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A Phase 3 Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir in Hospitalized Adult Patients With Severe COVID-19.

Trial Profile

A Phase 3 Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir in Hospitalized Adult Patients With Severe COVID-19.

Status: Discontinued
Phase of Trial: Phase III

Latest Information Update: 04 May 2020

At a glance

  • Drugs Remdesivir (Primary)
  • Indications COVID 2019 infections
  • Focus Registrational; Therapeutic Use
  • Most Recent Events

    • 04 May 2020 According to an Gilead Sciences media release, data from this study will be reviewed by CHMP as a part of rolling review.
    • 29 Apr 2020 Primary endpoint (Time to Clinical Improvement (TTCI)) has not been met.
    • 29 Apr 2020 Results published in the Lancet.

Trial Overview

Outcome

Primary endpoint not met - negative

Purpose

In December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia of unknown cause. In a short time, Chinese scientists had shared the genome information of a novel coronavirus (SARS-CoV-2) from these pneumonia patients and developed a real-time reverse transcription PCR (real-time RT-PCR) diagnostic assay. Given no specific antiviral therapy for COVID-19 and the ready availability of remdesvir as a potential antiviral agent, based on pre-clinical studies in SARS-CoV and MERS-CoV infections, this randomized, controlled, double blind trial will evaluate the efficacy and safety of remdesivir in patients hospitalized with severe COVID-19.

Comments

According to an Gilead Sciences media release, data from this study will be reviewed by CHMP as a part of rolling review.

According to an Gilead Sciences media release, this study in patients with severe disease was terminated early due to low enrollment.

According to Clinicaltrials.gov, trial was terminated due to the epidemic of COVID-19 which has been controlled well in China, no eligible patients can be enrolled at present.

Primary Endpoints

Not met, 29 Apr 2020

Time to Clinical Improvement (TTCI) [Censored at Day 28]

description: The primary endpoint is time to clinical improvement (censored at Day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 discharged; 6 death) or live discharge from hospital.
Six-category ordinal scale:
6. Death; 5. ICU, requiring ECMO and/or IMV; 4. ICU/hospitalization, requiring NIV/ HFNC therapy; 3. Hospitalization, requiring supplemental oxygen (but not NIV/ HFNC); 2. Hospitalization, not requiring supplemental oxygen;
1. Hospital discharge or meet discharge criteria (discharge criteria are defined as clinical recovery, i.e. fever, respiratory rate, oxygen saturation return to normal, and cough relief).
Abbreviation: IMV, invasive mechanical ventilation; NIV, non-invasive mechanical ventilation; HFNC, High-flow nasal cannula.
time_frame: up to 28 days [1]

Other Endpoints

Clinical status

description: Clinical status, assessed by the ordinal scale at fixed time points (days 7, 14, 21, and 28).
time_frame: days 7, 14, 21, and 28

Time to Hospital Discharge OR NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours.

description: Time to Hospital Discharge OR NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours.
time_frame: up to 28 days

All cause mortality

time_frame: up to 28 days

Duration (days) of mechanical ventilation

time_frame: up to 28 days

Duration (days) of extracorporeal membrane oxygenation

time_frame: up to 28 days

Duration (days) of supplemental oxygenation

time_frame: up to 28 days

Length of hospital stay (days)

time_frame: up to 28 days

Time to 2019-nCoV RT-PCR negativity in upper and lower respiratory tract specimens

time_frame: up to 28 days

Change (reduction) in 2019-nCoV viral load in upper and lower respiratory tract specimens as assessed by area under viral load curve.

time_frame: up to 28 days

Frequency of serious adverse drug events

time_frame: up to 28 days [2]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 453

    Actual: 237

  • Sex male & female
  • Age Group ≥ 18 years; adult

Patient Inclusion Criteria

1. Age ≥18 years at time of signing Informed Consent Form 2. Laboratory (RT-PCR) confirmed COVID-19. 3. Lung involvement confirmed with chest imaging 4. Hospitalized with a SaO2/SPO2≤94% on room air or Pa02/Fi02 ratio <300mgHg 5. ≤12 days since illness onset 6. Willingness of study participant to accept randomization to any assigned treatment arm. 7. Must agree not to enroll in another study of an investigational agent prior to completion of Day 28 of study.

Patient Exclusion Criteria

1. Physician makes a decision that trial involvement is not in patients' best interest, or any condition that does not allow the protocol to be followed safely. 2. Severe liver disease (e.g. Child Pugh score ≥ C, AST>5 times upper limit) 3. Pregnant or breastfeeding, or positive pregnancy test in a predose examination 4. Patients with known severe renal impairment (estimated glomerular filtration rate ≤30 mL/min/1.73 m2) or receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis 5. Will be transferred to another hospital which is not the study site within 72 hours. 6. Receipt of any experimental treatment for COVID-19 within the 30 days prior to the time of the screening evaluation.

