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.

At a glance

Drugs Remdesivir (Primary)
Indications COVID 2019 infections
Focus Registrational; Therapeutic Use

Most Recent Events

22 Dec 2020 Data from this and other study (NCT03652363) was used to demonstrate the use of two plots identified to be beneficial for wide use in RCTs, Results published in the Trials.
24 May 2020 Results published in the Trials.
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.

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

Drug Name	Highest Phase	Originator
Remdesivir - Gilead Sciences	Marketed	Gilead Sciences
Remdesivir oral - Vivtex Corporation	Preclinical	Vivtex Corporation
Remdesivir controlled release - Starpharma	Research	Starpharma

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

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
Cornelius V, Cro S, Phillips R. Advantages of visualisations to evaluate and communicate adverse event information in randomised controlled trials. Trials 2020;21(1):1028.
PubMed | CrossRef Fulltext
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/
Wang Y, Zhou F, Zhang D, Zhao J, Du R, Hu Y, et al. Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial. Trials 2020;21(1):422.
PubMed | CrossRef Fulltext

Authors

Author	Total Publications	First Author	Last Author
Bailes Z	1	-	-
Barnes N	1	-	-
Cao B	1	-	-
Cheng Z	1	-	-
Cornelius V	1	1	-
Cro S	1	-	-
Dingyu Zhang MD	1	-	1
Du G	1	-	-
Du R	1	-	-
Edwards D	1	-	-
Fan G	1	-	-
Fowler Ad	1	-	-
Fu S	1	-	-
Gao L	1	-	-
Gardiner F	1	-	-
Hanania N	1	1	-
Hayden FG	1	-	-
Horby PW	1	-	-
Hu Y	1	-	-
Jaki T	1	-	-
Jin Y	1	-	-
Kerstjens H	1	-	-
Kerwin E	1	-	-
Lee L	1	-	1
Liu W	1	-	-
Liu Y	1	-	-
Lu Q	1	-	-
Lu Y	1	-	-
Luo G	1	-	-
Pascoe S	1	-	-
Pavord I	1	-	-
Peachey G	1	-	-
Phillips R	1	-	1
Ruan S	1	-	-
Sule N	1	-	-
Wang C	1	-	1
Wang K	1	-	-
Wang Y	1	1	-
Yeming Wang MD	1	1	-
Zhang D	1	-	-
Zhang Y	1	-	-
Zhao J	1	-	-
Zhou F	1	-	-

Trial Centres

Investigators

Download Data (CSV)

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

Centres

Download Data (CSV)

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

Trial History

Event Date	Event Type	Comment
22 Dec 2020	Results	Data from this and other study (NCT03652363) was used to demonstrate the use of two plots identified to be beneficial for wide use in RCTs, Results published in the Trials. Updated 19 Jan 2021
24 May 2020	Results	Results published in the Trials. Updated 11 Jun 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
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. ClinicalTrials.gov: US National Institutes of Health 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. ClinicalTrials.gov: US National Institutes of Health Updated 25 Feb 2020
14 Feb 2020	New trial record	New trial record ClinicalTrials.gov: US National Institutes of Health Updated 14 Feb 2020

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