E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Coronavirus disease 2019 (COVID-19) |
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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 | 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 |
Phase 1: -To evaluate the safety and tolerability of REGN10933+REGN10987 vs placebo -To evaluate the virologic efficacy of REGN10933+REGN10987 vs placebo in reducing viral shedding of SARS-CoV-2
Phase 2: -To evaluate the virologic efficacy of REGN10933+REGN10987 vs placebo in reducing viral shedding of SARS-CoV-2
Phase 3: -To evaluate the clinical efficacy of REGN10933+REGN10987 vs placebo |
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E.2.2 | Secondary objectives of the trial |
Phase 1 -Evaluate additional indicators of virologic efficacy of REGN10933+REGN10987 (REGN-COV2) vs placebo -Estimate clinical efficacy of REGN-COV2 vs placebo -Compare RT-qPCR results acquired with different sample types -Characterize PK profiles of REGN10933 and REGN10987 in serum -Assess immunogenicity of REGN10933 and REGN10987 Phase 2 -Evaluate additional indicators of virologic efficacy of REGN-COV2 vs placebo -Evaluate clinical efficacy of REGN-COV2 vs placebo -Evaluate safety and tolerability of REGN-COV2 vs placebo -Compare RT-qPCR results acquired with different sample types -Characterize concentrations of REGN10933 and REGN10987 in serum -Assess immunogenicity of REGN10933 and REGN10987 Phase 3 -Evaluate virologic efficacy of REGN-COV2 vs placebo in reducing viral shedding of SARS CoV 2 -Evaluate safety and tolerability of REGN-COV2 vs placebo -Characterize concentrations of REGN10933 and REGN10987 in serum -Assess immunogenicity of REGN10933 and REGN10987 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Key Inclusion Criteria: -Has SARS-CoV-2-positive antigen or molecular diagnostic test (by validated SARS-CoV-2 antigen, RT-PCR, or other molecular diagnostic assay, using an appropriate sample such as NP, nasal, oropharyngeal [OP], or saliva) ≤72 hours prior to randomization. A historical record of positive result from test conducted ≤72 hours prior to randomization is acceptable. -Meets one of the following 2 criteria: a. Symptomatic Cohort (All Phases): Has symptoms consistent with COVID-19, as determined by the investigator, with onset ≤7 days before randomization or b. Asymptomatic Cohort (Phase 2): Meets all of the following: -Has had no symptoms consistent with COVID-19 (as determined by the investigator) occurring at any time <2 months prior to randomization -Has had no positive SARS-CoV-2 test results from a sample collected >7 days prior to randomization -Has had no known contact (of any duration) with an individual who has confirmed COVID-19 or confirmed positive SARS-COV-2 test result >14 days prior to randomization.
NOTE: Other Protocol defined Inclusion criteria apply |
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E.4 | Principal exclusion criteria |
Key Exclusion Criteria: -Has been admitted to a hospital prior to randomization, or is hospitalized (inpatient) at randomization, due to COVID-19 -Has participated, or is participating, in a clinical research study evaluating COVID-19 convalescent plasma, monoclonal antibodies (mAbs) against SARS-CoV-2, or intravenous immunoglobulin (IVIG) within 3 months or less than 5 half-lives of the investigational product (whichever is longer) prior to the screening visit -Prior, current, or planned future use of any of the following treatments: COVID-19 convalescent plasma, mAbs against SARS-CoV-2, intravenous immunoglobulin (IVIG) (any indication), systemic corticosteroids (any indication), or COVID-19 EUA-approved treatments, where prior use is defined as the past 30 days or less than 5 half-lives of the investigational product (which is longer) from screening
NOTE: Other Protocol defined Exclusion criteria apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase 1 a)Proportion of patients with treatment-emergent SAEs b)Proportion of patients with infusion-related reactions (grade ≥2) c)Proportion of patients with hypersensitivity reactions (grade ≥2) d)Time-weighted average change from baseline in viral shedding, as measured by RT-qPCR in NP swab samples. Phase 2 Time-weighted average change from baseline in viral shedding, as measured by RT-qPCR in NP swab samples. Phase 3 Proportion of patients with ≥1 COVID 19 related medically-attended visit |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase 1 a)Through day 29 b)Through day 4 c)Through day 29 d)Through day 22, Phase 2: Through day 22 Phase 3: Through day 29 |
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E.5.2 | Secondary end point(s) |
1. Time-weighted average change from baseline in viral shedding measured by RT-qPCR in saliva samples (Phase 1 Only) 2. Time-weighted average change from baseline in viral shedding measured by RT-qPCR in nasal swab samples (Phase 1 Only) 3. Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR in any tested samples (Phase 1 Only) 4. Time to negative RT-qPCR in NP swabs with no subsequent positive RT-qPCR (Phase 2, Phase 3) 5. Change from baseline in viral shedding as measured by RT-qPCR in NP swabs 6. Change from baseline in viral shedding as measured by RT-qPCR in saliva samples (Phase 1 Only) 7. Change from baseline in viral shedding as measured by RT-qPCR in nasal swabs (Phase 1 Only) 8. Correlation of RT-qPCR results over time between different sample types (NP, nasal, and saliva) (Phase 1 Only) 9. Concordance of RT-qPCR results over time between different sample types (NP, nasal, and saliva) (Phase 1 Only) 10. Time-weighted average change from baseline in viral shedding 11. Proportion of patients with at least two COVID-19 related medically attended visits 12. Total number of COVID-19 related medically-attended visits 13. Proportion of patients admitted to a hospital due to COVID-19 14. Proportion of patients admitted to an intensive care unit (ICU) due to COVID-19 (Phase 2, Phase 3) 15. Proportion of patients at least 1 outpatient or telemedicine visit due to COVID-19 16. Proportion of patients requiring mechanical ventilation due to COVID-19 (Phase 2, Phase 3) 17. Number of days of hospitalization due to COVID-19 (Phase 2, Phase 3) 18. Number of deaths due to any cause (All-Cause Mortality) (Phase 2, Phase 3) 19. Serum concentration of REGN10933 over time 20. Serum concentration of REGN10987 over time 21. Assessment of PK parameter: maximum serum concentration observed (Cmax) of REGN10933 and REGN10987 (Phase 1 only) 22. Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) of REGN10933 and REGN10987 (Phase 1 only) 23.Assessment of PK parameter: Time to Cmax (tmax) for REGN10933 and REGN10987 (Phase 1 only) 24. Assessment of PK parameter: Area Under the Curve (AUC) computed from time zero to the time of the last positive concentration (AUClast) for REGN10933 and REGN10987 (Phase 1 only) 25. Incidence of anti-drug antibodies (ADA) to REGN10933 and REGN10987 26. Time to first onset of symptoms consistent with COVID-19 (asymptomatic cohort only) 27. Duration of symptoms consistent with COVID-19 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Baseline up to Day 22 2. Baseline up to Day 22 3. Through Day 29 4. Through Day 29 5. Baseline up to Day 29 6. Baseline up to Day 29 7. Baseline up to Day 29 8. Up to Day 29 9. Up to Day 29 10. Baseline up to Day 29 11. Through Day 29 12. Through Day 29 13. Through Day 29 14. Through Day 29 15. Through Day 29 16. Through Day 29 17. Through Day 29 18. Through Day 29 19. Through Day 29 20. Through Day 29 21. Through Day 29 22. Through Day 29 23. Through Day 29 24. Through Day 29 25. Through Day 29 26. Through Day 29 27. Through Day 29 |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | Yes |
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 | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 |
Brazil |
Chile |
Mexico |
United States |
Romania |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |