E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084382 |
E.1.2 | Term | Coronavirus disease 2019 |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To evaluate the efficacy of RDV in reducing the rate of all-cause medically attended visits (MAVs; medical visits attended in person by the participant and a health care professional) or death when given over 3 days to non-hospitalized participants with early stage COVID-19.
- To evaluate the safety of RDV administered in an outpatient setting
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E.2.2 | Secondary objectives of the trial |
- To determine the antiviral activity of RDV on SARS-CoV-2 viral load
- To assess the impact of RDV on symptom duration and severity |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participants must meet all of the following inclusion criteria to be eligible for participation in this
study:
1) Willing and able to provide written informed consent, (participants ≥ 18 years of age) or assent (participants ≥ 12 and < 18 years of age) prior to performing study procedures. Participants aged ≥ 18 years may be enrolled with the consent of a legal representative where permitted according to local law and approved nationally and by the relevant institutional review board (IRB) or independent ethics committee (IEC). For participants ≥ 12 and < 18 years of age, a parent or legal guardian must be willing and able to provide written informed consent prior to performing study procedures
2) Either:
- Age ≥ 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 IRB or IEC) with at least 1 of the following pre-existing risk factors for progression to hospitalization:
a) Chronic lung disease: chronic obstructive pulmonary disease, moderate-to-severe asthma, cystic fibrosis, pulmonary fibrosis
b) Hypertension: systemic or pulmonary
c) Cardiovascular or cerebrovascular disease: coronary artery disease, congenital heart disease, heart failure, cardiomyopathy, history of stroke, atrial fibrillation, hyperlipidemia
d) Diabetes mellitus: Type 1, type 2, or gestational
e) Obesity (BMI ≥ 30)
f) Immunocompromised state; having a solid organ transplant, blood, or bone marrow transplant; immune deficiencies; HIV with a low CD4 cell count or not on HIV treatment; prolonged use of corticosteroids; or use of other immune weakening medicines
g) Chronic mild or moderate kidney disease
h) Chronic liver disease
i) Current cancer
j) Sickle cell disease
- OR aged ≥ 60 years, regardless of the presence of other pre-existing risk factors for progression
3) SARS-CoV-2 infection confirmed by molecular diagnostics (nucleic acid [eg, PCR] or antigen testing) ≤ 4 days prior to screening
4) Presence of ≥ 1 symptom(s) consistent with COVID-19 for ≤ 7 days prior to randomization (such as fever, cough, fatigue, shortness of breath, sore throat, headache, myalgia/arthralgia)
5) Not currently receiving, requiring, or expected to require supplemental oxygen
6) Not currently requiring hospitalization (hospitalization defined as ≥ 24 hours of acute care)
7) Participants of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in Protocol Appendix 3 |
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E.4 | Principal exclusion criteria |
Participants who meet any of the following exclusion criteria are not eligible to be enrolled in this study:
1) Participation in any other clinical trial of an experimental treatment and prevention for COVID-19
2) Prior hospitalization for COVID-19 (hospitalization defined as ≥ 24 hours of acute care)
3) Treatment with other agents with actual or possible direct antiviral activity against SARS-CoV-2
4) Requiring oxygen supplementation
5) ALT or AST ≥ 5 × upper limit of normal (ULN) at screening or within 90 days of screening Note: if per local practice only ALT is routinely measured, exclusion criteria will be evaluated on ALT alone
6) Creatinine clearance < 30 mL/min at screening or within 90 days of screening using the Cockcroft-Gault formula in participants ≥ 18 years of age or 30 mL/min/1.73m2 at screening or within 90 days of screening using the Schwartz formula in participants < 18 years of age (see Protocol Section 6.6.1)
7) Currently breastfeeding (nursing)
8) Known hypersensitivity to the study drug, the metabolites, or formulation excipient
9) Use or planned use of exclusionary medications, refer to Protocol Section 5.4 |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Composite endpoint of all-cause medically attended visits (MAVs) (medical visits attended in person by the participant and a health care professional) or death by Day 28
- The proportion of participants with treatment emergent adverse events
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At various timepoints as detailed in the Study Protocol |
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E.5.2 | Secondary end point(s) |
- All-cause mortality at Day 28
- Proportion of participants hospitalized by Day 28
- Composite endpoint of all-cause MAVs (medical visits attended in person by the participant and a health care professional) or death by Day 14
- Time-weighted average change in SARS-CoV-2 viral load from baseline to Day 7
- Time to alleviation (mild or absent) of baseline COVID-19 symptoms as reported in the COVID-19-adapted FLU-PRO Plus
- Proportion of participants progressing to requiring oxygen supplementation by Day 28 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At various timepoints as detailed in the Study Protocol |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Denmark |
France |
Germany |
Portugal |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 4 |