A Study to Evaluate Efficacy and Safety of Casirivimab+Imdevimab (Monoclonal Antibodies) for Prevention of COVID-19 in Immunocompromised Adolescents and Adults

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Anti-Spike SARS-CoV-2 Monoclonal Antibodies as Pre-Exposure Prophylaxis to Prevent COVID-19 in Immunocompromised Participants

The primary objective of the study is to evaluate the effect of casirivimab+imdevimab, compared with placebo, in preventing symptomatic SARS-CoV-2 infection in immunocompromised participants.

The secondary objectives of the study are:

• To evaluate the safety and tolerability of repeated SC injections of casirivimab+imdevimab in the study population
• To characterize concentrations of casirivimab and imdevimab in serum over time
• To assess the immunogenicity of casirivimab and imdevimab

Study Overview

• Status: Terminated
• Conditions: Immunocompromised
• Intervention / Treatment: Drug: Placebo; Drug: casirivimab+imdevimab

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 3

Contacts and Locations

Study Locations

• Mexico
  • Mexico City
    • Cuauhtémoc, Mexico City, Mexico, 6700
      • Regeneron Study Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Central Alabama Research
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Baptist Health Center for Clinical Research
  • California
    • Long Beach, California, United States, 90806
      • Regeneron Study Site
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90033
      • Regeneron Study Site
    • Palo Alto, California, United States, 94304
      • Stanford University
    • Sacramento, California, United States, 95817
      • University of California
    • Stanford, California, United States, 94305
      • Regeneron Study Site
    • West Hollywood, California, United States, 90069
      • James R Berenson MD Inc.
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Connecticut
    • North Haven, Connecticut, United States, 06473-2195
      • Regeneron Study Site
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Georgetown University
  • Florida
    • Aventura, Florida, United States, 33180
      • Arthritis and Rheumatic Disease Specialties
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida, Inc.
    • Ft. Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center
    • Hollywood, Florida, United States, 33024
      • Elixia COVID-19
    • Miami, Florida, United States, 33184
      • De La Cruz Research Center, LLC
    • Miami, Florida, United States, 33126
      • AppleMed Research Group, LLC
    • Tampa, Florida, United States, 33606
      • University of South Florida
    • Zephyrhills, Florida, United States, 33542
      • Florida Medical Clinic, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Regeneron Study Site
    • Marietta, Georgia, United States, 30060
      • Regeneron Study Site
  • Illinois
    • Chicago, Illinois, United States, 60625
      • Great Lakes Clinical Trials - Ravenswood
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
    • Baltimore, Maryland, United States, 21201
      • Institute of Human Virology
    • Bethesda, Maryland, United States, 20892
      • Laboratory of Clinical Immunology and Microbiology, NIAID
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02115
      • Regeneron Study Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Jersey
    • Neptune City, New Jersey, United States, 07753
      • Jersey Shore University Medical Center
    • Teaneck, New Jersey, United States, 07666
      • Holy Name
  • New York
    • Brooklyn, New York, United States, 11220
      • Maimonides Cancer Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10032-3729
      • Regeneron Study Site
    • New York, New York, United States, 10065
      • Regeneron Study Site 2
    • Rochester, New York, United States, 14642
      • Regeneron Study Site
    • Syracuse, New York, United States, 13215
      • SUNY Upstate Medical University
    • Syracuse, New York, United States, 13210
      • Regeneron Study Site
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • North Carolina
    • Morganton, North Carolina, United States, 28655
      • Burke Primary Care
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center Research
    • Cleveland, Ohio, United States, 44195
      • Regeneron Study Site
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center For Clinical Research
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Prevention Clinical Research Site
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Regeneron Study Site
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • West Tennessee Research Institute
  • Texas
    • Amarillo, Texas, United States, 79109
      • PharmaTex Research, LLC
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • Houston, Texas, United States, 77030
      • Md Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts, PA
    • Houston, Texas, United States, 77087
      • Synergy Group Medical,LLC
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Regeneron Study Site
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center- First Hill
    • Seattle, Washington, United States, 98109
      • Regeneron Study Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin - Madison

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Meets ≥1 of the following criteria:

   • Is immunocompromised, including people with transplant, who have cancer, primary immunodeficiencies, HIV, rheumatological disease, autoimmune disease, multiple sclerosis OR
   • Currently taking immunosuppressant drugs
2. Have been fully vaccinated against COVID-19 or deemed medically ineligible to receive full course of vaccine
3. Has documented negative serology/antibody response in an anti-SARS-CoV-2 spike protein IgG clinical test or ≤50 U/mL on the Elecsys® SARS-CoV-2 S Total Ig test
4. Tested negative for the COVID-19 virus within 72 hours prior to randomization

