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

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

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

Study Overview

• Status: Terminated
• Conditions: SARS-CoV-2
• Intervention / Treatment: Drug: REGN14256; Drug: imdevimab; Drug: casirivimab + imdevimab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • La Mesa, California, United States, 91941
      • Regeneron Research Site
    • Long Beach, California, United States, 90806
      • ARK Clinical Research
    • Mission Viejo, California, United States, 92691
      • PNS Clinical Research, LLC
  • Florida
    • Ft. Pierce, Florida, United States, 34982
      • Regeneron Research Site
    • Hialeah, Florida, United States, 33012
      • AGA Clinical Trials
    • Loxahatchee Groves, Florida, United States, 33470
      • Regeneron Research Site
    • Miami, Florida, United States, 33125
      • Project 4 Research, Inc.
    • Miami, Florida, United States, 33126
      • Universal Medical and Research Center, LLC
    • Miami, Florida, United States, 33174
      • Global Medical Trials
    • Miami, Florida, United States, 33184
      • Bio-Medical Research LLC
    • Miami Lakes, Florida, United States, 33014
      • Charisma Research and Medical Center
    • West Palm Beach, Florida, United States, 33407
      • Triple O Research Institute, P.A.
    • Winter Park, Florida, United States, 32789
      • Regeneron Research Site
  • Georgia
    • Columbus, Georgia, United States, 31904
      • IACT Health
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Chicago Clinical Research Institute
  • Iowa
    • Ames, Iowa, United States, 50010
      • Regeneron Research Site
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Regeneron Research Site
  • Mississippi
    • Olive Branch, Mississippi, United States, 38654
      • Olive Branch Family Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89103
      • Forte Family Practice
  • New York
    • The Bronx, New York, United States, 10451
      • New York Health and Hospitals / Lincoln
    • The Bronx, New York, United States, 10461
      • NYC H+H / Jacobi Medical Center
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Regeneron Research Site
  • Ohio
    • Dayton, Ohio, United States, 45409
      • Regeneron Research Site
  • South Carolina
    • Clinton, South Carolina, United States, 29325
      • Carolina Medical Research
  • Texas
    • Amarillo, Texas, United States, 79109
      • PharmaTex Research, LLC
    • Houston, Texas, United States, 77027
      • Advanced Diagnostics Clinic, River Oaks Hospital and Clinics
    • Houston, Texas, United States, 77030
      • Regeneron Research Site
    • Houston, Texas, United States, 77093
      • Regeneron Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

1. For the adolescent cohort in Phase 3 only: Weighs ≥40 kg at randomization
2. 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
3. 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
4. Maintains O2 saturation ≥93% on room air

Key Exclusion Criteria:

1. Has a medical condition or other factors associated with high risk for progression to severe COVID-19:

   1. Cancer
   2. Cardiovascular disease (such as heart failure, coronary artery disease, cardiomyopathies, congenital heart disease or hypertension)
   3. Chronic lung disease including chronic obstructive pulmonary disease, asthma (moderate to severe), interstitial lung disease, cystic fibrosis, and pulmonary hypertension
   4. Chronic kidney disease at any stage
   5. Chronic liver disease (such as alcohol-related, nonalcoholic fatty liver disease, cirrhosis)
   6. Dementia or other chronic neurological condition
   7. Diabetes mellitus (type 1 or type 2)
   8. Immunodeficiency disease or taking immunosuppressive treatment
   9. Medical-related technological dependence [for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19)]
   10. Neurodevelopmental disorder (for example, cerebral palsy) or other condition that confers medical complexity (for example, genetic or metabolic syndromes and severe congenital anomalies)
   11. Overweight (defined as BMI >25 kg/m2) or obesity (defined as BMI ≥30 kg/m2)
   12. Poorly controlled HIV infection or AIDS
   13. Pregnancy
   14. Sickle cell disease or thalassemia
   15. Stroke or cerebrovascular disease
2. 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
3. Was admitted to a hospital for COVID-19 prior to randomization, or is hospitalized (inpatient) for any reason at randomization
4. Has a known prior SARS-CoV-2 infection or positive SARS-CoV-2 serologic test
5. Has a positive SARS-CoV-2 antigen or molecular diagnostic test from a sample collected >72 hours prior to randomization
6. 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
7. 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)
8. Has known active infection with influenza or other non-SARS-CoV-2 respiratory pathogen, confirmed by a diagnostic test
9. Has been discharged, or is planned to be discharged, to a quarantine center
10. Has participated, is participating, or plans to participate in a clinical research study evaluating any authorized, approved, or investigational vaccine for COVID-19
11. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: REGN14256 + imdevimab; 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; Sub-cutaneous (SC) single dose; Drug: imdevimab; SC single dose; Other Names: REGN10987
Experimental: REGN14256; Phase 1, Phase 2: Randomized 1:1:1:1:1	Drug: REGN14256; Sub-cutaneous (SC) single dose
Experimental: Imdevimab; Phase 1, Phase 2: Randomized 1:1:1:1:1	Drug: imdevimab; SC single dose; Other Names: REGN10987
Experimental: casirivimab + imdevimab; Phase 1, Phase 2: Randomized 1:1:1:1:1 Phase 3: (≥18 Years): Randomized 1:1:1	Drug: imdevimab; SC single dose; Other Names: REGN10987; Drug: casirivimab + imdevimab; SC single dose; Other Names: REGN10933 + REGN10987; REGN-COV2; REGEN-COV™; Ronapreve™
Experimental: Placebo; Phase 1, Phase 2: Randomized 1:1:1:1:1 Phase 3: (≥18 Years): Randomized 1:1:1	Drug: Placebo; SC single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Emergent Adverse Events (TEAEs)	Phase 1	Through Day 29
Severity of TEAEs	Severity was based on Grading. Grade 1 was less severe. Grade 5 was more severe.; - Mild; Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; - Moderate; Minimal, local, or noninvasive intervention indicated; limiting age appropriate instrumental activities of daily living (ADL); - Severe; Severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; ADL2 limiting self-care; - Life-threatening; Life threatening consequences; urgent intervention indicated; - Death; Death related to adverse events	Through Day 29
Percentage of Participants With Injection-site Reactions (ISRs)	Phase 1 only	Through Day 169
Severity of ISRs (Injection Site Reactions)	Severity was based on Grading. Grade 1 was less severe. Grade 5 was more severe. Grade 1 - Tenderness with or without associated symptoms (eg, warmth, erythema, itching) Grade 2 - Pain; lipodystrophy; edema; phlebitis Grade 3 - Ulceration or necrosis; severe tissue damage; operative intervention indicated Grade 4 - Life-threatening consequences; urgent intervention indicated Grade 5 - Death	Through Day 29
Percentage of Participants With Hypersensitivity Reactions	Phase 1	Through Day 169
Severity of Hypersensitivity Reactions Over Time	Grade 1 - Systemic intervention not indicated. Grade 2 - Oral intervention indicated Grade 3 - Bronchospasm; hospitalization indicated for clinical sequelae; intravenous intervention indicated Grade 4 - Life-threatening consequences; urgent intervention indicated Grade 5 - Death	Through Day 169
Time-weighted Average (TWA) Daily Change From Baseline in Viral Load (log10 Copies/mL)	Phase 1 Measured by SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples	Day 1 to day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs)	Phase 1	Through Day 169
TEAEs (Treatment-Emergent Adverse Events)	Phase 2 and Phase 3	Through Day 29
Severity of TEAEs (Treatment-Emergent Adverse Event)	Phase 2 and Phase 3	Through Day 29
Percentage of Participants With ISRs (Injection-Site Reactions)	Phase 2 and Phase 3	Through Day 169
Severity of ISRs (Injection-Site Reactions)	Phase 2 and Phase 3	Through Day 169
Percentage of Participants 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
Percentage of Participants With Treatment-emergent SAEs (Serious Adverse Events)	Phase 2 and Phase 3	Through Day 169
Time-weighted Average Change From Baseline in Viral Load	Phase 2 and Phase 3 Time-weighted average (TWA) daily change from baseline in viral load (log10 copies/mL) as measured by SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples.	Through Day 169
Change From Baseline in Viral Load (Phase 1)	Phase 1 Change from baseline in viral load (log10 copies/mL) as measured by SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples.	Through Day 7
Change From Baseline in Viral Load	Phase 2, and Phase 3 As measured by RT-qPCR in NP samples	Through Day 7
Percentage of Participants 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 1	Through Day 169
Concentrations of REGN14256 in Serum Over Time	Phase 2 and Phase 3	Through Day 169
Concentrations of Imdevimab in Serum Over Time (Phase 1)	Phase 1	Through Day 169
Concentrations of Imdevimab in Serum Over Time	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

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2021
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: October 14, 2021
• First Submitted That Met QC Criteria: October 14, 2021
• First Posted (Actual): October 18, 2021

Study Record Updates

• Last Update Posted (Estimated): October 28, 2025
• Last Update Submitted That Met QC Criteria: October 9, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: COVID-19; coronavirus; Symptomatic; Coronavirus disease 2019 (COVID-19); Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2); Non-hospitalized; Low-risk
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronaviridae Infections; Nidovirales Infections; COVID-19; Coronavirus Infections; Anti-Infective Agents; Antiviral Agents; casirivimab and imdevimab drug combination; casirivimab; imdevimab; REGN14256
• Other Study ID Numbers: R14256-COV-2149

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• IPD Sharing Time Frame: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No