of Pennsylvania Perelman School of Medicine - Penn Institute for Immunology | Philadelphia, Pennsylvania | USA |
| University of Rochester Medical Center - Vaccine Research Unit | Rochester, New York | USA |
| University of Texas Health Science Center at San Antonio - Infectious Diseases | San Antonio, Texas | USA |
| University of Texas Medical Branch - Division of Infectious Disease | Galveston, Texas | USA |
| University of Virginia - Acute Care Surgery | Charlottesville, Virginia | USA |
| Universitätsklinikum Frankfurt -Medizinische Klinik II - Infektiologie | Frankfurt | Germany |
| VA Palo Alto Health Care System - Infectious Diseases | Palo Alto, California | USA |
| Vanderbilt University Medical Center - Infectious Diseases | Nashville, Tennessee | USA |
| Walter Reed National Military Medical Center | Bethesda, Maryland | USA |
Trial History
| Event Date | Event Type | Comment |
|---|---|---|
| 15 Oct 2023 | Results | Results of pooled analysis assessing hepatic safety of remdesivir across PINETREE, ACTT-1, and REDPINE presented at the IDWeek 2023. Updated 02 Feb 2024 |
| 19 Jul 2023 | Results | Results published in the Journal of Infectious Diseases Updated 28 Jul 2023 |
| 29 Nov 2022 | Results | Results post hoc of analysis compared recovery and mortality between these comparable sequential cohorts of patients who received remdesivir plus SOC, adjusting for baseline characteristics with propensity score weighting published in the Annals of Internal Medicine Updated 01 Dec 2022 |
| 23 Oct 2022 | Results | Results (n=1048) assessing the SARS-CoV-2 resistance analyses of Remdesivir in hospitalized adults from the Phase 3 ACTT-1 placebo-controlled clinical trial in hospitalized adults, presented at the IDWeek 2022. Updated 02 Feb 2023 |
| 23 Oct 2022 | Results | Results (n=642) assessing virological and immunological biomarkers in RDV-treated patients with moderate/severe disease , presented at the IDWeek 2022 Updated 31 Jan 2023 |
| 10 Oct 2022 | Other trial event | Last checked against ISRCTN record. Updated 10 Oct 2022 |
| 15 Mar 2022 | Other trial event | Last checked against ClinicalTrials.gov record. Updated 15 Mar 2022 |
| 07 Oct 2021 | Other trial event | Last checked against European Clinical Trials Database record. Updated 07 Oct 2021 |
| 19 Aug 2021 | Results | Results(n=1051) assessing the dynamics of clinical progression changed along 4 pathways: recovery, improvement in respiratory therapy requirement, deterioration in respiratory therapy requirement, and death published in the Clinical Infectious Diseases Updated 30 Aug 2021 |
| 11 Aug 2021 | Results | Results of this post-hoc analysis of the adaptive COVID-19 treatment trial-1 cohort data published in the Clinical Infectious Diseases Updated 26 Aug 2021 |
| 12 Jan 2021 | Results | Results (n=19) of a sub-study; serum specimens were obtained from hospitalized adults with COVID-19 randomized to Remdesivir or placebo from this trial assessing antibody and cytokine responses published in the Journal of Infectious Diseases Updated 01 Feb 2021 |
| 23 Nov 2020 | Other trial event | According to a Montefiore Health System and Albert Einstein College of Medicine media release, Dr. Zingman was the principal investigator at Montefiore and Einstein for the ACTT-1 and ACTT-2 National Institutes of Health trials Updated 08 Dec 2020 |
| 22 Oct 2020 | Results | Additional mortality data from a post-hoc analysis were published in the New England Journal of Medicine, according to a Gilead Sciences media release. Updated 27 Oct 2020 |
| 22 Oct 2020 | Other trial event | According to a Gilead Sciences media release, the U.S. Food and Drug Administration (FDA) has approved Veklury (remdesivir) for the treatment of patients with COVID-19 requiring hospitalization, based on data from ACTT-1 and SIMPLE-Severe studies. Updated 27 Oct 2020 |
| 08 Oct 2020 | Endpoint met | Primary endpoint (Time to recovery) has been met. Updated 14 Oct 2020 |
| 08 Oct 2020 | Results | Results published in Gilead Sciences Media Release. Updated 14 Oct 2020 |
| 08 Oct 2020 | Other trial event | According to a Gilead Sciences media release, the European Commission granted conditional marketing authorization of Veklury on July 3, 2020, based on data from this trial. Updated 13 Oct 2020 |
| 14 Sep 2020 | Other trial event | According to a Eli Lilly and Company media release, Andre Kalil, M.D., professor at the University of Nebraska Medical Center and a principal investigator of the ACTT studies. Updated 16 Sep 2020 |
| 28 Aug 2020 | Other trial event | According to a Gilead Sciences media release, based on the SIMPLE-moderate (Study GS-US-540-5774) and ACTT-1 studies, the USA Food and Drug Administration (FDA) has expanded the Emergency Use Authorization (EUA) use of the investigational antiviral Veklury (remdesivir) to treat all hospitalized patients with COVID-19, in addition to the previous authorization for patients hospitalized with severe COVID-19. Updated 02 Sep 2020 |
| 10 Aug 2020 | Other trial event | According to an Gilead Sciences media release, it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Veklury (remdesivir), an investigational antiviral for the treatment of patients with COVID-19.The filing is supported by data from ACTT and SIMPLE Updated 12 Aug 2020 |
| 06 Aug 2020 | Other trial event | According to a National Institutes of Health media release, more detailed information about the results from this study, including more comprehensive data, will be available in a forthcoming report. Updated 17 Aug 2020 |
| 27 Jul 2020 | Other trial event | New source identified and integrated (ISRCTN: Current Controlled Trials :13035264 ). Updated 27 Jul 2020 |
| 14 Jul 2020 | Other trial event | According to a FHI Clinical Inc media release, the company announced that it has a subcontract with the Frederick National Laboratory for Cancer Research, currently operated by Leidos Biomedical Research, Inc., to provide clinical operations services for this study. Updated 16 Jul 2020 |
| 12 Jul 2020 | Interim results | Preliminary results assessing time to recovery in adults hospitalized with COVID-19 and lower respiratory tract involvement treated with remdesivir, published in the Annals of Internal Medicine Updated 27 Jul 2020 |
| 07 Jul 2020 | Status change - completed | Status changed from recruiting to completed. Updated 09 Jul 2020 |
| 25 Jun 2020 | Other trial event | According to an European Medicines Agency media release, based on the data from this trial plus supporting data from other studies on remdesivir, EMA's human medicines committee (CHMP) has recommended granting a conditional marketing authorisation to Veklury (remdesivir) for the treatment of COVID-19 in adults and adolescents from 12 years of age with pneumonia who require supplemental oxygen. Updated 30 Jun 2020 |
| 24 Jun 2020 | Other trial event | Planned number of patients changed from 800 to 1032. Updated 24 Jun 2020 |
| 08 Jun 2020 | Other trial event | According to a European Medicines Agency media releas, EMA has received an application for conditional marketing authorisation of the remdesivir for the treatment of COVID-19 and has started its evaluation. The assessment of the benefits and risks of remdesivir is being performed under a reduced timeline and an opinion could be issued within weeks, depending on the robustness of the data submitted and whether further information is required to support the evaluation. Updated 15 Jun 2020 |
| 26 May 2020 | Other trial event | According to an Emmes media release, the company continues to support the adaptive-design of this study its second stage, in which subjects will be treated with remdesivir and randomized to receive the anti-inflammatory drug baricitinib. Updated 28 May 2020 |
| 22 May 2020 | Interim results | Interim Results published in the New England Journal of Medicine Updated 26 May 2020 |
| 18 May 2020 | Other trial event | According to an Enzychem Lifesciences media release, Dr. Cameron Wolfe is an investigator for this study. Updated 22 May 2020 |
| 11 May 2020 | Other trial event | According to an Emalex Biosciences media release, patients who receive a 5-day treatment course but do not show clinical improvement will be eligible to continue receiving remdesivir. Updated 18 May 2020 |
| 11 May 2020 | Other trial event | According to an Emalex Biosciences media release, a treatment duration of 5 days has been introduced alongside the longer 10-day course, based on preliminary results from another study (GS-US-540-5773) suggesting that for patients not requiring mechanical ventilation or ECMO, the treatment course may be shortened from 10 to 5 days without any loss of efficacy. Updated 18 May 2020 |
