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

NCT04425629 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: R10933-10987-COV-20672020-003690-21
• Study Type: interventional
• Target: 10,078
• Locations: 3 countries
• Sites: 114

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

Conditions

COVID-19

Keywords

Coronavirus disease 2019 (COVID-19); Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2); coronavirus

Outcome Measures

Primary Outcomes (7)

• Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3]

  Primary: Phase 1, Phase 3 (Cohort 2 and Cohort 3) Secondary: Phase 2, Phase 3 (Cohort 1)

  Through Day 29

• Number of Participants With Infusion-related Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3)

  Primary: Phase 1, Phase 3 (Cohort 2 and Cohort 3) Secondary: Phase 2, Phase 3 (Cohort 1)

  Through Day 4

• Number of Participants With Hypersensitivity Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3)

  Primary: Phase 1, Phase 3 (Cohort 2 and Cohort 3) Secondary: Phase 2, Phase 3 (Cohort 1)

  Through Day 29

• Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Day 7, as Measured by Quantitative Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) in Nasopharyngeal (NP) Swab Samples (Ph1, Ph2)

  Primary: Phase 1, Phase 2

  Baseline up to Day 7

• Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death (Ph3 Cohort 1- 1.2g vs Placebo)

  Phase 3 Cohort 1

  Through Day 29

• Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death (Ph3 Cohort 1 - 2.4g vs Placebo)

  Primary: Phase 3 (Cohort 1)

  Through Day 29

• Concentration of REGN10983 + REGN10987 in Serum Over Time (Ph3 Cohort 2)

  Phase 3 Cohort 2 \[Nominal Sampling Time\] = \[Clinical Study Time (Visit Day - 1)\]

  Up to Nominal Sampling Day 28

Secondary Outcomes (84)

• Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 1.2g vs Placebo)

  Up to Day 29

• Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 2.4g vs Placebo)

  Through Day 29

• Proportion of Participants With ≥1 COVID-19-related Hospitalization or All-cause Death From Day 4 Through Day 29 (Ph3 Cohort 1 - 1.2g vs. Placebo)

  Day 4 thru Day 29

• Proportion of Participants With ≥1 COVID-19-related Hospitalization or All-cause Death From Day 4 Through Day 29 (Ph3 Cohort 1 - 2.4g vs. Placebo)

  From Day 4 Through Day 29

• Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs (Next Phase 2 Cohort)

  Day 5, Day 7, Day 15, Day 29

Study Arms (1)

casirivimab+imdevimab low dose

EXPERIMENTAL

Low dose or body-weight equivalent for those under 18 years of age.

Drug: casirivimab+imdevimab combination therapy

Interventions

casirivimab+imdevimab combination therapy DRUG

Administered intravenously (IV) single dose

Also known as: REGN-COV2, REGN10933, REGN10987, REGEN-COV™, Ronapreve™

casirivimab+imdevimab low dose

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (114)

Regeneron Study Site

Mesa, Arizona, 85210, United States

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Tucson, Arizona, 85712, United States

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Tucson, Arizona, 85724, United States

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Canoga Park, California, 91303, United States

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La Mesa, California, 91942, United States

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La Palma, California, 90623, United States

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Regeneron Study Site 1

Long Beach, California, 90806, United States

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Regeneron Study Site 2

Long Beach, California, 90806, United States

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Regeneron Study Site 3

Long Beach, California, 90806, United States

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Los Angeles, California, 90036, United States

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Montclair, California, 91763, United States

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Rolling Hills Estates, California, 90274, United States

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Sacramento, California, 95817, United States

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San Francisco, California, 94127, United States

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Santa Monica, California, 90404, United States

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Stanford, California, 94305, United States

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Aurora, Colorado, 80045, United States

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Colorado Springs, Colorado, 80907, United States

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Washington D.C., District of Columbia, 20037, United States

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Boca Raton, Florida, 33487, United States

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DeLand, Florida, 32720, United States

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Ft. Pierce, Florida, 34982, United States

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Hialeah, Florida, 33010, United States

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Loxahatchee Groves, Florida, 33470, United States

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Maitland, Florida, 32751, United States

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Miami, Florida, 33012, United States

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Regeneron Study Site 1

Miami, Florida, 33126, United States

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Regeneron Study Site 2

Miami, Florida, 33126, United States

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Miami, Florida, 33130, United States

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Miami, Florida, 33144, United States

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Miami, Florida, 33184, United States

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Sarasota, Florida, 34239, United States

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St. Petersburg, Florida, 33705, United States

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Tampa, Florida, 33606, United States

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West Palm Beach, Florida, 33407, United States

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Winter Haven, Florida, 33880, United States

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Winter Park, Florida, 32789, United States

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Atlanta, Georgia, 30309, United States

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Atlanta, Georgia, 30322, United States

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Augusta, Georgia, 30912, United States

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Columbus, Georgia, 31904, United States

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Marietta, Georgia, 30060, United States

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Chicago, Illinois, 60607, United States

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Downers Grove, Illinois, 60515, United States

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Regeneron Study Site 2

Downers Grove, Illinois, 60515, United States

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Downers Grove, Illinois, 60515, United States

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Ames, Iowa, 50010-3014, United States

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Iowa City, Iowa, 52242, United States

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Lake Charles, Louisiana, 70601, United States

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Marrero, Louisiana, 70072, United States

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New Orleans, Louisiana, 70114, United States

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Shreveport, Louisiana, 71118, United States

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Baltimore, Maryland, 21201, United States

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Royal Oak, Michigan, 48073, United States

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Jackson, Mississippi, 39216, United States

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Las Vegas, Nevada, 89109, United States

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Ridgewood, New Jersey, 07450, United States

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Teaneck, New Jersey, 07666, United States

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Santa Fe, New Mexico, 87505, United States

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Jamaica, New York, 11432, United States

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New York, New York, 10003, United States

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New York, New York, 10019, United States

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New York, New York, 10025, United States

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New York, New York, 10029, United States

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New York, New York, 10032, United States

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New York, New York, 10037, United States

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The Bronx, New York, 10451, United States

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The Bronx, New York, 10461, United States

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Charlotte, North Carolina, 28209, United States

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Durham, North Carolina, 27710, United States

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Wilmington, North Carolina, 28401, United States

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Columbus, Ohio, 43215, United States

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Dayton, Ohio, 45409, United States

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Dayton, Ohio, 45432, United States

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Philadelphia, Pennsylvania, 19140, United States

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Providence, Rhode Island, 02903, United States

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Charleston, South Carolina, 29425, United States

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Clinton, South Carolina, 29325, United States

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Sioux Falls, South Dakota, 57108, United States

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Regeneron Study Site 2

Memphis, Tennessee, 38103, United States

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Memphis, Tennessee, 38103, United States

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Amarillo, Texas, 79109, United States

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Corpus Christi, Texas, 78413, United States

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Dallas, Texas, 75246, United States

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Dallas, Texas, 75390, United States

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Houston, Texas, 77004, United States

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Houston, Texas, 77008, United States

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Houston, Texas, 77030, United States

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Houston, Texas, 77055, United States

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Houston, Texas, 77057, United States

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Houston, Texas, 77093, United States

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Pearland, Texas, 77584, United States

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Red Oak, Texas, 75154, United States

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San Antonio, Texas, 78215, United States

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San Antonio, Texas, 78217, United States

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San Antonio, Texas, 78249, United States

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Tyler, Texas, 75708, United States

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Falls Church, Virginia, 22042, United States

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Everett, Washington, 98201, United States

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Seattle, Washington, 98109, United States

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Seattle, Washington, 98122, United States

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Madison, Wisconsin, 53792, United States

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Guadalajara, Jalisco, 44280, Mexico

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Guadalajara, Jalisco, 44340, Mexico

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Zapopan, Jalisco, 45070, Mexico

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Monterrey, Nuevo León, 64710, Mexico

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Monterrey, Nuevo León, 64718, Mexico

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Mérida, Yucatán, 97070, Mexico

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Chihuahua City, 31238, Mexico

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Durango, 34000, Mexico

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Mexico City, 3100, Mexico

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Mérida, 97000, Mexico

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Veracruz, 91900, Mexico

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Bucharest, 021105, Romania

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Related Publications (7)

• Norton TD, Thakur M, Ganguly S, Ali S, Chao J, Waldron A, Xiao J, Patel Y, Turner KC, Davis JD, Irvin SC, Pan C, Atmodjo-Watkins D, Hooper AT, Hamilton JD, Subramaniam D, Bocchini JA, Kowal B, DiCioccio AT, Bhore R, Geba GP, Cox E, Braunstein N, Dakin P, Herman GA. Assessing the safety and pharmacokinetics of casirivimab and imdevimab (CAS+IMD) in a cohort of pregnant outpatients with COVID-19: results from an adaptive, multicentre, randomised, double-blind, phase 1/2/3 study. BMJ Open. 2024 Oct 8;14(10):e087431. doi: 10.1136/bmjopen-2024-087431.

  PMID: 39384241 DERIVED

• Rofail D, Hussein M, Naumann U, Podolanczuk AJ, Norton T, Ali S, Mastey V, Ivanescu C, Hirshberg B, Geba GP. Patient-Reported Outcomes in COVID-19 Treatment with Monoclonal Antibodies Reveal Benefits in Return to Usual Activities. Infect Dis Ther. 2024 Aug;13(8):1861-1876. doi: 10.1007/s40121-024-01013-1. Epub 2024 Jul 3.

  PMID: 38961047 DERIVED

• Bermejo-Gomez A, Aguilera-Alonso D, Rincon-Lopez EM, Catalan-Alonso P, Bardon-Cancho EJ, Garcia-Morin M, Manrique-Rodriguez S, Navarro-Gomez ML. Use of Monoclonal Antibodies in a Pediatric Patient With Severe Combined Immunodeficiency and Persistent SARS-CoV-2 Infection. Pediatr Infect Dis J. 2023 Aug 1;42(8):e290-e292. doi: 10.1097/INF.0000000000003938. Epub 2023 Apr 27.

  PMID: 37079569 DERIVED

• 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.

  PMID: 35713300 DERIVED

• Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, Xiao J, Hooper AT, Hamilton JD, Musser BJ, Rofail D, Hussein M, Im J, Atmodjo DY, Perry C, Pan C, Mahmood A, Hosain R, Davis JD, Turner KC, Baum A, Kyratsous CA, Kim Y, Cook A, Kampman W, Roque-Guerrero L, Acloque G, Aazami H, Cannon K, Simon-Campos JA, Bocchini JA, Kowal B, DiCioccio AT, Soo Y, Geba GP, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD; Trial Investigators. REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19. N Engl J Med. 2021 Dec 2;385(23):e81. doi: 10.1056/NEJMoa2108163. Epub 2021 Sep 29.

  PMID: 34587383 DERIVED

• 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.

  PMID: 34473343 DERIVED

• 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.

  PMID: 33332778 DERIVED

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

casirivimab and imdevimab drug combination; casirivimab; imdevimab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Nasal and saliva sample collection was discontinued early in the study because nasopharyngeal samples were determined to be more reliable for quantitative analysis, as such endpoints related to nasal or saliva samples were not analyzed. The Phase 1/2 SAP does not specify any analyses related to nasal and saliva samples collections

Results Point of Contact

• Title: Clinical Trials Administrator
• Organization: Regeneron Pharmaceuticals, Inc.

clinicaltrials@regeneron.com

8447346643

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: Phase 1/Phase 2/Phase 3

Study Record Dates

• First Submitted: June 8, 2020
• First Posted: June 11, 2020
• Study Start: June 16, 2020
• Primary Completion: January 21, 2022
• Study Completion: June 9, 2022
• Last Updated: December 21, 2023
• Results First Posted: December 21, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, 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).

Locations

ME (11); RO (1); US (102)