E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Coronavirus disease 2019 (COVID-19) |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 |
|
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 |
Cohort A (A): SARS-CoV-2 RT-qPCR Negative at Baseline: 1. To evaluate the efficacy of REGN10933+REGN10987 (REGN-COV2) compared to placebo in preventing symptomatic SARS-CoV-2 infection (strict-term) confirmed by RT-qPCR
2. To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in preventing asymptomatic or symptomatic SARS-CoV-2 infection confirmed by RT-qPCR
3. To evaluate the safety and tolerability of REGN10933+REGN10987 following subcutaneous (SC) administration compared to placebo
Cohort B (B): SARS-CoV-2 RT-qPCR Positive at Baseline: no primary objectives |
|
E.2.2 | Secondary objectives of the trial |
-Efficacy of REGN10933+REGN10987 vs placebo in preventing (broad-term/strict-term) symptomatic SARS-CoV2 (Cohort A,B) -Efficacy of REGN10933+REGN10987 vs placebo in preventing asymptomatic SARS-CoV2 (Cohort A) -Impact of REGN10933+REGN10987 vs placebo on duration of signs/symptoms in symptomatic SARS-CoV2 (Cohort A,B) -Impact of REGN10933+REGN10987 vs placebo on SARS-CoV2 test results (Cohort A,B) -Impact of REGN10933+REGN10987 vs placebo on SARS-CoV2 on health care utilization, absenteeism (Cohort A,B) -Drug concentration-time profiles of REGN10933 and REGN10987 (Cohort A,B) -Immunogenicity of REGN10933 and REGN10987 (Cohort A,B) -Safety/tolerability of REGN10933+REGN10987 in sero+ subjects (Cohort A) -Safety/tolerability of REGN10933+REGN10987 in sero-/sero+ subjects (Cohort B) -Incidence/severity of symptomatic SARS-CoV2 over time in REGN10933+REGN10987-treated sero-/sero+ subjects vs placebo-treated subjects (Cohort A, B) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Asymptomatic household contact with sustained exposure (at least 48 hours) to an individual with a diagnosis of SARS-CoV-2 infection (index case). To be included in the study, subjects must be randomized within 96 hours of collection of the index cases’ positive SARS-COV-2 diagnostic test sample 2. Subject anticipates living in the same household with the index case until study day 29 3. Is judged by the investigator to be in good health based on medical history and physical examination at screening/baseline, including subjects who are healthy or have a chronic, stable medical condition 4. Willing and able to comply with study visits and study-related procedures/assessments. 5. Provide informed consent signed by study subject or legally acceptable representative. |
|
E.4 | Principal exclusion criteria |
1. History of prior positive SARS-CoV-2 RT-PCR test or positive SARS-CoV-2 serology test at any time before the screening 2. Subject has lived with individuals who have had previous SARS-CoV-2 infection 3. Active respiratory or non-respiratory symptoms consistent with COVID-19 4. History of respiratory illness with sign/symptoms of SARS-CoV-2 infection, in the opinion of the investigator within the prior month to screening 5. Nursing home resident 6. Any physical examination findings, and/or history of any illness, concomitant medications or recent live vaccines that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the subject by their participation in the study
NOTE: Other Protocol defined exclusion criteria apply |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Cohort A (SARS-CoV-2 RT-qPCR Negative at Baseline): 1.Proportion of subjects who have a positive SARS-CoV-2 RT-qPCR (based on central lab test) and signs and symptoms (strict-term) of SARS-CoV-2 infection during the EAP 2.Proportion of subjects who have a RT-qPCR confirmed SARS-CoV-2 infection (either asymptomatic or symptomatic) during the EAP 3.Proportion of subjects with TEAEs and severity of TEAEs.
Cohort B: no primary endpoints |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to 1 month 2. Up to 1 month 3. Up to 8 months |
|
E.5.2 | Secondary end point(s) |
Cohort A (A): SARS-CoV-2 RT-qPCR Negative at Baseline; Cohort B (B): SARS-CoV-2 RT-qPCR Positive at Baseline 1. Proportion of participants who have a symptomatic RT-qPCR confirmed SARS-CoV-2 infection (broad term) during the EAP (A) 2. Proportion of participants who have a positive SARS-CoV-2 RT-qPCR and absence of signs and symptoms (strict term) during the EAP (A) 3. Proportion of participants who have a positive SARS-CoV-2 RT-qPCR and absence of signs and symptoms (broad term) during the EAP (A) 4. Number of days of symptomatic SARS-CoV-2 infection (strict-term) from the first day of the first sign or symptom until the last day of the last sign or symptom associated with the first positive SARS-CoV-2 RT-PCR that occurs during the EAP (A) 5. Number of days of symptomatic SARS-CoV-2 infection (broad-term) from the first day of the first sign or symptom until the last day of the last sign or symptom associated with the first positive SARS-CoV-2 RT-PCR that occurs during the EAP (A) 6. Time-weighted average of viral shedding (log10 copies/mL) from the first positive SARS CoV-2 RT-qPCR Nasopharyngeal (NP) swab sample (with an onset during the EAP) until the visit within the window including 22 days after the positive test during the EAP (A) 7. Maximum SARS-CoV-2 RT-qPCR log10 viral copies/mL in Nasopharyngeal (NP) swab samples among individuals with ≥1 RT-qPCR positive that has an onset during the EAP (A) 8. Maximum SARS-CoV-2 RT-qPCR log10 viral copies/mL in NP swab samples (B) 9. Area under the curve (AUC) in viral shedding (log10 copies/mL) from the first positive SARS-CoV-2 RT-qPCR NP swab sample until the first confirmed negative test, that has an onset during the EAP (A,B) 10. Number of medically attended visits in emergency rooms or urgent care centers related to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP (A,B) 11. Proportion of participants requiring medically attended visits in emergency rooms or urgent care centers related to a RT-qPCR confirmed SARS CoV-2 infection that has an onset during the EAP (A,B) 12. Proportion of participants hospitalized related to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP (A,B) 13. Number of days of hospital and intensive care unit (ICU) stay in subjects hospitalized for a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP (A,B) 14. Number of days missed for daily responsibilities due to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP (A,B) 15. Concentrations of REGN10933 in serum over time and selected PK parameters (A,B) 16. Concentrations of REGN10987 in serum over time and selected PK parameters (A,B) 17. Immunogenicity as measured by anti-drug antibodies (ADA) to REGN10933 over time (A,B) 18. Immunogenicity as measured by anti-drug antibodies (ADA) to REGN10987 over time (A,B) 19. Incidence and severity of TEAEs in baseline seropositive participants (based on central lab test) (A) 20. Incidence and severity of symptomatic SARS-CoV-2 infection (A,B) 21. Proportion of participants who subsequently develop signs and symptoms (strict-term) of symptomatic SARS-CoV-2 infection during EAP (B) 22. Proportion of participants who subsequently develop signs and symptoms (broad-term) of symptomatic SARS-CoV-2 infection during EAP (B) 23. Number of days of symptomatic SARS CoV-2 infection (strict-term) (B) 24. Number of days of symptomatic SARS CoV-2 infection (broad-term) (B) 25. Time-weighted average change from baseline in viral shedding in NP swab samples until the visit within the window including day 23 (B) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 Up to 1 month 2 Up to 1 month 3 Up to 1 month 4 Up to 8 months 5 Up to 8 months 6 Up to 1 month 7 Up to 1 month 8 Up to 8 months 9 Up to 8 months 10 Up to 8 months 11 Up to 8 months 12 Up to 8 months 13 Up to 8 months 14 Up to 8 months 15 Up to 8 months 16 Up to 8 months 17 Up to 8 months 18 Up to 8 months 19 Up to 8 months 20 Up to 8 months 21 Within 14 and 28 days of a positive RT-qPCR 22 Within 14 and 28 days of a positive RT-qPCR 23 Up to 8 months 24 Up to 8 months 25 Until day 23 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
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
| 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 |
Moldova, Republic of |
|
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
|
|
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 | 2 |
E.8.9.1 | In the Member State concerned days | |
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 | 2 |