COVID-19 Study Assessing the Virologic Efficacy of REGN10933+REGN10987 Across Different Dose Regimens in Adult Outpatients With SARS-CoV-2 Infection

Study Overview
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Brief Summary
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The primary objective of the study is to assess the virologic efficacy of REGN10933+REGN10987 across different intravenous and subcutaneous doses compared to placebo. The secondary objectives of the study are: To evaluate additional indicators of virologic efficacy of REGN10933+REGN10987 compared to placebo To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo To assess the concentrations of REGN10933 and REGN10987 in serum over time To assess the immunogenicity of REGN10933 and REGN10987

Official Title
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A Phase 2 Study to Assess the Virologic Efficacy of REGN10933+REGN10987 Across Different Dose Regimens in Outpatients With SARS-CoV-2 Infection

Conditions
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COVID-19

Intervention / Treatment
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* Drug: REGN10933+REGN10987 combination therapy
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Has SARS-CoV-2-positive diagnostic test from a sample collected ≤72 hours prior to randomization, as defined by the protocol Low-risk symptomatic patient: Has symptoms consistent with COVID-19 (as determined by the investigator) with onset ≤7 days before randomization, and meets all of the following 8 criteria: Age ≤50 No obesity, with obesity defined as BMI ≥30 kg/m2 Does not have cardiovascular disease or hypertension Does not have chronic lung disease or asthma Does not have type 1 or type 2 diabetes mellitus Does not have chronic kidney disease, with or without dialysis Does not have chronic liver disease Is not pregnant or Asymptomatic patient: Has had no symptoms consistent with COVID-19 (as determined by the investigator) occurring at any time <2 months prior to randomization Maintains O2 saturation ≥93% on room air Key Exclusion Criteria: Was admitted to a hospital for COVID-19 prior to randomization, or is hospitalized (inpatient) for any reason at randomization Has a known positive SARS-CoV-2 serologic test Has a positive SARS-CoV-2 antigen or molecular diagnostic test from a sample collected >72 hours prior to randomization Is immunosuppressed, based on investigator's assessment Has participated, or is participating, in a clinical research study evaluating COVID-19 convalescent plasma, mAbs against SARS-CoV-2, or intravenous immunoglobulin (IVIG) within 3 months or within 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, (eg, bamlanivimab), IVIG (any indication), systemic corticosteroids (any indication), or COVID-19 treatments (authorized, approved, or investigational) Prior use (prior to randomization), current use (at randomization), or planned use (within time period given per CDC guidance but no sooner than 22 days of study drug administration) of any authorized or approved vaccine for COVID-19 Has known active infection with influenza or other non-SARS-CoV-2 respiratory pathogen, confirmed by a diagnostic test Has participated, is participating, or plans to participate in a clinical research study evaluating any authorized, approved, or investigational vaccine for COVID-19 NOTE: Other protocol defined inclusion/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IV Dose 1<br>Combination therapy intravenous (IV) single dose | Drug: REGN10933+REGN10987 combination therapy<br>* Administered IV or SC single dose<br>* Other names: imdevimab;|
| Experimental: IV Dose 2<br>Combination therapy IV single dose | Drug: REGN10933+REGN10987 combination therapy<br>* Administered IV or SC single dose<br>* Other names: imdevimab;|
| Experimental: IV Dose 3<br>Combination therapy IV single dose | Drug: REGN10933+REGN10987 combination therapy<br>* Administered IV or SC single dose<br>* Other names: imdevimab;|
| Experimental: IV Dose 4<br>Combination therapy IV single dose | Drug: REGN10933+REGN10987 combination therapy<br>* Administered IV or SC single dose<br>* Other names: imdevimab;|
| Experimental: Placebo IV Dose<br>Matching placebo IV single dose | Drug: Placebo<br>* Administered IV or SC single dose to match<br>|
| Experimental: SC Dose 1<br>Combination therapy subcutaneous (SC) single dose | Drug: REGN10933+REGN10987 combination therapy<br>* Administered IV or SC single dose<br>* Other names: imdevimab;|
| Experimental: SC Dose 2<br>Combination therapy SC single dose | Drug: REGN10933+REGN10987 combination therapy<br>* Administered IV or SC single dose<br>* Other names: imdevimab;|
| Experimental: Placebo SC Dose<br>Matching placebo SC single dose | Drug: Placebo<br>* Administered IV or SC single dose to match<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-Weighted Average Daily Change From Day 1 in Viral Load in NP Swab Samples | Time-weighted average daily change from Day 1 in viral load (log10 copies/mL), as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples. | Day 1 to Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-Weighted Average Daily Change From Day 1 in Viral Load | Time-weighted average daily change from Day 1 in viral load (log10 copies/mL) as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples. | Day 1 to Day 5 | 
| Time-Weighted Average Daily Change From Day 1 in Viral Load in Participants With High Viral Load at Baseline | Time-weighted average daily change from Day 1 in viral load (log10 copies/mL) as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples. in any participant with a viral load greater than 10,000 copies/mL at baseline. | Day 1 to Day 7 | 
| Time-Weighted Average Daily Change From Day 1 in Viral Load in Participants With High Viral Load at Baseline | Time-weighted average daily change from Day 1 in viral load (log10 copies/mL) as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples. in any participant with a viral load greater than 10,000 copies/mL at baseline. | Day 1 to Day 5 | 
| Number of Participants With High Viral Load | Number of participants with viral load greater than 10,000 copies/mL, as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples. | Day 1, Day 3, Day 5, Day 7, Day 15, Day 22 | 
| Number of Participants With Viral Loads Below the Limit of Detection | Number of participants with viral load less than 299 copies/mL, as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples. | Day 1, Day 3, Day 5, Day 7, Day 15, Day 22 | 
| Number of Participants With Viral Loads Below the Lower Limit of Quantification | Number of participants with viral load less than 714 copies/mL, as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples. | Day 1, Day 3, Day 5, Day 7, Day 15, Day 22 | 
| Change From Day 1 in Viral Load as Measured by RT-qPCR in NP Swab Samples | Change from Day 1 in Viral Load (log10 copies/mL) as Measured by Quantitative reverse transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) Swab Samples | Day 3, Day 5, Day 7, Day 15, Day 22 | 
| Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs) |  | Through day 29 | 
| Number of Participants With Infusion-Related Reactions Grade 2 or Above |  | Through day 4 | 
| Number of Participants With Injection-Site Reactions Grade 3 or Above |  | Through day 4 | 
| Number of Participants With Hypersensitivity Reactions Grade 2 or Above |  | Through day 29 | 
| Concentration of REGN10933 in Serum |  | Pre-Dose, 15 minutes Post-Dose, 3 days Post-Dose, 5 days Post-Dose, 7 days Post-Dose, 120 days Post-Dose | 
| Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10933 |  | Through day 120 | 
| Immunogenicity as Measured by Neutralizing Anti-drug Antibody (NAb) to REGN10933 |  | Through day 120 | 
| Concentration of REGN10987 in Serum |  | Pre-Dose, 15 minutes Post-Dose, 3 days Post-Dose, 5 days Post-Dose, 7 days Post-Dose, 120 days Post-Dose | 
| Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10987 |  | Through day 120 | 
| Immunogenicity as Measured by Neutralizing Anti-drug Antibody (NAb) to REGN10987 |  | Through day 120 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) coronavirus, Non-hospitalized