E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Coronavirus disease 2019 (COVID-19) in patients with chronic renal impairment |
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E.1.1.1 | Medical condition in easily understood language |
Coronavirus disease 2019 (COVID-19) in patients with loss of kidney function |
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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 | PT |
E.1.2 | Classification code | 10051905 |
E.1.2 | Term | Coronavirus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 whether RDV reduces the composite risk of death or IMV through Day 29 in participants with severely reduced kidney function who are hospitalized for COVID-19. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are as follows: - To evaluate whether RDV reduces the risk of death through Day 29 - To evaluate whether RDV reduces the risk of IMV through Day 29 - To evaluate the time to recovery (defined as satisfying category 1, 2, or 3 by the 8-point ordinal scale) - To evaluate the effect of RDV on clinical status assessed by an 8-point ordinal scale at Day 15 and Day 29 - To evaluate the effect of RDV on RRT-free days (among those without ESKD) through Day 29 - To evaluate the effect of RDV on recovery through Day 29 - To evaluate the safety and tolerability of RDV in participants with severely reduced kidney function who are hospitalized for COVID-19 |
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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) SARS-CoV-2 positive as determined by polymerase chain reaction (PCR) or other commercially available or public health assay (eg, nucleic acid amplification test and antigen tests) in any respiratory specimen 2) Hospitalized for COVID-19 3) Age ≥ 12 years and weighing at least 40 kg 4) O2 saturation ≤ 94% on room air or requiring O2 supplementation OR radiographic evidence of pulmonary infiltrates for COVID-19
5) Have either: a) Severely reduced kidney function (eGFR < 30 mL/min/1.73 m2), using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and revised Schwartz equations for adults and adolescents, respectively, including people with ESKD requiring chronic dialysis but not people requiring RRT for AKI {Levey 2009, Schwartz 2009} Adults: eGFR (mL/min/1.73 m²) 141 × min(Scr/κ, 1)α × max(Scr/κ, 1)-1.209 × 0.993Age × 1.018 [if female] × 1.159 [if African American] κ = 0.7 for females; 0.9 for males α = -0.329 for females; -0.411 for males Adolescents (age 12–17 years): eGFR (mL/min/1.73 m²) = (0.41 × Height in cm) / Scr SCr in mg/dL, age in years (See Appendix 7 of Protocol for web links to adult and adolescent eGFR calculators), OR b) Ongoing AKI: defined as a 50% increase in SCr within a 48-hour period that is sustained (ie, requires confirmatory SCr) for ≥ 6 hours despite supportive care
6) Willing and able to provide written informed consent, or with a legal representative who can provide informed consent, or enrolled under International Council for Harmonisation (of Technical Requirements for Pharmaceuticals for Human Use) (ICH) E6(R2) 4.8.15 emergency use provisions as deemed necessary by the investigator (age ≥18) prior to performing study procedures 7) The interval between COVID-19 symptoms onset and randomization is no more than 10 days 8) Male participants and female participants of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in Appendix 4 of the Protocol |
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E.4 | Principal exclusion criteria |
Participants who meet any of the following exclusion criteria at screening and randomization are not eligible to be enrolled in this study: 1) Received any investigational drug, RDV, or other antiviral treatment for COVID-19 2) ALT or AST > 5 × ULN 3) Invasive mechanical ventilation, noninvasive mechanical ventilation, ECMO, or RRT for AKI 4) Positive serum pregnancy test at screening for women of childbearing potential or currently breastfeeding 5) Known hypersensitivity to the investigational drug, metabolites, or formulation SBECD |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint: - The composite of all-cause mortality or invasive mechanical ventilation through Day 29
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At various timepoints throughout the study |
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E.5.2 | Secondary end point(s) |
The key (α-controlled) secondary endpoint of this study is as follows: - All-cause mortality through Day 29
Other secondary endpoints: - Invasive mechanical ventilation through Day 29 - Time to recovery (defined as satisfying category 1, 2, or 3 by the 8-point ordinal scale) - Clinical status assessed by an 8-point ordinal scale on Day 15 and Day 29 - RRT-free days (among those without ESKD at randomization) through Day 29 - Recovery through Day 29 - Serious adverse events (SAEs) and AEs leading to investigational drug discontinuation |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At various timepoints throughout the study |
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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 | Yes |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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 |
Colombia |
Mexico |
South Africa |
Argentina |
Brazil |
India |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |