Clinical trial NCT04666441: COVID-19 Study Assessing the Virologic Efficacy of REGN10933+REGN10987 Across Different Dose Regimens in Adult Outpatients With SARS-CoV-2 Infection
Official title: A Phase 2 Study to Assess the Virologic Efficacy of REGN10933+REGN10987 Across Different Dose Regimens in Outpatients With SARS-CoV-2 Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Keywords: Coronavirus disease 2019 (COVID-19)
Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) coronavirus
Non-hospitalized
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-12-14
Enrollment: 1149
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: Time-Weighted Average Daily Change From Day 1 in Viral Load in NP Swab Samples
timeFrame: Day 1 to Day 7
Secondary outcomes:
measure: Time-Weighted Average Daily Change From Day 1 in Viral Load
timeFrame: Day 1 to Day 5
measure: Time-Weighted Average Daily Change From Day 1 in Viral Load in Participants With High Viral Load at Baseline
timeFrame: Day 1 to Day 7
measure: Time-Weighted Average Daily Change From Day 1 in Viral Load in Participants With High Viral Load at Baseline
timeFrame: Day 1 to Day 5
measure: Number of Participants With High Viral Load
timeFrame: Day 1, Day 3, Day 5, Day 7, Day 15, Day 22
measure: Number of Participants With Viral Loads Below the Limit of Detection
timeFrame: Day 1, Day 3, Day 5, Day 7, Day 15, Day 22
measure: Number of Participants With Viral Loads Below the Lower Limit of Quantification
timeFrame: Day 1, Day 3, Day 5, Day 7, Day 15, Day 22
measure: Change From Day 1 in Viral Load as Measured by RT-qPCR in NP Swab Samples
timeFrame: Day 3, Day 5, Day 7, Day 15, Day 22
measure: Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
timeFrame: Through day 29
measure: Number of Participants With Infusion-Related Reactions Grade 2 or Above
timeFrame: Through day 4
measure: Number of Participants With Injection-Site Reactions Grade 3 or Above
timeFrame: Through day 4
measure: Number of Participants With Hypersensitivity Reactions Grade 2 or Above
timeFrame: Through day 29
measure: Concentration of REGN10933 in Serum
timeFrame: Pre-Dose, 15 minutes Post-Dose, 3 days Post-Dose, 5 days Post-Dose, 7 days Post-Dose, 120 days Post-Dose
measure: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10933
timeFrame: Through day 120
measure: Immunogenicity as Measured by Neutralizing Anti-drug Antibody (NAb) to REGN10933
timeFrame: Through day 120
measure: Concentration of REGN10987 in Serum
timeFrame: Pre-Dose, 15 minutes Post-Dose, 3 days Post-Dose, 5 days Post-Dose, 7 days Post-Dose, 120 days Post-Dose
measure: Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10987
timeFrame: Through day 120
measure: Immunogenicity as Measured by Neutralizing Anti-drug Antibody (NAb) to REGN10987
timeFrame: Through day 120
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Regeneron Study Site
state: Arizona
city: Tucson
country: United States
facility: Regeneron Study Site
state: Arizona
city: Canoga Park
country: United States
facility: Regeneron Study Site
state: California
city: Long Beach
country: United States
facility: Regeneron Study Site
state: California
city: Los Angeles
country: United States
facility: Regeneron Study Site
state: California
city: Rolling Hills Estates
country: United States
facility: Regeneron Study Site
state: California
city: San Francisco
country: United States
facility: Regeneron Study Site
state: California
city: Santa Monica
country: United States
facility: Regeneron Study Site
state: California
city: Stanford
country: United States
facility: Regeneron Study Site
state: California
city: Colorado Springs
country: United States
facility: Regeneron Study Site
state: Colorado
city: Washington
country: United States
facility: Regeneron Study Site
state: District of Columbia
city: DeLand
country: United States
facility: Regeneron Study Site
state: Florida
city: Fort Pierce
country: United States
facility: Regeneron Study Site
state: Florida
city: Hialeah
country: United States
facility: Regeneron Study Site
state: Florida
city: Hialeah
country: United States
facility: Regeneron Study Site
state: Florida
city: Maitland
country: United States
facility: Regeneron Study Site
state: Florida
city: Miami
country: United States
facility: Regeneron Study Site
state: Florida
city: Miami
country: United States
facility: Regeneron Study Site
state: Florida
city: Saint Petersburg
country: United States
facility: Regeneron Study Site
state: Florida
city: Tampa
country: United States
facility: Regeneron Study Site
state: Florida
city: West Palm Beach
country: United States
facility: Regeneron Study Site
state: Florida
city: Winter Haven
country: United States
facility: Regeneron Study Site
state: Florida
city: Winter Park
country: United States
facility: Regeneron Study Site
state: Florida
city: Atlanta
country: United States
facility: Regeneron Study Site
state: Georgia
city: Columbus
country: United States
facility: Regeneron Study Site
state: Georgia
city: Downers Grove
country: United States
facility: Regeneron Study Site
state: Illinois
city: Ames
country: United States
facility: Regeneron Study Site
state: Iowa
city: Iowa City
country: United States
facility: Regeneron Study Site
state: Iowa
city: Lake Charles
country: United States
facility: Regeneron Study Site
state: Louisiana
city: Marrero
country: United States
facility: Regeneron Study Site
state: Louisiana
city: Shreveport
country: United States
facility: Regeneron Study Site
state: Louisiana
city: Baltimore
country: United States
facility: Regeneron Study Site
state: Maryland
city: Las Vegas
country: United States
facility: Regeneron Study Site
state: Nevada
city: Teaneck
country: United States
facility: Regeneron Study Site
state: New Jersey
city: Bronx
country: United States
facility: Regeneron Study Site
state: New York
city: New York
country: United States
facility: Regeneron Study Site
state: New York
city: Charlotte
country: United States
facility: Regeneron Study Site
state: North Carolina
city: Durham
country: United States
facility: Regeneron Study Site
state: North Carolina
city: Wilmington
country: United States
facility: Regeneron Study Site
state: North Carolina
city: Columbus
country: United States
facility: Regeneron Study Site
state: Ohio
city: Dayton
country: United States
facility: Regeneron Study Site
state: Ohio
city: Dayton
country: United States
facility: Regeneron Study Site
state: Ohio
city: Philadelphia
country: United States
facility: Regeneron Study Site
state: Pennsylvania
city: Charleston
country: United States
facility: Regeneron Study Site
state: South Carolina
city: Clinton
country: United States
facility: Regeneron Study Site
state: South Carolina
city: Amarillo
country: United States
facility: Regeneron Study Site
state: Texas
city: Corpus Christi
country: United States
facility: Regeneron Study Site
state: Texas
city: Houston
country: United States
facility: Regeneron Study Site
state: Texas
city: Houston
country: United States
facility: Regeneron Study Site
state: Texas
city: Houston
country: United States
facility: Regeneron Study Site
state: Texas
city: Houston
country: United States
facility: Regeneron Study Site
state: Texas
city: Pearland
country: United States
facility: Regeneron Study Site
state: Texas
city: Red Oak
country: United States
facility: Regeneron Study Site
state: Texas
city: San Antonio
country: United States
facility: Regeneron Study Site
state: Texas
city: Splendora
country: United States
facility: Regeneron Study Site
state: Texas
city: Tyler
country: United States
facility: Regeneron Study Site
state: Texas
city: Falls Church
country: United States
facility: Regeneron Study Site
state: Virginia
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.