| 11 May 2020 | Other trial event | According to an Emalex Biosciences media release, although remdesivir is not yet authorised for marketing in the European Union, these recommendations for compassionate use will help some patients with severe COVID-19 access the medicine while EMA evaluates data on its benefits and risks. When the evaluation is complete, EMA will make a recommendation on whether or not remdesivir should receive a marketing authorisation. Updated 18 May 2020 |
| 11 May 2020 | Other trial event | According to an Emalex Biosciences media release, the updated recommendations are based on preliminary results from the NIAID-ACTT study, which suggest a beneficial effect of remdesivir in the treatment of hospitalised patients with severe COVID-19.EMA is currently evaluating these data in the context of the rolling review of remdesivir. Updated 18 May 2020 |
| 11 May 2020 | Other trial event | According to an Emalex Biosciences media release, in addition to patients undergoing invasive mechanical ventilation, the compassionate use recommendations now cover the treatment of hospitalised patients requiring supplemental oxygen, non-invasive ventilation, high-flow oxygen devices or ECMO (extracorporeal membrane oxygenation). Updated 18 May 2020 |
| 11 May 2020 | Other trial event | According to an Emalex Biosciences media release, EMAs human medicines committee (CHMP) has recommended expanding the compassionate use of the investigational medicine remdesivir so that more patients with severe COVID-19 can be treated. Updated 18 May 2020 |
| 07 May 2020 | Other trial event | According to an Gilead Sciences media release, the Japanese Ministry of Health, Labour and Welfare (MHLW) has granted regulatory approval of Veklury (remdesivir) as a treatment for SARS-CoV-2 infection under an exceptional approval pathway. The exceptional approval was granted due to the COVID-19 pandemic and references the Emergency Use Authorization of remdesivir in the United States. Updated 12 May 2020 |
| 07 May 2020 | Other trial event | According to an Gilead Sciences media release, the Japanese Ministry of Health, Labour and Welfare (MHLW) approval is based on clinical data from the U.S. National Institute of Allergy and Infectious Diseases's global Phase 3 trial, the company's Phase 3 SIMPLE trial in patients with severe manifestations of COVID-19, and available data from company's compassionate use program, including patients in Japan. Updated 12 May 2020 |
| 04 May 2020 | Other trial event | According to an Gilead Sciences media release, data from this study will be reviewed by CHMP as a part of rolling review. Updated 06 May 2020 |
| 01 May 2020 | Other trial event | According to a Gilead Sciences media release, the EUA is based on available data from two global clinical trials, the National Institute for Allergy and Infectious Diseases placebo-controlled Phase 3 study in patients with moderate to severe symptoms of COVID-19 (NCT04280705), including those who were critically ill, and Gileads global Phase 3 study evaluating 5-day and 10-day dosing durations of remdesivir in patients with severe disease (NCT04292899). Updated 08 May 2020 |
| 01 May 2020 | Other trial event | According to a Gilead Sciences media release, the EUA is temporary and does not take the place of the formal new drug application submission, review and approval process. The EUA allows for the distribution and emergency use of remdesivir only for the treatment of COVID-19, remdesivir remains an investigational drug and has not been approved by FDA. Updated 08 May 2020 |
| 01 May 2020 | Other trial event | According to a Gilead Sciences media release, the U.S. FDA has granted emergency use authorization (EUA) for the investigational antiviral remdesivir to treat COVID-19. The EUA will facilitate broader use of remdesivir to treat hospitalized patients with severe COVID-19 disease, enabling access to remdesivir at additional hospitals across the country. Under the EUA, both 5-day and 10-day treatment durations are suggested, based on the severity of disease. Updated 08 May 2020 |
| 30 Apr 2020 | Other trial event | According to an EvergreenHealth media release, Dr. Diego Lopez de Castilla, EvergreenHealth infectious disease specialist is a lead investigator of the study. Updated 05 May 2020 |
