Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734™) in Participants With Severe Coronavirus Disease (COVID-19)

• ClinicalTrials.gov Identifier: NCT04292899
• Recruitment Status: Completed
• First Posted: March 3, 2020
• Results First Posted: December 31, 2020
• Last Update Posted: December 31, 2020
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: February 28, 2020
• First Posted Date: March 3, 2020
• Results First Submitted Date: December 15, 2020
• Results First Posted Date: December 31, 2020
• Last Update Posted Date: December 31, 2020
• Actual Study Start Date: March 6, 2020
• Actual Primary Completion Date: April 9, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 15, 2020)

Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 14 [ Time Frame: Day 14 ]

Clinical status was derived from death, hospital discharge, and the ordinal scale as follows: score of "1" was used for all days on or after the date of death; score of "7" was used for all days on or after discharged alive date; last assessment carried forward for any missing values.The scale is as follows: 1. Death; 2. Hospitalized, on invasive mechanical ventilation or ECMO; 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring low flow 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 required ongoing medical care (other than per protocol remdesivir administration); 7. Not hospitalized. The odds ratio represents the odds of improvement in the ordinal scale for the Remdesivir for 10 days group vs the Remdesivir for 5 days group.

Original Primary Outcome Measures (submitted: February 28, 2020)

Proportion of Participants With Normalization of Fever and Oxygen Saturation Through Day 14 [ Time Frame: First dose date up to 14 days ]

This is a composite outcome measure. Criteria for fever normalization: Temperature < 36.6 °C armpit, < 37.2 °C oral, or < 37.8 °C rectal sustained for at least 24 hours and criteria for oxygen normalization: peripheral capillary oxygen saturation (Sp02) > 94% sustained for at least 24 hours.

Current Secondary Outcome Measures (submitted: December 15, 2020)

Part A: Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: First dose date up to last dose date (maximum: 10 days) plus 30 days ]

Treatment-emergent Adverse Events (TEAE) were defined as AEs with onset dates on or after the study treatment start date and no later than 30 days after the permanent discontinuation of the study treatment and/or the AEs that led to premature discontinuation of study treatment.

• Original Secondary Outcome Measures (submitted: February 28, 2020): Proportion of Participants With Treatment Emergent Adverse Events Leading to Study Drug Discontinuation [ Time Frame: First dose date up to 10 days ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734™) in Participants With Severe Coronavirus Disease (COVID-19)
• Official Title: A Phase 3 Randomized Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734™) in Participants With Severe COVID-19
• Brief Summary: The primary objective of this study is to evaluate the efficacy of 2 remdesivir (RDV) regimens with respect to clinical status assessed by a 7-point ordinal scale on Day 14.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: COVID-19

Intervention

• Drug: Remdesivir
  Administered as an intravenous infusion
  Other Names:

  • GS-5734™
  • Veklury®
• Drug: Standard of Care
  Standard of Care Treatment for COVID-19 Infection

Study Arms

• Experimental: Part A: Remdesivir (RDV), 5 Days
  Participants will receive continued standard of care therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg on Days 2, 3, 4, and 5.
  Interventions:

  • Drug: Remdesivir
  • Drug: Standard of Care
• Experimental: Part A: Remdesivir, 10 Days
  Participants will receive continued standard of care therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg on Days 2, 3, 4, 5, 6, 7, 8, 9, and 10.
  Interventions:

  • Drug: Remdesivir
  • Drug: Standard of Care
• Experimental: Part B: Remdesivir, 10 Days (Extension)
  Part B (Extension) will enroll participants after enrollment to Part A is complete. Participants will receive continued standard of care therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg on Days 2-10.
  Interventions:

  • Drug: Remdesivir
  • Drug: Standard of Care
• Experimental: Part B: Remdesivir 10 days (Mechanically Ventilated)
  Participants on mechanical ventilation will receive continued standard of care therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg on Days 2-10
  Interventions:

  • Drug: Remdesivir
  • Drug: Standard of Care

Publications *

• Goldman JD, Lye DCB, Hui DS, Marks KM, Bruno R, Montejano R, Spinner CD, Galli M, Ahn MY, Nahass RG, Chen YS, SenGupta D, Hyland RH, Osinusi AO, Cao H, Blair C, Wei X, Gaggar A, Brainard DM, Towner WJ, Munoz J, Mullane KM, Marty FM, Tashima KT, Diaz G, Subramanian A; GS-US-540-5773 Investigators. Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. N Engl J Med. 2020 Nov 5;383(19):1827-1837. doi: 10.1056/NEJMoa2015301. Epub 2020 May 27.
• Jacobson KB, Rao M, Bonilla H, Subramanian A, Hack I, Madrigal M, Singh U, Jagannathan P, Grant P. Patients With Uncomplicated Coronavirus Disease 2019 (COVID-19) Have Long-Term Persistent Symptoms and Functional Impairment Similar to Patients with Severe COVID-19: A Cautionary Tale During a Global Pandemic. Clin Infect Dis. 2021 Aug 2;73(3):e826-e829. doi: 10.1093/cid/ciab103.
• Olender SA, Perez KK, Go AS, Balani B, Price-Haywood EG, Shah NS, Wang S, Walunas TL, Swaminathan S, Slim J, Chin B, De Wit S, Ali SM, Soriano Viladomiu A, Robinson P, Gottlieb RL, Tsang TYO, Lee IH, Hu H, Haubrich RH, Chokkalingam AP, Lin L, Zhong L, Bekele BN, Mera-Giler R, Phulpin C, Edgar H, Gallant J, Diaz-Cuervo H, Smith LE, Osinusi AO, Brainard DM, Bernardino JI; GS-US-540-5773 and GS-US-540-5807 Investigators. Remdesivir for Severe Coronavirus Disease 2019 (COVID-19) Versus a Cohort Receiving Standard of Care. Clin Infect Dis. 2021 Dec 6;73(11):e4166-e4174. doi: 10.1093/cid/ciaa1041.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 23, 2020): 4891
• Original Estimated Enrollment (submitted: February 28, 2020): 400
• Actual Study Completion Date: June 30, 2020
• Actual Primary Completion Date: April 9, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Willing and able to provide written informed consent, or with a legal representative who can provide informed consent, or enrolled under International Conference on Harmonization (ICH) E6(R2) 4.8.15 emergency use provisions as deemed necessary by the investigator (age ≥ 18), or willing and able to provide assent (age ≥ 12 to < 18, where locally and nationally approved) prior to performing study procedures
• Aged ≥ 18 years (at all sites), or aged ≥ 12 and < 18 years of age weighing ≥ 40 kg (where permitted according to local law and approved nationally and by the relevant institutional review board (IRB) or independent ethics committee (IEC))
• Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test ≤ 4 days before randomization
• Currently hospitalized
• Peripheral capillary oxygen saturation (SpO2) ≤ 94% or requiring supplemental oxygen at screening

Key Exclusion Criteria:

• 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 is prohibited < 24 hours prior to study drug dosing
• Evidence of multiorgan failure
• Mechanically ventilated [including veno-venous (V-V) extracorporeal membrane oxygenation (ECMO)] ≥ 5 days, or any duration of veno-arterial (V-A) ECMO.
• Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 X upper limit of normal (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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Netherlands, Singapore, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT04292899
• Other Study ID Numbers: GS-US-540-5773; 2020-000841-15 ( EudraCT Number ); ISRCTN15874265 ( Other Identifier: ISRCTN )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.
• URL: https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy

• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: December 2020