Trial Details

Identifiers

Identifier Owner
NCT04257656 ClinicalTrials.gov: US National Institutes of Health
CAP-China-remdesivir2 -

Trial Dates

  • Initiation Dates

    Actual : 06 Feb 2020

  • Primary Completion Dates

    Planned : 03 Apr 2020

    Actual : 30 Mar 2020

  • End Dates

    Planned : 01 May 2020

    Actual : 10 Apr 2020

Other Details

  • Design double-blind; multicentre; parallel; prospective; randomised
  • Phase of Trial Phase III
  • Location China
  • Focus Registrational; Therapeutic Use

Interventions

Drugs Route Formulation
RemdesivirPrimary Drug Intravenous Infusion

Remdesivir group

active remdesivir
Drug: Remdesivir (RDV 200 mg loading dose on day 1 is given, followed by 100 mg iv once-daily maintenance doses for 9 days.) Other Name: GS-5734

Control group

Placebos matched remdesivir
Drug: Remdesivir placebo (RDV placebo 200 mg loading dose on day 1 is given, followed by 100 mg iv once-daily maintenance doses for 9 days.)

Results

Publications

  1. Yeming Wang MD, Dingyu Zhang MD. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Internet-Doc 2020;.

    Available from: URL: http://link.adisinsight.com/Lx62F
  2. Hanania N, Kerwin E, Pavord I, Kerstjens H, Pascoe S, Peachey G, et al. Step-up to high dose fluticasone furoate in combination with long-acting bronchodilator in inadequately controlled asthma: the CAPTAIN study. AAAAI-2020 2020; abstr. 072.

    Available from: URL: http://annualmeeting.aaaai.org/

Authors

Author Total Publications First Author Last Author
Bailes Z 1 - -
Barnes N 1 - -
Dingyu Zhang MD 1 - 1
Edwards D 1 - -
Fowler Ad 1 - -
Gardiner F 1 - -
Hanania N 1 1 -
Kerstjens H 1 - -
Kerwin E 1 - -
Lee L 1 - 1
Pascoe S 1 - -
Pavord I 1 - -
Peachey G 1 - -
Sule N 1 - -
Yeming Wang MD 1 1 -

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Yeming Wang, Doctor
wwyymm_love@163.com
show details
Bin Cao China

Centres

Centre Name Location Trial Centre Country
Bin Cao Beijing, Beijing China
Capital Medical University
-
-

Trial History

Event Date Event Type Comment
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
29 Apr 2020 Endpoint not met Primary endpoint (Time to Clinical Improvement (TTCI)) has not been met. Updated 30 Apr 2020
29 Apr 2020 Results Results published in the Lancet. Updated 30 Apr 2020
16 Apr 2020 Other trial event Last checked against ClinicalTrials.gov record. Updated 16 Apr 2020
10 Apr 2020 Other trial event According to an Gilead Sciences media release, this study in patients with severe disease was terminated early due to low enrollment. The company awaits the publication of these data to enable an in-depth review of the results. Updated 16 Apr 2020
10 Apr 2020 Status change - discontinued Status changed from recruiting to discontinued, according to an Gilead Sciences media release. Updated 16 Apr 2020
16 Mar 2020 Results Results presented at the 2020 Annual Meeting of the American Academy of Allergy, Asthma and Immunology Updated 30 Apr 2020
20 Feb 2020 Other trial event Planned number of patients changed from 452 to 453. Updated 25 Feb 2020
14 Feb 2020 New trial record New trial record Updated 14 Feb 2020

References

  1. Yeming Wang MD, Dingyu Zhang MD. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Internet-Doc 2020;.

    Available from: URL: http://link.adisinsight.com/Lx62F
  2. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
  3. European Medicines Agency. EMA starts rolling review of remdesivir for COVID-19. Media-Rel 2020;.

    Media Release
  4. Hanania N, Kerwin E, Pavord I, Kerstjens H, Pascoe S, Peachey G, et al. Step-up to high dose fluticasone furoate in combination with long-acting bronchodilator in inadequately controlled asthma: the CAPTAIN study. AAAAI-2020 2020; abstr. 072.

    Available from: URL: http://annualmeeting.aaaai.org/
  5. Gilead Sciences. Data on 53 Patients Treated With Investigational Antiviral Remdesivir Through the Compassionate Use Program Published in New England Journal of Medicine. Media-Rel 2020;.

    Media Release
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