Coronavirus disease 2019 (COVID-19) in patients who have a high risk of developing serious or severe illness MedDRA version: 23.0 Level: PT Classification code 10051905 Term: Coronavirus infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Obeldesivir
Product Code: GS-5245
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Obeldesivir
CAS Number: 2647441-36-7
Current Sponsor code: GS-5245
Other descriptive name:
Sponsors
Gilead Sciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants must meet all the following inclusion criteria to be eligible for participation in this study: 1) Aged = 18 years at screening. 2) Willing and able to provide written informed consent, or with a legal representative who can provide informed consent (where locally and nationally approved). 3) SARS-CoV-2 infection confirmed by PCR or an alternative approved assay locally approved (eg, Rapid Antigen Test) = 5 days before randomization. Serologic tests will not be accepted. 4) Initial onset of COVID-19 signs/symptoms = 5 days before randomization with = 1 of the following targeted signs/symptoms present at randomization. a. Stuffy or runny nose. b. Sore throat. c. Shortness of breath (difficulty breathing). d. Cough. e. Low energy or tiredness. f. Muscle or body aches. g. Headache. h. Chills or shivering. i. Feeling hot or feverish. j. Nausea. k. Vomiting. l. Diarrhoea. 5) Not currently hospitalized or requiring hospitalization. 6) Presence of = 1 risk factor (if unvaccinated) or = 2 risk factors (if vaccinated at any point) for progression to severe disease. Risk factors are the following: a. Aged = 50 years. b. Current or recent (= 6 months prior to randomization) cancer (other than localized skin cancer). c. Have human immunodeficiency virus infection. d. Prior splenectomy. e. Prior solid organ, stem cell, or bone marrow transplant. f. Have systemic rheumatologic or dermatologic disorders. g. Use of systemic immunosuppressive agents, eg, high-dose corticosteroids (ie, =20 mg of prednisone or equivalent per day administered for =2 weeks), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, tumor necrosis factor (TNF) blockers, other biologic agents that are immunosuppressive or immunomodulatory. h. Have cerebrovascular disease. i. Have cardiovascular disease, including heart failure, coronary artery disease, cardiomyopathies, and hypertension. j. Have chronic kidney disease (provided participant does not meet exclusion criteria 7). k. Have chronic lung disease (including interstitial lung disease, pulmonary embolism, pulmonary hypertension, bronchiectasis, or chronic obstructive pulmonary disease). l. Have chronic liver disease. m. Have cystic fibrosis. n. Have diabetes mellitus, type 1 and/or type 2. o. Have neurodevelopmental and/or neurodegenerative conditions. p. Have a body mass index = 25 kg/m2. q. Have sickle cell disease. r. Have primary immunodeficiencies. s. Have compensated cirrhosis. t. Have asthma. u. Have = 20 pack-year smoking history and currently smoking or have quit within the past 15 years. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 2520 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 630
Exclusion criteria
Exclusion criteria: Exclusion criteria for participation include: 1) Anticipated access to and use of authorized or approved COVID-19 therapies during the current COVID-19 illness < 5 days after randomization (therapies include nirmatrelvir/ritonavir, molnupiravir, ensitrelvir, IV RDV, monoclonal antibodies). 2) Received any approved, authorized, or investigational direct acting antiviral drug against SARS-CoV-2 for the treatment of COVID-19 < 28 days or < 5 half-lives, whichever is longer, before randomization. 3) Anticipated need for hospitalization < 48 hours after randomization. 4) New oxygen requirement < 24 hours before randomization. 5) Known influenza or any other suspected or confirmed concurrent active systemic infection other than COVID-19 that may interfere with the valuation of response to the study drug. 6) Decompensated cirrhosis (Child-Pugh class B or class C) or acute liver injury/failure. 7) Undergoing dialysis, or known history of moderate or severe renal impairment or known CLcr < 60 mL/min (as calculated by Cockroft-Gault) or eGFR < 60 mL/min/1.73m2 within the last 6 months. Potential participants meeting the laboratory criterion may be enrolled if test results available before dosing show that renal function no longer meets this criterion. See Appendix 11.4 for country-specific requirements. 8) Known history of any of the following abnormal laboratory results (< 6 months before randomization) unless confirmed as resolved to not meet criteria at screening. See Appendix 11.4 for country-specific requirements regarding these laboratory exclusions. a. ALT = 5 x ULN. b. Bilirubin = 2 x ULN (= 3 x ULN for participants with Gilbert’s syndrome). 9) Positive urine pregnancy test at screening. 10) Breastfeeding (nursing). 11) Unwilling to use protocol-mandated birth control. 12) Known hypersensitivity to the study drug, its metabolites, or formulation excipient. 13) Requirement for ongoing therapy with or prior use of any prohibited medications. Prohibited medications are identified in Section 5.4.1. 14) Received an approved, authorized, or investigational COVID-19 vaccine (including booster dose) < 120 days before randomization. 15) Any inability to take study drug or comply with study procedures that, in the opinion of the investigator, would make the participant unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the efficacy of GS-5245 in reducing the rate of COVID-19–related hospitalization or all-cause death;Secondary Objective: Secondary Objectives: •To evaluate the safety and tolerability of GS-5245 administered in nonhospitalized participants with COVID-19 •To evaluate the efficacy of GS-5245 in reducing all-cause hospitalization •To evaluate the efficacy of GS-5245 in reducing COVID-19–related medically attended visits (MAVs) or all-cause death •To evaluate the efficacy of GS-5245 in reducing COVID-19–related MAVs •To evaluate the efficacy of GS-5245 in reducing COVID-19–related all-cause death •To evaluate the efficacy of GS-5245 in reducing the duration and severity of COVID-19 symptoms •To evaluate the antiviral activity of GS-5245 on SARS-CoV-2 nasal swab viral load at Day 5 •To evaluate the plasma PK of GS-441524 (metabolite of GS-5245) Exploratory Objective: See Protocol Section 2 ;Primary end point(s): •Proportion of COVID-19-related hospitalization or all-cause death by Day 29;Timepoint(s) of evaluation of this end point: At various timepoints throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints: • Incidence of treatment-emergent AEs and laboratory abnormalities • Incidence of SAEs and AEs leading to study drug discontinuation • Proportion of participants with all cause hospitalization by Day 29 • Proportion of participants with COVID-19-related MAVs or all-cause death by Day 29 • Proportion of participants with COVID-19-related MAVs by Day 29 • Proportion of participants with all-cause death by Day 29 • Time to COVID-19 symptom alleviation by Day 15 • Change from baseline (Day 1) in SARS-CoV-2 nasal swab viral load at Day 5 • Plasma concentrations and PK parameters AUCtau, Ctau, and Cmax of GS-441524, as available. Exploratory Endpoint(s): See Section 2 of the amended Protocol.;Timepoint(s) of evaluation of this end point: At various timepoints throughout the study | — |
Countries
Argentina, Brazil, Bulgaria, Canada, Colombia, Czechia, France, Hungary, India, Italy, Japan, Kenya, Korea, Republic of, Mexico, Philippines, Poland, Portugal, Romania, Singapore, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, United Kingdom
Contacts
Public ContactClinical Trials Mailbox
Gilead Sciences International Ltd.
Outcome results
None listed