Key Exclusion Criteria:

1. Weighs <40 kg (only applies to participants ≥12 to <18 years of age)
2. Has any signs or symptoms consistent with COVID-19
3. Past COVID-19 infection within 90 days prior to randomization
4. Planned use of any investigational, authorized, or approved vaccine for COVID-19 within 90 days of the last dose of study drug
5. Prior, current, or planned use of any of COVID-19 convalescent plasma, other monoclonal antibodies against SARS-CoV-2 or any COVID-19 treatment
6. Is planned to begin immunoglobulin (IVIG) or immunoglobulin (SCIG) therapy, is planned to have a change to existing IVIG or SCIG, or has been on a chronic stable dose of their IVIG or SCIG regimen for less than 90 days prior to screening
7. Has any known active acute respiratory infection
8. Has persistent (refractory to treatment for ≥14 days) bacterial or fungal infection
9. Has known allergy or hypersensitivity to components of the study drugs

NOTE: Other Protocol Defined Inclusion/Exclusion Criteria Apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: casirivimab+imdevimab Initial + Q4W; Initial subcutaneous (SC) dose, then SC dose every 4 weeks (Q4W)	Drug: casirivimab+imdevimab; Co-administered sequentially subcutaneous (SC); Other Names: REGN-COV2; REGEN-COV™; Ronapreve™; REGN10933; REGN10987
Experimental: casirivimab+imdevimab Q4W; SC dose Q4W	Drug: casirivimab+imdevimab; Co-administered sequentially subcutaneous (SC); Other Names: REGN-COV2; REGEN-COV™; Ronapreve™; REGN10933; REGN10987
Experimental: casirivimab+imdevimab Q12W; SC dose every 12 weeks (Q12W)	Drug: casirivimab+imdevimab; Co-administered sequentially subcutaneous (SC); Other Names: REGN-COV2; REGEN-COV™; Ronapreve™; REGN10933; REGN10987
Placebo Comparator: Placebo; SC dose Q4W	Drug: Placebo; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Incidence of Symptomatic (Broad Term), RT-PCR-confirmed SARS-CoV-2 Infection Cases During the EAP	Cumulative incidence of symptomatic (broad term), RT-PCR-confirmed SARS-CoV-2 infection cases during the Efficacy Assessment Period (EAP)	The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Grade ≥3 Treatment-emergent Adverse Events (TEAEs) During the EAP	The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days
Number of Participants With Grade ≥3 Treatment-emergent Adverse Events (TEAEs) During the Follow-Up Period	End of EAP to the end of the Follow-Up Period (Day 169 to 205, approximately ~1 months)
Number of Participants With TEAEs Leading to Study Drug Discontinuation During the EAP	The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days
Number of Participants With TEAEs Leading to Study Drug Discontinuation During the Follow-Up Period	End of EAP to the end of the Follow-Up Period (Day 169 to 205, approximately ~1 months)
Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the EAP	The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days
Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the Follow-Up Period	End of EAP to the end of the Follow-Up Period (Day 169 to 205, approximately ~1 months)
Incidence of Adverse Events of Special Interest (AESIs) During the EAP	The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days
Concentration of Casirivimab Over Time	Up to 28 days postdose for the Q4W groups and 84 days postdose for the Q12 group
Concentration of Imdevimab Over Time	Up to 28 days postdose for the Q4W groups and 84 days postdose for the Q12 group
Incidence of Anti-drug Antibodies (ADA) Over Time	Up to 28 days postdose for the Q4W groups and 84 days postdose for the Q12 group
Incidence of Neutralizing Antibodies (NAb) to Each mAb Over Time	Up to 28 days postdose for the Q4W groups and 84 days postdose for the Q12 group

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2021
• Primary Completion (Actual): May 18, 2022
• Study Completion (Actual): May 18, 2022

Study Registration Dates

• First Submitted: October 8, 2021
• First Submitted That Met QC Criteria: October 8, 2021
• First Posted (Actual): October 12, 2021

Study Record Updates

• Last Update Posted (Actual): October 20, 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; Non-response to COVID-19 vaccination; Immunocompromised, weakened immune system
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Anti-Infective Agents; Antiviral Agents; casirivimab and imdevimab drug combination; casirivimab; imdevimab
• Other Study ID Numbers: R10933-10987-COV-2176; 2021-005222-14 (EudraCT Number)

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