| 30 Apr 2020 | Results | Results (n=1063) presented in an EvergreenHealth media release. Updated 05 May 2020 |
| 30 Apr 2020 | Other trial event | According to an EvergreenHealth media release, the institute is preparing to move forward the study by entering into the second arm of the study. The second phase of the trial, ACTT II, will eliminate the placebo group, and instead provide all study participants with Remdesivir. All the patients from the EvergreenHealth's care will receive an open-label Remdesivir. The ACTT II is expected to run for three years. Updated 05 May 2020 |
| 29 Apr 2020 | Other trial event | According to an Gilead Sciences media release, NIAID will provide detailed information at an upcoming briefing Updated 07 May 2020 |
| 29 Apr 2020 | Endpoint met | Primary endpoint has been met. (Time to recovery) Updated 07 May 2020 |
| 23 Apr 2020 | Other trial event | Planned number of patients changed from 572 to 800. Updated 29 Apr 2020 |
| 16 Apr 2020 | Protocol amendment | Primary endpoint has been changed from "Percentage of subjects reporting each severity rating on an 8-point ordinal scale" to Time to recovery. Updated 21 Apr 2020 |
| 16 Apr 2020 | Other trial event | Planned number of patients changed from 440 to 572. Updated 21 Apr 2020 |
| 10 Apr 2020 | Other trial event | According to an Gilead Sciences media release, this study continues to enroll patients and data are anticipated in May 2020. Updated 16 Apr 2020 |
| 30 Mar 2020 | Other trial event | New source identified and integrated:European Clinical Trials Database;EudraCT2020-001052-18. Updated 30 Mar 2020 |
| 24 Mar 2020 | Other trial event | According to an UC San Dieg media release,The trial is projected to run to April 1, 2023 and will ultimately involve an estimated total of 440 participants. It is sponsored by the National Institute of Allergy and Infectious Disease, part of the National Institutes of Health (NIH). Updated 07 May 2020 |
| 24 Mar 2020 | Other trial event | According to an UC San Dieg media release, Constance Benson, M.D., professor of medicine at UC San Diego School of Medicine and an infectious disease specialist at UC San Diego Health.o health media release is co-principal investigator of this study and this study sponsored by the National Institute of Allergy and Infectious Disease, part of the National Institutes of Health (NIH). Updated 07 May 2020 |
| 21 Mar 2020 | Other trial event | According to a U.S. Department of Health and Human Services media release, the US Department of Health and Human Services id funding this trial. Updated 26 Mar 2020 |
| 20 Mar 2020 | Protocol amendment | Phase has been changed from phase II to phase III. Updated 26 Mar 2020 |
| 20 Mar 2020 | Other trial event | Planned number of patients changed from 394 to 440. Updated 26 Mar 2020 |
| 25 Feb 2020 | Other trial event | According to a National Institute of Allergy and Infectious Diseases media release, the first participant is an American who was repatriated after being quarantined on the Diamond Princess cruise ship that docked in Yokohama, Japan and volunteered to participate in the study. Updated 27 Feb 2020 |
| 25 Feb 2020 | Status change - recruiting | Status changed from not yet recruiting to recruiting, according to a National Institute of Allergy and Infectious Diseases media release. Updated 27 Feb 2020 |
| 24 Feb 2020 | New trial record | New trial record Updated 24 Feb 2020 |
Table of Contents
References
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Gilead Sciences. Final Results of National Institute of Allergy and Infectious Diseases ACTT-1 Trial Published in New England Journal of Medicine Expand Clinical Benefits of Veklury(Rm) (remdesivir) for the Treatment of COVID-19. Media-Rel 2020;.
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Gilead Sciences. U.S. Food and Drug Administration Approves Gileads Antiviral Veklury(Rm) (remdesivir) for Treatment of COVID-19. Media-Rel 2020;.
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European Medicines Agency. First COVID-19 treatment recommended for EU authorisation . Media-Rel 2020;.
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EvergreenHealth. EvergreenHealth Prepares for Second Arm of Clinical Trial After Initial Findings Show Promising Results for Remdesivir as Potential Treatment for COVID-19. Media-Rel 2020;.
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