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

NCT05081388 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: R14256-COV-2149
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 28

Brief Summary

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

Conditions

SARS-CoV-2

Keywords

COVID-19; Non-hospitalized; Low-risk; Symptomatic; Coronavirus disease 2019 (COVID-19); Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2); coronavirus

Outcome Measures

Primary Outcomes (7)

• 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. 1. \- Mild; Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated 2. \- Moderate; Minimal, local, or noninvasive intervention indicated; limiting age appropriate instrumental activities of daily living (ADL) 3. \- Severe; Severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; ADL2 limiting self-care 4. \- Life-threatening; Life threatening consequences; urgent intervention indicated 5. \- 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 Outcomes (18)

• Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs)

  Through Day 169

• TEAEs (Treatment-Emergent Adverse Events)

  Through Day 29

• Severity of TEAEs (Treatment-Emergent Adverse Event)

  Through Day 29

• Percentage of Participants With ISRs (Injection-Site Reactions)

  Through Day 169

• Severity of ISRs (Injection-Site Reactions)

  Through Day 169

Study Arms (5)

REGN14256 + imdevimab

EXPERIMENTAL

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; Drug: imdevimab

REGN14256

EXPERIMENTAL

Phase 1, Phase 2: Randomized 1:1:1:1:1

Drug: REGN14256

Imdevimab

EXPERIMENTAL

Phase 1, Phase 2: Randomized 1:1:1:1:1

Drug: imdevimab

casirivimab + imdevimab

EXPERIMENTAL

Phase 1, Phase 2: Randomized 1:1:1:1:1 Phase 3: (≥18 Years): Randomized 1:1:1

Drug: imdevimab; Drug: casirivimab + imdevimab

Placebo

EXPERIMENTAL

Phase 1, Phase 2: Randomized 1:1:1:1:1 Phase 3: (≥18 Years): Randomized 1:1:1

Drug: Placebo

Interventions

REGN14256 DRUG

Sub-cutaneous (SC) single dose

REGN14256; REGN14256 + imdevimab

imdevimab DRUG

SC single dose

Also known as: REGN10987

Imdevimab; REGN14256 + imdevimab; casirivimab + imdevimab

casirivimab + imdevimab DRUG

SC single dose

Also known as: REGN10933 + REGN10987, REGN-COV2, REGEN-COV™, Ronapreve™

casirivimab + imdevimab

Placebo DRUG

SC single dose

Placebo

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Maintains O2 saturation ≥93% on room air
• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (28)

Regeneron Research Site

La Mesa, California, 91941, United States

Location

Ark Clinical Research

Long Beach, California, 90806, United States

Location

PNS Clinical Research, LLC

Mission Viejo, California, 92691, United States

Location

Regeneron Research Site

Ft. Pierce, Florida, 34982, United States

Location

AGA Clinical Trials

Hialeah, Florida, 33012, United States

Location

Regeneron Research Site

Loxahatchee Groves, Florida, 33470, United States

Location

Project 4 Research, Inc.

Miami, Florida, 33125, United States

Location

Universal Medical and Research Center, LLC

Miami, Florida, 33126, United States

Location

Global Medical Trials

Miami, Florida, 33174, United States

Location

Bio-Medical Research LLC

Miami, Florida, 33184, United States

Location

Charisma Research and Medical Center

Miami Lakes, Florida, 33014, United States

Location

Triple O Research Institute, P.A.

West Palm Beach, Florida, 33407, United States

Location

Regeneron Research Site

Winter Park, Florida, 32789, United States

Location

IACT Health

Columbus, Georgia, 31904, United States

Location

Chicago Clinical Research Institute

Chicago, Illinois, 60607, United States

Location

Regeneron Research Site

Ames, Iowa, 50010, United States

Location

Regeneron Research Site

Marrero, Louisiana, 70072, United States

Location

Olive Branch Family Medical Center

Olive Branch, Mississippi, 38654, United States

Location

Forte Family Practice

Las Vegas, Nevada, 89103, United States

Location

New York Health and Hospitals / Lincoln

The Bronx, New York, 10451, United States

Location

NYC H+H / Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

Regeneron Research Site

Wilmington, North Carolina, 28401, United States

Location

Regeneron Research Site

Dayton, Ohio, 45409, United States

Location

Carolina Medical Research

Clinton, South Carolina, 29325, United States

Location

PharmaTex Research, LLC

Amarillo, Texas, 79109, United States

Location

Advanced Diagnostics Clinic, River Oaks Hospital and Clinics

Houston, Texas, 77027, United States

Location

Regeneron Research Site

Houston, Texas, 77030, United States

Location

Regeneron Research Site

Houston, Texas, 77093, United States

Location

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

REGN14256; imdevimab; casirivimab and imdevimab drug combination; casirivimab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Due to the reduced activity of REGN14256+Imdevimab against the emerging Omicron variant and not due to any safety concerns, study enrollment was paused and later terminated in the phase 1 portion of the study. Phase 2 and phase 3 portions of the study were never opened. As a result, and due to small sample size, not all of the original objectives and endpoints were analyzed as planned

Results Point of Contact

• Title: Clinical Trials Administrator
• Organization: Regeneron Pharmaceuticals, Inc.

clinicaltrials@regeneron.com

8447346643

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase1/Phase2/Phase3

Study Record Dates

• First Submitted: October 14, 2021
• First Posted: October 18, 2021
• Study Start: November 8, 2021
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2022
• Last Updated: October 28, 2025
• Results First Posted: April 26, 2024

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• 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.
• 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

Locations

US (28)