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A Phase 3 Randomized Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734) in Participants with Severe COVID-19

A Phase 3 Randomized Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734) in Participants with Severe COVID-19

401

Demographic and baseline characteristics were similar between the 2 treatment groups. The majority of the participants were male (63.7%). The median age was 61 years (range 20 to 98 years); the majority of participants were white (75.0%) and were not Hispanic/Latino (78.0%). The median (first quartile [Q1], third quartile [Q3]) body mass index was 28.7 (25.3, 33.5) kg/m2.

Of the 397 participants treated in Part A, 35.0% (139 participants) prematurely discontinued study treatment (remdesivir 5-day group 14.0%, 28 participants; remdesivir 10-day group 56.3%, 111 participants), and 16.4% (65 participants) prematurely discontinued from the study (remdesivir 5-day group 16.0%, 32 participants; remdesivir 10-day group 16.8%, 33 participants). The most common reasons for premature discontinuation of study treatment were hospital discharge (remdesivir 5-day group 8.0%, 16 participants; remdesivir 10-day group 34.0%, 67 participants), AE (remdesivir 5-day group 4.5%, 9 participants; remdesivir 10-day group 11.2%, 22 participants), and death (remdesivir 5-day group 0 participants; remdesivir 10-day group 6.1%, 12 participants).

Similar percentages of participants in remdesivir 5-day and remdesivir 10-day groups had AEs during the study (71.5% and 75.1%, respectively). Through Day 5, Grade 3 or higher AEs and serious adverse events (SAEs) were reported in lower percentages of participants in the remdesivir 5-day group than the remdesivir 10-day group. When categorized by oxygen support status at Day 5, the percentage of participants with overall AEs occurring on or after Day 6 was similar between the groups. Participants who were older (>= 65 years) generally had higher percentages of AEs than those who were younger (< 65 years), and higher incidences of deaths, SAEs, and severe (Grade 3 or higher) AEs were reported in participants who were older, male, or at sites in Italy versus the USA or outside Italy. The 3 most commonly reported AEs for each treatment group were as follows: - Remdesivir 5-day group: nausea (10.0%, 20 of 200 participants), constipation (6.5%, 13 participants), and acute respiratory failure (6.0%, 12 participants) - Remdesivir 10-day group: acute respiratory failure (10.7%, 21 of 197 participants), nausea (8.6%, 17 participants), and acute kidney injury (8.1%, 16 participants)

The primary efficacy endpoint for the study was clinical status assessed using a 7-point ordinal scale on Day 14 in the overall study population. Primary analysis of the primary endpoint demonstrated that treatment with remdesivir for 5 days and treatment with remdesivir for 10 days resulted in similar odds of improved clinical status at Day 14 (p = 0.1563).

Other endpoints of interest evaluated during the study included oxygen support status, duration of hospitalization, mortality, clinical improvement, recovery, and time to room air. There were no statistically significant differences between the remdesivir 5-day and 10-day treatment groups in the number of days of oxygen support at any level in participants who were discharged alive or who died on or before Day 14, and no notable differences between treatment groups in shift in oxygen support status from baseline.

- Remdesivir administered for 5 days or 10 days to participants with severe COVID-19 resulted in similar improvements in clinical status at Day 14, as assessed by a 7-point ordinal scale, after adjustment for imbalances in baseline clinical status. - Patients on invasive mechanical ventilation may benefit from a treatment duration longer than 5 days. - Remdesivir administered for 5 days or 10 days was generally safe and well tolerated in participants with severe COVID-19.

May. 27, 2020

https://www.nejm.org/doi/full/10.1056/nejmoa2015301

No

-

https://www.clinicaltrials.jp/file/THmOjUZed

Gilead Sciences, K.K.

1-9-2, Marunouchi, Chiyoda-ku, Tokyo

Gilead Sciences, K.K.

1-9-2, Marunouchi, Chiyoda-ku, Tokyo

JPClinicalOperations@gilead.com

completed

April. 16, 2020

Interventional

Randomized, Treatment

treatment purpose

3

-Willing and able to provide written informed consent, or with a legal representative who can provide informed consent, or enrolled under ICH E6(R2)4.8.15 emergency use provisions as deemed necessary by the investigator (participants >= 18 years of age), or willing and able to provide assent (participants >= 12 and < 18 years of age, where locally and nationally approved) prior to performing study procedures. For participants >= 12 and < 18 years of age,a parent or legal guardian willing and able to provide written informed consent prior to performing study procedures
-Aged >= 18 years (at all sites), or aged >= 12 and < 18 years of age weighing >= 40kg (where permitted according to local law and approved nationally and by the relevant institutional review board(IRB) or independent ethics committee (IEC))
-SARS-CoV-2 infection confirmed by PCR test =< 4 days before randomization
-Currently hospitalized
-SpO2 =< 94% on room air or requiring supplemental oxygen at screening
-Radiographic evidence of pulmonary infiltrates

-Participation in any other clinical trial of an experimental treatment for COVID-19
-Concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 < 24 hours prior to study drug dosing
-Evidence of multiorgan failure
-Mechanically ventilated(including V-V ECMO) >= 5 days,or any duration of V-A ECMO
-ALT or AST > 5 X ULN
-Creatinine clearance < 50 mL/min using the Cockcroft-Gault formula for participants >= 18 years of age (Cockcroft 1976) and Schwartz Formula for participants < 18 years of age

Both

COVID-19-Infection

investigational material(s)
Generic name etc : Remdesivir
INN of investigational material : remdesivir
Therapeutic category code : 625 Anti-virus agents
Dosage and Administration for Investigational material : Treatment Group 1:continued SOC therapy together with IV Remdesivir(RDV)200mg on Day 1 followed by IV RDV 100mg on Days 2,3,4,and 5
Treatment Group 2:continued SOC therapy together with IV RDV 200mg on Day1 followed by IV RDV 100mg on Days 2,3,4,5,6,7,8,9, and 10
In Part B, participants who meet all of the eligibility criteria will be enrolled,based on whether they are mechanically ventilated at enrollment, to receive
Mechanically Ventilated Treatment Group:continued standard of care therapy together with IV RDV 200mg on Day1 followed by IV RDV 100mg on Days 2,3,4,5,6,7,8,9, and 10
Extension Treatment Group:continued standard of care therapy together with IV RDV 200mg on Day1 followed by IV RDV 100mg on Days 2,3,4,5,6,7,8,9, and 10

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : -

efficacy
Clinical status assessed by a 7-point ordinal scale on Day 14

safety
Proportion of Participants With Treatment Emergent Adverse Events Leading to Study Drug Discontinuation

April. 09, 2020