COVID-19 Study Assessing the Virologic Efficacy of REGN10933+REGN10987 Across Different Dose Regimens in Adult Outpatients With SARS-CoV-2 Infection

A Phase 2 Study to Assess the Virologic Efficacy of REGN10933+REGN10987 Across Different Dose Regimens in Outpatients With SARS-CoV-2 Infection

The primary objective of the study is to assess the virologic efficacy of REGN10933+REGN10987 across different intravenous and subcutaneous doses compared to placebo.

The secondary objectives of the study are:

• To evaluate additional indicators of virologic efficacy of REGN10933+REGN10987 compared to placebo
• To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo
• To assess the concentrations of REGN10933 and REGN10987 in serum over time
• To assess the immunogenicity of REGN10933 and REGN10987

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: REGN10933+REGN10987 combination therapy; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1149
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Mesa, Arizona, United States, 85210
      • Regeneron Study Site
    • Tucson, Arizona, United States, 85712
      • Regeneron Study Site
  • California
    • Canoga Park, California, United States, 91303
      • Regeneron Study Site
    • Long Beach, California, United States, 90806
      • Regeneron Study Site
    • Los Angeles, California, United States, 90036
      • Regeneron Study Site
    • Rolling Hills Estates, California, United States, 90274
      • Regeneron Study Site
    • San Francisco, California, United States, 94127
      • Regeneron Study Site
    • Santa Monica, California, United States, 90404
      • Regeneron Study Site
    • Stanford, California, United States, 94305
      • Regeneron Study Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Regeneron Study Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • Regeneron Study Site
  • Florida
    • DeLand, Florida, United States, 32720
      • Regeneron Study Site
    • Fort Pierce, Florida, United States, 34982
      • Regeneron Study Site
    • Hialeah, Florida, United States, 33010
      • Regeneron Study Site
    • Hialeah, Florida, United States, 33012
      • Regeneron Study Site
    • Maitland, Florida, United States, 32751
      • Regeneron Study Site
    • Miami, Florida, United States, 33126
      • Regeneron Study Site
    • Miami, Florida, United States, 33184
      • Regeneron Study Site
    • Saint Petersburg, Florida, United States, 33705
      • Regeneron Study Site
    • Tampa, Florida, United States, 33606
      • Regeneron Study Site
    • West Palm Beach, Florida, United States, 33407
      • Regeneron Study Site
    • Winter Haven, Florida, United States, 33880
      • Regeneron Study Site
    • Winter Park, Florida, United States, 32789
      • Regeneron Study Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Regeneron Study Site
    • Columbus, Georgia, United States, 31904
      • Regeneron Study Site
  • Illinois
    • Downers Grove, Illinois, United States, 60515
      • Regeneron Study Site
  • Iowa
    • Ames, Iowa, United States, 50010-3014
      • Regeneron Study Site
    • Iowa City, Iowa, United States, 52242
      • Regeneron Study Site
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Regeneron Study Site
    • Marrero, Louisiana, United States, 70072
      • Regeneron Study Site
    • Shreveport, Louisiana, United States, 71118
      • Regeneron Study Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Regeneron Study Site
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Regeneron Study Site
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Regeneron Study Site
  • New York
    • Bronx, New York, United States, 10451
      • Regeneron Study Site
    • New York, New York, United States, 10037
      • Regeneron Study Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • Regeneron Study Site
    • Durham, North Carolina, United States, 27705
      • Regeneron Study Site
    • Wilmington, North Carolina, United States, 28401
      • Regeneron Study Site
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Regeneron Study Site
    • Dayton, Ohio, United States, 45409
      • Regeneron Study Site
    • Dayton, Ohio, United States, 45432
      • Regeneron Study Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Regeneron Study Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Regeneron Study Site
    • Clinton, South Carolina, United States, 29325
      • Regeneron Study Site
  • Texas
    • Amarillo, Texas, United States, 79109
      • Regeneron Study Site
    • Corpus Christi, Texas, United States, 78413
      • Regeneron Study Site
    • Houston, Texas, United States, 77030
      • Regeneron Study Site
    • Houston, Texas, United States, 77008
      • Regeneron Study Site
    • Houston, Texas, United States, 77057
      • Regeneron Study Site
    • Houston, Texas, United States, 77093
      • Regeneron Study Site
    • Pearland, Texas, United States, 77584
      • Regeneron Study Site
    • Red Oak, Texas, United States, 75154
      • Regeneron Study Site
    • San Antonio, Texas, United States, 78249
      • Regeneron Study Site
    • Splendora, Texas, United States, 77372
      • Regeneron Study Site
    • Tyler, Texas, United States, 75701
      • Regeneron Study Site
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Regeneron Study Site

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Has SARS-CoV-2-positive diagnostic test from a sample collected ≤72 hours prior to randomization, as defined by the protocol

• Low-risk symptomatic patient: Has symptoms consistent with COVID-19 (as determined by the investigator) with onset ≤7 days before randomization, and meets all of the following 8 criteria:

  1. Age ≤50
  2. No obesity, with obesity defined as BMI ≥30 kg/m2
  3. Does not have cardiovascular disease or hypertension
  4. Does not have chronic lung disease or asthma
  5. Does not have type 1 or type 2 diabetes mellitus
  6. Does not have chronic kidney disease, with or without dialysis
  7. Does not have chronic liver disease
  8. Is not pregnant or
• Asymptomatic patient: Has had no symptoms consistent with COVID-19 (as determined by the investigator) occurring at any time <2 months prior to randomization
• Maintains O2 saturation ≥93% on room air

Key Exclusion Criteria:

• Was admitted to a hospital for COVID-19 prior to randomization, or is hospitalized (inpatient) for any reason at randomization
• Has a known 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
• Is immunosuppressed, based on investigator's assessment
• 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 planned future use of any of the following treatments: COVID-19 convalescent plasma, mAbs against SARS-CoV-2, (eg, bamlanivimab), IVIG (any indication), systemic corticosteroids (any indication), or COVID-19 treatments (authorized, approved, or investigational)
• Prior use (prior to randomization), current use (at randomization), or planned use (within time period given per CDC guidance but no sooner than 22 days of study drug administration) of any authorized or approved vaccine for COVID-19
• Has known active infection with influenza or other non-SARS-CoV-2 respiratory pathogen, confirmed by a diagnostic test
• Has participated, is participating, or plans to participate in a clinical research study evaluating any authorized, approved, or investigational vaccine for COVID-19

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

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IV Dose 1; Combination therapy intravenous (IV) single dose	Drug: REGN10933+REGN10987 combination therapy; Administered IV or SC single dose; Other Names: REGN-COV2; REGEN-COV™; Ronapreve™; casirivimab; imdevimab
Experimental: IV Dose 2; Combination therapy IV single dose	Drug: REGN10933+REGN10987 combination therapy; Administered IV or SC single dose; Other Names: REGN-COV2; REGEN-COV™; Ronapreve™; casirivimab; imdevimab
Experimental: IV Dose 3; Combination therapy IV single dose	Drug: REGN10933+REGN10987 combination therapy; Administered IV or SC single dose; Other Names: REGN-COV2; REGEN-COV™; Ronapreve™; casirivimab; imdevimab
Experimental: IV Dose 4; Combination therapy IV single dose	Drug: REGN10933+REGN10987 combination therapy; Administered IV or SC single dose; Other Names: REGN-COV2; REGEN-COV™; Ronapreve™; casirivimab; imdevimab
Experimental: Placebo IV Dose; Matching placebo IV single dose	Drug: Placebo; Administered IV or SC single dose to match
Experimental: SC Dose 1; Combination therapy subcutaneous (SC) single dose	Drug: REGN10933+REGN10987 combination therapy; Administered IV or SC single dose; Other Names: REGN-COV2; REGEN-COV™; Ronapreve™; casirivimab; imdevimab
Experimental: SC Dose 2; Combination therapy SC single dose	Drug: REGN10933+REGN10987 combination therapy; Administered IV or SC single dose; Other Names: REGN-COV2; REGEN-COV™; Ronapreve™; casirivimab; imdevimab
Experimental: Placebo SC Dose; Matching placebo SC single dose	Drug: Placebo; Administered IV or SC single dose to match

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-Weighted Average Daily Change From Day 1 in Viral Load in NP Swab Samples	Time-weighted average daily change from Day 1 in viral load (log10 copies/mL), as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples.	Day 1 to Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-Weighted Average Daily Change From Day 1 in Viral Load	Time-weighted average daily change from Day 1 in viral load (log10 copies/mL) as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples.	Day 1 to Day 5
Time-Weighted Average Daily Change From Day 1 in Viral Load in Participants With High Viral Load at Baseline	Time-weighted average daily change from Day 1 in viral load (log10 copies/mL) as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples. in any participant with a viral load greater than 10,000 copies/mL at baseline.	Day 1 to Day 7
Time-Weighted Average Daily Change From Day 1 in Viral Load in Participants With High Viral Load at Baseline	Time-weighted average daily change from Day 1 in viral load (log10 copies/mL) as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples. in any participant with a viral load greater than 10,000 copies/mL at baseline.	Day 1 to Day 5
Number of Participants With High Viral Load	Number of participants with viral load greater than 10,000 copies/mL, as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples.	Day 1, Day 3, Day 5, Day 7, Day 15, Day 22
Number of Participants With Viral Loads Below the Limit of Detection	Number of participants with viral load less than 299 copies/mL, as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples.	Day 1, Day 3, Day 5, Day 7, Day 15, Day 22
Number of Participants With Viral Loads Below the Lower Limit of Quantification	Number of participants with viral load less than 714 copies/mL, as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples.	Day 1, Day 3, Day 5, Day 7, Day 15, Day 22
Change From Day 1 in Viral Load as Measured by RT-qPCR in NP Swab Samples	Change from Day 1 in Viral Load (log10 copies/mL) as Measured by Quantitative reverse transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) Swab Samples	Day 3, Day 5, Day 7, Day 15, Day 22
Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs)		Through day 29
Number of Participants With Infusion-Related Reactions Grade 2 or Above		Through day 4
Number of Participants With Injection-Site Reactions Grade 3 or Above		Through day 4
Number of Participants With Hypersensitivity Reactions Grade 2 or Above		Through day 29
Concentration of REGN10933 in Serum		Pre-Dose, 15 minutes Post-Dose, 3 days Post-Dose, 5 days Post-Dose, 7 days Post-Dose, 120 days Post-Dose
Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10933		Through day 120
Immunogenicity as Measured by Neutralizing Anti-drug Antibody (NAb) to REGN10933		Through day 120
Concentration of REGN10987 in Serum		Pre-Dose, 15 minutes Post-Dose, 3 days Post-Dose, 5 days Post-Dose, 7 days Post-Dose, 120 days Post-Dose
Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10987		Through day 120
Immunogenicity as Measured by Neutralizing Anti-drug Antibody (NAb) to REGN10987		Through day 120

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.
• Portal-Celhay C, Forleo-Neto E, Eagan W, Musser BJ, Davis JD, Turner KC, Norton T, Hooper AT, Hamilton JD, Pan C, Mahmood A, Baum A, Kyratsous CA, Kim Y, Parrino J, Kampman W, Roque-Guerrero L, Stoici R, Fatakia A, Soo Y, Geba GP, Kowal B, DiCioccio AT, Stahl N, Lipsich L, Braunstein N, Herman GA, Yancopoulos GD, Weinreich DM; COVID-19 Phase 2 Dose-Ranging Study Team. Virologic Efficacy of Casirivimab and Imdevimab COVID-19 Antibody Combination in Outpatients With SARS-CoV-2 Infection: A Phase 2 Dose-Ranging Randomized Clinical Trial. JAMA Netw Open. 2022 Aug 1;5(8):e2225411. doi: 10.1001/jamanetworkopen.2022.25411.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2020
• Primary Completion (Actual): March 4, 2021
• Study Completion (Actual): September 21, 2021

Study Registration Dates

• First Submitted: December 10, 2020
• First Submitted That Met QC Criteria: December 10, 2020
• First Posted (Actual): December 14, 2020

Study Record Updates

• Last Update Posted (Actual): April 8, 2022
• Last Update Submitted That Met QC Criteria: March 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Coronavirus disease 2019 (COVID-19); Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) coronavirus; Non-hospitalized
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: R10933-10987-COV-20145

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; 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