Study Assessing the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Repeated Subcutaneous Doses of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies (REGN10933+REGN10987) in Adult Volunteers as Related to COVID-19

A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study Assessing the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Repeated Subcutaneous Doses of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies (REGN10933+REGN10987) in Adult Volunteers

The primary objectives are:

• To assess the occurrence of adverse events of special interest (AESIs) in participants treated with repeated subcutaneous (SC) doses of REGN10933+REGN10987 compared to placebo
• To assess the concentrations of REGN10933 and REGN10987 in serum over time after single and repeated SC administration

The secondary objectives are:

• To assess the safety and tolerability of repeated SC doses of REGN10933+REGN10987 compared to placebo
• To assess attainment of target concentrations of REGN10933 and REGN10987 in serum after single and repeated SC administration
• To assess the immunogenicity of REGN10933 and REGN10987

Study Overview

• Status: Completed
• Conditions: Healthy; Chronic Stable Illness
• Intervention / Treatment: Drug: REGN10933+REGN10987; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 974
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Regeneron Study Site
  • Arkansas
    • Rogers, Arkansas, United States, 72758
      • Regeneron Study Site
  • California
    • Sacramento, California, United States, 95864
      • Regeneron Study Site
  • Florida
    • Miami, Florida, United States, 33014
      • Regeneron Study Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Regeneron Study Site
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Regeneron Study Site
  • Texas
    • Austin, Texas, United States, 78705
      • Regeneron Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Is healthy or has chronic medical condition(s) that is stable and well controlled as per the opinion of the investigator and is not likely to require medical intervention through the end of study
2. Stable medication for co-morbid condition(s) for at least 6 months prior to screening
3. Willing and able to comply with study visits and study-related procedures, including compliance with site precautionary requirements related to SARS-CoV-2 infection and transmission

Key Exclusion Criteria:

1. Positive diagnostic test for SARS-CoV-2 infection ≤72 hours prior to randomization
2. Subject-reported clinical history of COVID-19 as determined by investigator
3. Subject-reported history of prior positive diagnostic test for SARS-CoV-2 infection
4. Active respiratory or non-respiratory symptoms suggestive or consistent with COVID-19
5. Medically attended acute illness, systemic antibiotics use, or hospitalization (ie, >24 hours) for any reason within 30 days prior to screening
6. Acute exacerbation of a chronic pulmonary condition (eg, chronic obstructive pulmonary disease [COPD], asthma exacerbations) in the past 6 months prior to screening
7. Received investigational or approved SARS-CoV-2 vaccine
8. Received investigational or approved passive antibodies for SARS-CoV-2 infection prophylaxis as defined in the protocol
9. Use of remdesivir, intravenous immunoglobulin (IVIG), or other anti-SARS viral agents within 2 months prior to screening

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Administered subcutaneous (SC) every 4 weeks (Q4W)
Experimental: REGN10933+REGN10987	Drug: REGN10933+REGN10987; Administered subcutaneous (SC) every 4 weeks (Q4W); Other Names: REGN-COV2; Casirivimab; Imdevimab; REGEN-COV™; Ronapreve™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration	Within 4 days postdose at Baseline
Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration	Within 4 days postdose at Day 29
Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration	Within 4 days postdose at Day 57
Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration	Within 4 days postdose at Day 85
Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration	Within 4 days postdose at Day 113
Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration	Within 4 days postdose at Day 141
Concentrations of REGN10933 in serum over time	Up to 52 weeks
Concentrations of REGN10987 in serum over time	Up to 52 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of participants with treatment-emergent adverse events (TEAEs)	Up to 52 weeks
Severity of TEAEs	Up to 52 weeks
Proportion of participants who achieve or exceed target concentration in serum of REGN10933	Up to 52 weeks
Proportion of participants who achieve or exceed target concentration in serum of REGN10987	Up to 52 weeks
Immunogenicity as measured by anti-drug antibodies (ADA) to REGN10933	Up to 52 weeks
Immunogenicity as measured by anti-drug antibodies (ADA) to REGN10987	Up to 52 weeks

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
• Hirsch C, Park YS, Piechotta V, Chai KL, Estcourt LJ, Monsef I, Salomon S, Wood EM, So-Osman C, McQuilten Z, Spinner CD, Malin JJ, Stegemann M, Skoetz N, Kreuzberger N. SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19. Cochrane Database Syst Rev. 2022 Jun 17;6(6):CD014945. doi: 10.1002/14651858.CD014945.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2020
• Primary Completion (Actual): November 22, 2021
• Study Completion (Actual): November 22, 2021

Study Registration Dates

• First Submitted: July 24, 2020
• First Submitted That Met QC Criteria: August 18, 2020
• First Posted (Actual): August 19, 2020

Study Record Updates

• Last Update Posted (Actual): January 26, 2022
• Last Update Submitted That Met QC Criteria: January 10, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Coronavirus disease 2019 (COVID-19); Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2)
• Other Study ID Numbers: R10933-10987-HV-2093

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: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data 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 the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

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