Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Adult and Pediatric Patients With COVID-19

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04425629
Recruitment Status : Recruiting
First Posted : June 11, 2020
Last Update Posted : April 5, 2021
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE June 8, 2020
First Posted Date  ICMJE June 11, 2020
Last Update Posted Date April 5, 2021
Actual Study Start Date  ICMJE June 16, 2020
Estimated Primary Completion Date April 10, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 31, 2021)
  • Proportion of patients with treatment-emergent serious adverse events (SAEs) [ Time Frame: Through Day 29 ]
    Primary: Phase 1, Phase 3 (Cohort 2 and Cohort 3) Secondary: Phase 2, Phase 3 (Cohort 1)
  • Proportion of patients with infusion-related reactions [ Time Frame: Through Day 4 ]
    Primary: Phase 1, Phase 3 (Cohort 2 and Cohort 3) Secondary: Phase 2, Phase 3 (Cohort 1)
  • Proportion of patients with hypersensitivity reactions [ Time Frame: Through Day 29 ]
    Primary: Phase 1, Phase 3 (Cohort 2 and Cohort 3) Secondary: Phase 2, Phase 3 (Cohort 1)
  • Time-weighted average change from baseline in viral load (log10 copies/mL), as measured by quantitative reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples [ Time Frame: Baseline up to Day 7 ]
    Primary: Phase 1, Phase 2 Secondary: Phase 3 (Cohort 1, for patients enrolled prior to protocol amendment 6 only), Phase 3 (Cohort 2)
  • Proportion of patients with at least one (≥1) COVID-19-related hospitalization or all-cause death [ Time Frame: Through Day 29 ]
    Primary: Phase 3 (Cohort 1) Secondary: Phase 3 (Cohort 2)
  • Concentration of REGN10933 in serum over time [ Time Frame: Through Day 29 ]
    Primary: Phase 3 (Cohort 2) Secondary: Phase 1, Phase 2, Phase 3 (Cohort 1, Cohort 2 and Cohort 3)
  • Concentration of REGN10987 in serum over time [ Time Frame: Through Day 29 ]
    Primary: Phase 3 (Cohort 2) Secondary: Phase 1, Phase 2, Phase 3 (Cohort 1, Cohort 2 and Cohort 3)
Original Primary Outcome Measures  ICMJE
 (submitted: June 8, 2020)
  • Proportion of patients with treatment-emergent serious adverse events (SAEs) [ Time Frame: Through Day 29 ]
    Primary: Phase 1 Secondary: Phase 2, Phase 3
  • Proportion of patients with infusion-related reactions [ Time Frame: Through Day 4 ]
    Primary: Phase 1 Secondary: Phase 2, Phase 3
  • Proportion of patients with hypersensitivity reactions [ Time Frame: Through Day 29 ]
    Primary: Phase 1 Secondary: Phase 2, Phase 3
  • Time-weighted average change from baseline in viral shedding as measured by quantitative reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples [ Time Frame: Baseline up to Day 22 ]
    Phase 1 only
  • Time-weighted average change from baseline in viral shedding as measured by RT-qPCR in saliva samples [ Time Frame: Baseline up to Day 22 ]
    Primary: Phase 2 Secondary: Phase 1, Phase 3
  • Proportion of patients with at least one COVID-19 related medically attended visit [ Time Frame: Through Day 29 ]
    Primary: Phase 3 Secondary: Phase 1, Phase 2
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 31, 2021)
  • Time-weighted average change from baseline in viral load (log10 copies/mL), as measured by RT-qPCR in saliva samples [ Time Frame: Baseline up to Day 22 ]
    Phase 1 Only
  • Time-weighted average change from baseline in viral load (log10 copies/mL), as measured by RT-qPCR in nasal swab samples [ Time Frame: Baseline up to Day 22 ]
    Phase 1 Only
  • Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR in any tested samples [ Time Frame: Through Day 29 ]
    Phase 1 Only
  • Time to negative RT-qPCR in nasopharyngeal swabs with no subsequent positive RT-qPCR [ Time Frame: Through Day 29 ]
    Phase 2 Only
  • Change from baseline in viral load at each visit, as measured by RT-qPCR in nasopharyngeal swabs [ Time Frame: Baseline up to Day 29 ]
    Phase 1, Phase 2, Phase 3 (Cohort 1 and Cohort 2)
  • Change from baseline in viral load at each visit, as measured by RT-qPCR in saliva samples [ Time Frame: Baseline up to Day 29 ]
    Phase 1 Only
  • Change from baseline in viral load at each visit, as measured by RT-qPCR in nasal swabs [ Time Frame: Baseline up to Day 29 ]
    Phase 1 Only
  • Correlation of RT-qPCR results over time between different sample types (NP, nasal, and saliva) [ Time Frame: Up to Day 29 ]
    Phase 1 Only
  • Concordance of RT-qPCR results over time between different sample types (NP, nasal, and saliva) [ Time Frame: Up to Day 29 ]
