COVID-19 Study to Evaluate Safety, Tolerability, and Efficacy of REGN14256+Imdevimab for the Treatment of COVID-19 Adult and Adolescent Patients Without Risk Factors for Progression to Severe Disease

Study Overview
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Brief Summary
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Primary Objectives Phase 1 (Safety and Tolerability) • Evaluate the safety and tolerability of REGN14256+imdevimab and REGN14256 monotherapy, as measured by treatment-emergent adverse events (TEAEs), injection-site reactions (ISRs), and hypersensitivity reactions Phase 1/2 (Virologic Efficacy) • Evaluate the virologic efficacy of REGN14256+imdevimab and REGN14256 monotherapy compared to placebo, as measured by time-weighted average (TWA) change from baseline in viral load through day 7 Phase 1/2/3 (Clinical Efficacy) • Evaluate the clinical efficacy of REGN14256+imdevimab compared to placebo, as measured by COVID-19 symptoms resolution Secondary Objectives Phase 1 (Safety and Tolerability) • Evaluate the safety and tolerability of REGN14256+imdevimab and REGN14256 monotherapy, as measured by treatment-emergent serious adverse events (SAEs) Phase 2 and Phase 3 (Safety and Tolerability) • Evaluate the safety and tolerability of REGN14256+imdevimab and REGN14256 monotherapy, as measured by TEAEs, ISRs, hypersensitivity reactions, and SAEs Phase 1, Phase 2, and Phase 3 (Virologic Efficacy, Drug Concentration, and Immunogenicity) Evaluate additional indicators of virologic efficacy of REGN14256+imdevimab and REGN14256 monotherapy Characterize the concentration-time profile of REGN14256 administered in combination with imdevimab or alone as a monotherapy Assess the immunogenicity of REGN14256 administered in combination with imdevimab or alone as a monotherapy

Official Title
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A Phase 1/2/3 Adaptive Study to Evaluate the Safety, Tolerability, and Efficacy of REGN14256+Imdevimab for the Treatment of COVID-19 Patients Without Risk Factors for Progression to Severe Disease

Conditions
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SARS-CoV-2

Intervention / Treatment
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* Drug: REGN14256
* Drug: imdevimab
* Drug: casirivimab + imdevimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Phase 1 will enroll adult patients (≥18 years of age), Phase 2 will enroll adult patients, Phase 3 will enroll adult patients and an additional adolescent cohort of patients (≥12 and <18 years of age) Key Inclusion Criteria: For the adolescent cohort in Phase 3 only: Weighs ≥40 kg at randomization Has SARS-CoV-2-positive antigen or molecular diagnostic test (by validated SARSCoV-2 antigen, RT-PCR, or other molecular diagnostic assay, using an appropriate sample such as nasopharyngeal [NP], nasal, oropharyngeal [OP], or saliva) ≤72 hours prior to randomization. A historical record of a positive result is acceptable as long as the sample was collected ≤72 hours prior to randomization Has symptoms consistent with COVID-19 (as determined by the investigator) with onset ≤7 days before randomization, and doesn't have a medical condition or other factors associated with high risk for progression to severe COVID-19 as outlined in the exclusion criteria Maintains O2 saturation ≥93% on room air Key Exclusion Criteria: Has a medical condition or other factors associated with high risk for progression to severe COVID-19: Cancer Cardiovascular disease (such as heart failure, coronary artery disease, cardiomyopathies, congenital heart disease or hypertension) Chronic lung disease including chronic obstructive pulmonary disease, asthma (moderate to severe), interstitial lung disease, cystic fibrosis, and pulmonary hypertension Chronic kidney disease at any stage Chronic liver disease (such as alcohol-related, nonalcoholic fatty liver disease, cirrhosis) Dementia or other chronic neurological condition Diabetes mellitus (type 1 or type 2) Immunodeficiency disease or taking immunosuppressive treatment Medical-related technological dependence [for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19)] Neurodevelopmental disorder (for example, cerebral palsy) or other condition that confers medical complexity (for example, genetic or metabolic syndromes and severe congenital anomalies) Overweight (defined as BMI >25 kg/m2) or obesity (defined as BMI ≥30 kg/m2) Poorly controlled HIV infection or AIDS Pregnancy Sickle cell disease or thalassemia Stroke or cerebrovascular disease Prior, current (at randomization) or planned use (within time period given per CDC guidance [90 days]) of any authorized or approved vaccine for COVID-19 Was admitted to a hospital for COVID-19 prior to randomization, or is hospitalized (inpatient) for any reason at randomization Has a known prior SARS-CoV-2 infection or 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 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 any of the following treatments: COVID-19 convalescent plasma, mAbs against SARS-CoV-2, IVIG (any indication), systemic corticosteroids (any indication), or COVID-19 treatments (authorized, approved, or investigational) Has known active infection with influenza or other non-SARS-CoV-2 respiratory pathogen, confirmed by a diagnostic test Has been discharged, or is planned to be discharged, to a quarantine center Has participated, is participating, or plans to participate in a clinical research study evaluating any authorized, approved, or investigational vaccine for COVID-19 For Phase 1only: Women of childbearing potential (WOCBP) who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment and for at least 6 months after study drug administration as described in the protocol Note: Other protocol-defined inclusion/ exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 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
Interventional Model Description: Phase1/Phase2/Phase3
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: REGN14256 + imdevimab<br>Phase 1, Phase 2: Randomized 1:1:1:1:1 Phase 3: (≥18 Years): Randomized 1:1:1 Phase 3: (Open label) (≥12 and <18 Years) | Drug: REGN14256<br>* Sub-cutaneous (SC) single dose<br>Drug: imdevimab<br>* SC single dose<br>* Other names: REGN10987;|
| Experimental: REGN14256<br>Phase 1, Phase 2: Randomized 1:1:1:1:1 | Drug: REGN14256<br>* Sub-cutaneous (SC) single dose<br>|
| Experimental: Imdevimab<br>Phase 1, Phase 2: Randomized 1:1:1:1:1 | Drug: imdevimab<br>* SC single dose<br>* Other names: REGN10987;|
| Experimental: casirivimab + imdevimab<br>Phase 1, Phase 2: Randomized 1:1:1:1:1 Phase 3: (≥18 Years): Randomized 1:1:1 | Drug: imdevimab<br>* SC single dose<br>* Other names: REGN10987;Drug: casirivimab + imdevimab<br>* SC single dose<br>* Other names: Ronapreve™;|
| Experimental: Placebo<br>Phase 1, Phase 2: Randomized 1:1:1:1:1 Phase 3: (≥18 Years): Randomized 1:1:1 | Drug: Placebo<br>* SC single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment emergent adverse events (TEAEs) | Phase 1 | Through Day 29 | 
| Severity of TEAEs | Phase 1 | Through Day 29 | 
| Proportion of patients with injection-site reactions (ISRs) | Phase 1 | Through Day 169 | 
| Severity of ISRs | Phase 1 | Through Day 169 | 
| Proportion of patients with hypersensitivity reactions | Phase 1 | Through Day 169 | 
| Severity of hypersensitivity reactions over time | Phase 1 | Through Day 169 | 
| Time-weighted average (TWA) daily change from baseline in viral load (log10 copies/mL) | Phase 1/2 Measured by SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples | Day 1 to day 7 | 
| Time to COVID-19 symptoms resolution | Phase 1/2/3 | Through Day 169 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with treatment-emergent serious adverse events (SAEs) | Phase 1 | Through Day 169 | 
| TEAEs | Phase 2 and Phase 3 | Through Day 29 | 
| Severity of TEAEs | Phase 2 and Phase 3 | Through Day 29 | 
| Proportion of patients with ISRs | Phase 2 and Phase 3 | Through Day 169 | 
| Severity of ISRs | Phase 2 and Phase 3 | Through Day 169 | 
| Proportion of patients with hypersensitivity reactions | Phase 2 and Phase 3 | Through Day 169 | 
| Severity of hypersensitivity reactions over time | Phase 2 and Phase 3 | Through Day 169 | 
| Proportion of patients with treatment-emergent SAEs | Phase 2 and Phase 3 | Through Day 169 | 
| Time-weighted average change from baseline in viral load | Phase 1, Phase 2, and Phase 3 Measured by RT-qPCR in NP samples | Through Day 169 | 
| Change from baseline in viral load | Phase 1, Phase 2, and Phase 3 As measured by RT-qPCR in NP samples | Through Day 7 | 
| Proportion of patients with viral loads below the limit of detection | Phase 1, Phase 2, and Phase 3 | Through Day 169 | 
| Concentrations of REGN14256 in serum over time | Phase 1, Phase 2, and Phase 3 | Through Day 169 | 
| Concentrations of imdevimab in serum over time | Phase 1, Phase 2, and Phase 3 | Through Day 169 | 
| Incidence and titer of anti-drug antibodies (ADA) to REGN14256 over time | Phase 1, Phase 2, and Phase 3 | Through Day 169 | 
| Incidence and titer of ADA to imdevimab over time | Phase 1, Phase 2, and Phase 3 | Through Day 169 | 

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