    Phase 1 Only
  • Time-weighted average change from baseline in viral load (log10 copies/mL) from day 1 to post-baseline study days [ Time Frame: Day 1 to Day 29 ]
    Phase 1, Phase 2
  • Proportion of participants with ≥1 COVID-19-related medically-attended visit [ Time Frame: Through Day 29 ]
    Phase 1, Phase 2
  • Proportion of participants with ≥2 COVID-19-related medically-attended visit [ Time Frame: Through Day 29 ]
    Phase 1, Phase 2, Phase 3 (Cohort 1 and Cohort 2)
  • Total number of COVID-19-related medically-attended visits [ Time Frame: Through Day 29 ]
    Phase 1, Phase 2, Phase 3 (Cohort 1 and Cohort 2)
  • Proportion of participants admitted to a hospital due to COVID-19 [ Time Frame: Through Day 29 ]
    Phase 1, Phase 2
  • Proportion of participants with ≥1 outpatient or telemedicine visit due to COVID-19 [ Time Frame: Through Day 29 ]
    Phase 1, Phase 2
  • Assessment of pharmacokinetic (PK) parameter: maximum serum concentration observed (Cmax) of REGN10933 [ Time Frame: Through Day 29 ]
    Phase 1 Only
  • Assessment of PK parameter: maximum serum concentration observed (Cmax) of REGN10987 [ Time Frame: Through Day 29 ]
    Phase 1 Only
  • Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) of REGN10933 [ Time Frame: Through Day 29 ]
    Phase 1 Only
  • Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) of REGN10987 [ Time Frame: Through Day 29 ]
    Phase 1 Only
  • Assessment of PK parameter: Time to Cmax (tmax) for REGN10933 [ Time Frame: Through Day 29 ]
    Phase 1 Only
  • Assessment of PK parameter: Time to Cmax (tmax) for REGN10987 [ Time Frame: Through Day 29 ]
    Phase 1 Only
  • Assessment of PK parameter: Area Under the Curve (AUC) computed from time zero to the time of the last positive concentration (AUClast) for REGN10933 [ Time Frame: Through Day 29 ]
    Phase 1 Only
  • Assessment of PK parameter: AUC computed from time zero to the time of the last positive concentration (AUClast) for REGN10987 [ Time Frame: Through Day 29 ]
    Phase 1 Only
  • Immunogenicity as measured by anti-drug (ADA) to REGN10933 [ Time Frame: Through Day 29 ]
    Phase 1, Phase 2, Phase 3 (Cohort 1, Cohort 2 and Cohort 3)
  • Immunogenicity as measured by ADA to REGN10987 [ Time Frame: Through Day 29 ]
    Phase 1, Phase 2, Phase 3 (Cohort 1, Cohort 2 and Cohort 3)
  • Immunogenicity as measured by neutralizing antibodies (NAbs) to REGN10933 [ Time Frame: Through Day 29 ]
    Phase 2, Phase 3 (Cohort 1, Cohort 2 and Cohort 3)
  • Immunogenicity as measured by NAbs to REGN10987 [ Time Frame: Through Day 29 ]
    Phase 2, Phase 3 (Cohort 1, Cohort 2 and Cohort 3)
  • Proportion of participants with high viral load at each visit [ Time Frame: Through Day 29 ]
    Phase 2 Only
  • Proportion of participants with viral loads below the limit of detection at each visit [ Time Frame: Through Day 29 ]
    Phase 2 Only
  • Proportion of participants with viral loads below the lower limit of quantitation at each visit [ Time Frame: Through Day 29 ]
    Phase 2 Only
  • Proportion of participants admitted to an intensive care unit (ICU) due to COVID-19 [ Time Frame: Through Day 29 ]
    Phase 2, Phase 3 (Cohort 1 and Cohort 2)
  • Proportion of participants requiring mechanical ventilation due to COVID-19 [ Time Frame: Through Day 29 ]
    Phase 2, Phase 3 (Cohort 1 and Cohort 2)
  • Number of days of hospitalization due to COVID-19 [ Time Frame: Through Day 29 ]
    Phase 2, Phase 3 (Cohort 1 and Cohort 2)
  • Proportion of participants with all-cause mortality [ Time Frame: Through Day 29 ]
    Phase 2 Only
  • Time to first onset of symptoms consistent with COVID-19 (asymptomatic cohort only) [ Time Frame: Up to Day 29 ]
    Phase 2 Only
  • Duration of symptoms consistent with COVID-19 [ Time Frame: Up to Day 29 ]
    Phase 2 Only
  • Proportion of participants with ≥1 COVID-19-related hospitalization or all-cause death [ Time Frame: From Day 4 Through Day 29 ]
    Phase 3 (Cohort 1 and Cohort 2)
  • Time to COVID-19 symptoms resolution [ Time Frame: Through Day 29 ]
    Phase 3 (Cohort 1)
  • Proportion of participants with ≥1 COVID-19-related hospitalization, emergency room visit, or all-cause death [ Time Frame: Through day 29 ]
    Phase 3 (Cohort 1 and Cohort 2)
  • Proportion of patients with (≥1) COVID-19-related medically-attended visit or all-cause death [ Time Frame: Through Day 29 ]
    Phase 3 (Cohort 1 and Cohort 2)
  • Proportion of participants with ≥1 COVID-19-related medically-attended visit by type of visit [ Time Frame: Through day 29 ]
    Phase 3 (Cohort 1 and Cohort 2) Type of visit defined as hospitalization, emergency room, urgent care, and/or physician's office/telemedicine
  • Cumulative incidence of patients with ≥1 COVID-19-related hospitalization or all-cause death [ Time Frame: Through Day 29 ]
    Phase 3 (Cohort 1 and Cohort 2)
  • Cumulative incidence of patients with ≥1 COVID-19-related hospitalization, emergency room visit, or all-cause death [ Time Frame: Through Day 29 ]
    Phase 3 (Cohort 1 and Cohort 2)
  • Cumulative incidence of patients with ≥1 COVID-19-related medically-attended visit or all-cause death [ Time Frame: Through Day 29 ]
    Phase 3 (Cohort 1 and Cohort 2)
  • Proportion of participants requiring supplemental oxygen due to COVID-19 [ Time Frame: Through Day 29 ]
    Phase 3 (Cohort 1 and Cohort 2)
  • Time to all-cause death [ Time Frame: Through Day 169 ]
    Phase 3 (Cohort 1 and Cohort 2)
  • All-cause death [ Time Frame: By Day 29, Day 120, and Day 169 ]
    Phase 3 (Cohort 1 and Cohort 2)
Original Secondary Outcome Measures  ICMJE
 (submitted: June 8, 2020)
  • Time-weighted average change from baseline in viral shedding measured by RT-qPCR in nasal swab samples [ Time Frame: Baseline up to Day 22 ]
  • Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR in any tested samples [ Time Frame: Through Day 29 ]
  • Change from baseline in Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral shedding as measured by RT-qPCR in NP swabs [ Time Frame: Baseline up to Day 29 ]
    Phase 1 only
  • Change from baseline in SARS-CoV-2 viral shedding as measured by RT-qPCR in saliva samples [ Time Frame: Baseline up to Day 29 ]
  • Change from baseline in SARS-CoV-2 viral shedding as measured by RT-qPCR in nasal swabs [ Time Frame: Baseline up to Day 29 ]
  • Proportion of patients with at least two COVID-19 related medically attended visits [ Time Frame: Through Day 29 ]
  • Total number of COVID-19-related medically-attended visits [ Time Frame: Through Day 29 ]
  • Proportion of patients admitted to a hospital due to COVID-19 [ Time Frame: Through Day 29 ]
  • Proportion of patients admitted to an intensive care unit (ICU) due to COVID-19 [ Time Frame: Through Day 29 ]
  • Proportion of patients at least 1 outpatient or telemedicine visit due to COVID-19 [ Time Frame: Through Day 29 ]
  • Proportion of patients requiring mechanical ventilation due to COVID-19 [ Time Frame: Through Day 29 ]
  • Serum concentration of REGN10933 over time [ Time Frame: Through Day 29 ]
  • Serum concentration of REGN10987 over time [ Time Frame: Through Day 29 ]
  • Assessment of pharmacokinetic (PK) parameter: maximum serum concentration observed (Cmax) of REGN10933 [ Time Frame: Through Day 29 ]
    Phase 1 Only
  • Assessment of PK parameter: maximum serum concentration observed (Cmax) of REGN10987 [ Time Frame: Through Day 29 ]
    Phase 1 Only
  • Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) of REGN10933 [ Time Frame: Through Day 29 ]
    Phase 1 Only
  • Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) of REGN10987 [ Time Frame: Through Day 29 ]
    Phase 1 Only
  • Assessment of PK parameter: Time to Cmax (tmax) for REGN10933 [ Time Frame: Through Day 29 ]
    Phase 1 Only
  • Assessment of PK parameter: Time to Cmax (tmax) for REGN10987 [ Time Frame: Through Day 29 ]
    Phase 1 Only
  • Assessment of PK parameter: Area Under the Curve (AUC) computed from time zero to the time of the last positive concentration (AUClast) for REGN10933 [ Time Frame: Through Day 29 ]
    Phase 1 Only
  • Assessment of PK parameter: AUC computed from time zero to the time of the last positive concentration (AUClast) for REGN10987 [ Time Frame: Through Day 29 ]
    Phase 1 Only
  • Incidence of anti-drug antibodies (ADA) to REGN10933 [ Time Frame: Through Day 29 ]
  • Incidence of anti-drug antibodies (ADA) to REGN10987 [ Time Frame: Through day 29 ]
  • Number of days of hospitalization due to COVID-19 [ Time Frame: Through Day 29 ]
    Phase 2, Phase 3
  • Number of deaths due to any cause (All-Cause Mortality) [ Time Frame: Through Day 29 ]
    Phase 2, Phase 3
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Adult and Pediatric Patients With COVID-19
Official Title  ICMJE A Master Protocol Assessing the Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Patients With COVID-19
Brief Summary

Phase 1

  • To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo
  • To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral load of SARS-CoV-2

Phase 2

• To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral load of SARS-CoV-2

Phase 3

  • Cohort 1 (≥18 Years Old, Not Pregnant at Randomization)

    • To evaluate the clinical efficacy of REGN10933+REGN10987 compared to placebo as measured by COVID-19-related hospitalizations or all-cause death

  • Cohort 2 (<18 Years Old, Not Pregnant at Randomization)

    • To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo
    • To further characterize the concentrations of REGN10933 and REGN10987 in serum over time
  • Cohort 3 (Pregnant at Randomization) • To evaluate the safety and tolerability of REGN10933+REGN10987
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Phase 1/Phase 2/Phase 3
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE
  • Drug: REGN10933+REGN10987 combination therapy
    Administered intravenously (IV) single dose
    Other Names:
    • REGN-COV2
    • casirivimab
    • imdevimab
    • REGEN-COV™
  • Drug: Placebo
    Placebo IV Single Dose
Study Arms  ICMJE
  • Experimental: REGN10933+REGN10987 low dose
    Intervention: Drug: REGN10933+REGN10987 combination therapy
  • Experimental: REGN10933+REGN10987 high dose
    Intervention: Drug: REGN10933+REGN10987 combination therapy
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications * Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, Musser BJ, Soo Y, Rofail D, Im J, Perry C, Pan C, Hosain R, Mahmood A, Davis JD, Turner KC, Hooper AT, Hamilton JD, Baum A, Kyratsous CA, Kim Y, Cook A, Kampman W, Kohli A, Sachdeva Y, Graber X, Kowal B, DiCioccio T, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD; Trial Investigators. REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. N Engl J Med. 2021 Jan 21;384(3):238-251. doi: 10.1056/NEJMoa2035002. Epub 2020 Dec 17.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 11, 2020)
6420
Original Estimated Enrollment  ICMJE
 (submitted: June 8, 2020)
1054
Estimated Study Completion Date  ICMJE August 28, 2021
Estimated Primary Completion Date April 10, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Has SARS-CoV-2-positive diagnostic test (from a sample collected ≤72 hours prior to randomization, using a validated SARS-CoV-2 antigen, RT-PCR, or other molecular diagnostic assay, and an appropriate sample such as nasopharyngeal [NP], nasal, oropharyngeal [OP], or saliva)
  • Has symptoms consistent with COVID-19, as determined by the investigator, with onset ≤7 days before randomization
  • Maintains O2 saturation ≥93% on room air
  • Is able to understand and complete study-related questionnaires (patients aged ≥12 years only)

Key Exclusion Criteria:

  • Was admitted to a hospital for COVID-19 prior to randomization, or is hospitalized (inpatient) for any reason at randomization
  • Has participated, or is participating, in a clinical research study evaluating COVID-19 convalescent plasma, mAbs against SARS-CoV-2 (eg, bamlanivimab), 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 90 days of study drug administration or per current CDC recommendations, as applicable) of any authorized or approved vaccine for COVID-19
  • Has participated, is participating or plans to participate in a clinical research study evaluation any authorized, approved or investigational vaccine for COVID-19

NOTE: Other Protocol defined Inclusion/Exclusion criteria apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Trials Administrator 844-734-6643 clinicaltrials@regeneron.com
Listed Location Countries  ICMJE Chile,   Mexico,   Romania,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04425629
Other Study ID Numbers  ICMJE R10933-10987-COV-2067
2020-003690-21 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: Analytic Code
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
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., Food and Drug Administration (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).
URL: https://vivli.org/
Responsible Party Regeneron Pharmaceuticals
Study Sponsor  ICMJE Regeneron Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trial Management Regeneron Pharmaceuticals
PRS Account Regeneron Pharmaceuticals
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP