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

Sponsor
Regeneron Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04425629
Collaborator
(none)
10,500
Enrollment
115
Locations
1
Arm
23
Anticipated Duration (Months)
91.3
Patients Per Site
4
Patients Per Site Per Month

Study Details

Study Description

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

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: casirivimab+imdevimab combination therapy
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
10500 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
Phase 1/Phase 2/Phase 3Phase 1/Phase 2/Phase 3
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Jun 16, 2020
Anticipated Primary Completion Date :
Dec 29, 2021
Anticipated Study Completion Date :
May 18, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: casirivimab+imdevimab low dose

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

Drug: casirivimab+imdevimab combination therapy
Administered intravenously (IV) single dose
Other Names:
  • REGN-COV2
  • REGN10933
  • REGN10987
  • REGEN-COV™
  • Ronapreve™
  • Outcome Measures

    Primary Outcome Measures

    1. Proportion of patients with treatment-emergent serious adverse events (SAEs) [Through Day 29]

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

    2. Proportion of patients with infusion-related reactions [Through Day 4]

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

    3. Proportion of patients with hypersensitivity reactions [Through Day 29]

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

    4. 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 [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)

    5. Proportion of patients with at least one (≥1) COVID-19-related hospitalization or all-cause death [Through Day 29]

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

    6. Concentration of REGN10933 in serum over time [Through Day 29]

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

    7. Concentration of REGN10987 in serum over time [Through Day 29]

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

    Secondary Outcome Measures

    1. Time-weighted average change from baseline in viral load (log10 copies/mL), as measured by RT-qPCR in saliva samples [Baseline up to Day 22]

      Phase 1 Only

    2. Time-weighted average change from baseline in viral load (log10 copies/mL), as measured by RT-qPCR in nasal swab samples [Baseline up to Day 22]

      Phase 1 Only

    3. Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR in any tested samples [Through Day 29]

      Phase 1 Only

    4. Time to negative RT-qPCR in nasopharyngeal swabs with no subsequent positive RT-qPCR [Through Day 29]

      Phase 2 Only

    5. Change from baseline in viral load at each visit, as measured by RT-qPCR in nasopharyngeal swabs [Baseline up to Day 29]

      Phase 1, Phase 2, Phase 3 (Cohort 1 and Cohort 2)

    6. Change from baseline in viral load at each visit, as measured by RT-qPCR in saliva samples [Baseline up to Day 29]

      Phase 1 Only

    7. Change from baseline in viral load at each visit, as measured by RT-qPCR in nasal swabs [Baseline up to Day 29]

      Phase 1 Only

    8. Correlation of RT-qPCR results over time between different sample types (NP, nasal, and saliva) [Up to Day 29]

      Phase 1 Only

    9. Concordance of RT-qPCR results over time between different sample types (NP, nasal, and saliva) [Up to Day 29]

      Phase 1 Only

    10. Time-weighted average change from baseline in viral load (log10 copies/mL) from day 1 to post-baseline study days [Day 1 to Day 29]

      Phase 1, Phase 2

    11. Proportion of participants with ≥1 COVID-19-related medically-attended visit [Through Day 29]

      Phase 1, Phase 2

    12. Proportion of participants with ≥2 COVID-19-related medically-attended visit [Through Day 29]

      Phase 1, Phase 2, Phase 3 (Cohort 1 and Cohort 2)

    13. Total number of COVID-19-related medically-attended visits [Through Day 29]

      Phase 1, Phase 2, Phase 3 (Cohort 1 and Cohort 2)

    14. Proportion of participants admitted to a hospital due to COVID-19 [Through Day 29]

      Phase 1, Phase 2

    15. Proportion of participants with ≥1 outpatient or telemedicine visit due to COVID-19 [Through Day 29]

      Phase 1, Phase 2

    16. Assessment of pharmacokinetic (PK) parameter: maximum serum concentration observed (Cmax) of REGN10933 [Through Day 29]

      Phase 1 Only

    17. Assessment of PK parameter: maximum serum concentration observed (Cmax) of REGN10987 [Through Day 29]

      Phase 1 Only

    18. Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) of REGN10933 [Through Day 29]

      Phase 1 Only

    19. Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) of REGN10987 [Through Day 29]

      Phase 1 Only

    20. Assessment of PK parameter: Time to Cmax (tmax) for REGN10933 [Through Day 29]

      Phase 1 Only

    21. Assessment of PK parameter: Time to Cmax (tmax) for REGN10987 [Through Day 29]

      Phase 1 Only

    22. Assessment of PK parameter: Area Under the Curve (AUC) computed from time zero to the time of the last positive concentration (AUClast) for REGN10933 [Through Day 29]

      Phase 1 Only

    23. Assessment of PK parameter: AUC computed from time zero to the time of the last positive concentration (AUClast) for REGN10987 [Through Day 29]

      Phase 1 Only

    24. Immunogenicity as measured by anti-drug (ADA) to REGN10933 [Through Day 29]

      Phase 1, Phase 2, Phase 3 (Cohort 1, Cohort 2 and Cohort 3)

    25. Immunogenicity as measured by ADA to REGN10987 [Through Day 29]

      Phase 1, Phase 2, Phase 3 (Cohort 1, Cohort 2 and Cohort 3)

    26. Immunogenicity as measured by neutralizing antibodies (NAbs) to REGN10933 [Through Day 29]

      Phase 2, Phase 3 (Cohort 1, Cohort 2 and Cohort 3)

    27. Immunogenicity as measured by NAbs to REGN10987 [Through Day 29]

      Phase 2, Phase 3 (Cohort 1, Cohort 2 and Cohort 3)

    28. Proportion of participants with high viral load at each visit [Through Day 29]

      Phase 2 Only

    29. Proportion of participants with viral loads below the limit of detection at each visit [Through Day 29]

      Phase 2 Only

    30. Proportion of participants with viral loads below the lower limit of quantitation at each visit [Through Day 29]

      Phase 2 Only

    31. Proportion of participants admitted to an intensive care unit (ICU) due to COVID-19 [Through Day 29]

      Phase 2, Phase 3 (Cohort 1 and Cohort 2)

    32. Proportion of participants requiring mechanical ventilation due to COVID-19 [Through Day 29]

      Phase 2, Phase 3 (Cohort 1 and Cohort 2)

    33. Number of days of hospitalization due to COVID-19 [Through Day 29]

      Phase 2, Phase 3 (Cohort 1 and Cohort 2)

    34. Proportion of participants with all-cause mortality [Through Day 29]

      Phase 2 Only

    35. Time to first onset of symptoms consistent with COVID-19 (asymptomatic cohort only) [Up to Day 29]

      Phase 2 Only

    36. Duration of symptoms consistent with COVID-19 [Up to Day 29]

      Phase 2 Only

    37. Proportion of participants with ≥1 COVID-19-related hospitalization or all-cause death [From Day 4 Through Day 29]

      Phase 3 (Cohort 1 and Cohort 2)

    38. Time to COVID-19 symptoms resolution [Through Day 29]

      Phase 3 (Cohort 1)

    39. Proportion of participants with ≥1 COVID-19-related hospitalization, emergency room visit, or all-cause death [Through day 29]

      Phase 3 (Cohort 1 and Cohort 2)

    40. Proportion of patients with (≥1) COVID-19-related medically-attended visit or all-cause death [Through Day 29]

      Phase 3 (Cohort 1 and Cohort 2)

    41. Proportion of participants with ≥1 COVID-19-related medically-attended visit by type of visit [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

    42. Cumulative incidence of patients with ≥1 COVID-19-related hospitalization or all-cause death [Through Day 29]

      Phase 3 (Cohort 1 and Cohort 2)

    43. Cumulative incidence of patients with ≥1 COVID-19-related hospitalization, emergency room visit, or all-cause death [Through Day 29]

      Phase 3 (Cohort 1 and Cohort 2)

    44. Cumulative incidence of patients with ≥1 COVID-19-related medically-attended visit or all-cause death [Through Day 29]

      Phase 3 (Cohort 1 and Cohort 2)

    45. Proportion of participants requiring supplemental oxygen due to COVID-19 [Through Day 29]

      Phase 3 (Cohort 1 and Cohort 2)

    46. Time to all-cause death [Through Day 169]

      Phase 3 (Cohort 1 and Cohort 2)

    47. All-cause death [By Day 29, Day 120, and Day 169]

      Phase 3 (Cohort 1 and Cohort 2)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Regeneron Study SiteMesaArizonaUnited States85210
    2Regeneron Study SiteTucsonArizonaUnited States85712
    3Regeneron Study SiteTucsonArizonaUnited States85724
    4Regeneron Study SiteCanoga ParkCaliforniaUnited States91303
    5Regeneron Study SiteLa MesaCaliforniaUnited States91942
    6Regeneron Study SiteLa PalmaCaliforniaUnited States90623
    7Regeneron Study Site 1Long BeachCaliforniaUnited States90806
    8Regeneron Study Site 2Long BeachCaliforniaUnited States90806
    9Regeneron Study Site 3Long BeachCaliforniaUnited States90806
    10Regeneron Study SiteLos AngelesCaliforniaUnited States90036
    11Regeneron Study SiteMontclairCaliforniaUnited States91763
    12Regeneron Study SiteRolling Hills EstatesCaliforniaUnited States90274
    13Regeneron Study SiteSacramentoCaliforniaUnited States95817
    14Regeneron Study SiteSan FranciscoCaliforniaUnited States94127
    15Regeneron Study SiteSanta MonicaCaliforniaUnited States90404
    16Regeneron Study SiteStanfordCaliforniaUnited States94305
    17Regeneron Study SiteAuroraColoradoUnited States80045
    18Regeneron Study SiteColorado SpringsColoradoUnited States80907
    19Regeneron Study SiteWashingtonDistrict of ColumbiaUnited States20037
    20Regeneron Study SiteBoca RatonFloridaUnited States33487
    21Regeneron Study SiteDeLandFloridaUnited States32720
    22Regeneron Study SiteFort PierceFloridaUnited States34982
    23Regeneron Study SiteHialeahFloridaUnited States33010
    24Regeneron Study SiteLoxahatchee GrovesFloridaUnited States33470
    25Regeneron Study SiteMaitlandFloridaUnited States32751
    26Regeneron Study SiteMiamiFloridaUnited States33012
    27Regeneron Study Site 1MiamiFloridaUnited States33126
    28Regeneron Study Site 2MiamiFloridaUnited States33126
    29Regeneron Study SiteMiamiFloridaUnited States33130
    30Regeneron Study SiteMiamiFloridaUnited States33144
    31Regeneron Study SiteMiamiFloridaUnited States33184
    32Regeneron Study SiteSaint PetersburgFloridaUnited States33705
    33Regeneron Study SiteSarasotaFloridaUnited States34239
    34Regeneron Study SiteTampaFloridaUnited States33606
    35Regeneron Study SiteWest Palm BeachFloridaUnited States33407
    36Regeneron Study SiteWinter HavenFloridaUnited States33880
    37Regeneron Study SiteWinter ParkFloridaUnited States32789
    38Regeneron Study SiteAtlantaGeorgiaUnited States30309
    39Regeneron Study SiteAtlantaGeorgiaUnited States30322
    40Regeneron Study SiteAugustaGeorgiaUnited States30912
    41Regeneron Study SiteColumbusGeorgiaUnited States31904
    42Regeneron Study SiteMariettaGeorgiaUnited States30060
    43Regeneron Study SiteChicagoIllinoisUnited States60607
    44Regeneron Study Site 1Downers GroveIllinoisUnited States60515
    45Regeneron Study Site 2Downers GroveIllinoisUnited States60515
    46Regeneron Study SiteDowners GroveIllinoisUnited States60515
    47Regeneron Study SiteAmesIowaUnited States50010-3014
    48Regeneron Study SiteIowa CityIowaUnited States52242
    49Regeneron Study SiteLake CharlesLouisianaUnited States70601
    50Regeneron Study SiteMarreroLouisianaUnited States70072
    51Regeneron Study SiteNew OrleansLouisianaUnited States70114
    52Regeneron Study SiteShreveportLouisianaUnited States71118
    53Regeneron Study SiteBaltimoreMarylandUnited States21201
    54Regeneron Study SiteRoyal OakMichiganUnited States48073
    55Regeneron Study SiteJacksonMississippiUnited States39216
    56Regeneron Study SiteLas VegasNevadaUnited States89109
    57Regeneron Study SiteRidgewoodNew JerseyUnited States07450
    58Regeneron Study SiteTeaneckNew JerseyUnited States07666
    59Regeneron Study SiteSanta FeNew MexicoUnited States87505
    60Regeneron Study SiteBronxNew YorkUnited States10451
    61Regeneron Study SiteBronxNew YorkUnited States10461
    62Regeneron Study SiteJamaicaNew YorkUnited States11432
    63Regeneron Study SiteNew YorkNew YorkUnited States10003
    64Regeneron Study SiteNew YorkNew YorkUnited States10019
    65Regeneron Study SiteNew YorkNew YorkUnited States10025
    66Regeneron Study SiteNew YorkNew YorkUnited States10029
    67Regeneron Study SiteNew YorkNew YorkUnited States10032
    68Regeneron Study SiteNew YorkNew YorkUnited States10037
    69Regeneron Study SiteCharlotteNorth CarolinaUnited States28209
    70Regeneron Study SiteDurhamNorth CarolinaUnited States27710
    71Regeneron Study SiteWilmingtonNorth CarolinaUnited States28401
    72Regeneron Study SiteColumbusOhioUnited States43215
    73Regeneron Study SiteDaytonOhioUnited States45409
    74Regeneron Study SiteDaytonOhioUnited States45432
    75Regeneron Study SitePhiladelphiaPennsylvaniaUnited States19140
    76Regeneron Study SiteProvidenceRhode IslandUnited States02903
    77Regeneron Study SiteCharlestonSouth CarolinaUnited States29425
    78Regeneron Study SiteClintonSouth CarolinaUnited States29325
    79Regeneron Study SiteSioux FallsSouth DakotaUnited States57108
    80Regeneron Study Site 2MemphisTennesseeUnited States38103
    81Regeneron Study SiteMemphisTennesseeUnited States38103
    82Regeneron Study SiteAmarilloTexasUnited States79109
    83Regeneron Study SiteCorpus ChristiTexasUnited States78413
    84Regeneron Study SiteDallasTexasUnited States75246
    85Regeneron Study SiteDallasTexasUnited States75390
    86Regeneron Study SiteHoustonTexasUnited States77004
    87Regeneron Study SiteHoustonTexasUnited States77008
    88Regeneron Study SiteHoustonTexasUnited States77030
    89Regeneron Study SiteHoustonTexasUnited States77055
    90Regeneron Study SiteHoustonTexasUnited States77057
    91Regeneron Study SiteHoustonTexasUnited States77093
    92Regeneron Study SitePearlandTexasUnited States77584
    93Regeneron Study SiteRed OakTexasUnited States75154
    94Regeneron Study SiteSan AntonioTexasUnited States78215
    95Regeneron Study SiteSan AntonioTexasUnited States78217
    96Regeneron Study SiteSan AntonioTexasUnited States78249
    97Regeneron Study SiteTylerTexasUnited States75708
    98Regeneron Study SiteFalls ChurchVirginiaUnited States22042
    99Regeneron Study SiteEverettWashingtonUnited States98201
    100Regeneron Study SiteSeattleWashingtonUnited States98109
    101Regeneron Study SiteSeattleWashingtonUnited States98122
    102Regeneron Study SiteMadisonWisconsinUnited States53792
    103Regeneron Study SiteLas CondesSantiago De ChileChile7591047
    104Regeneron Study SiteGuadalajaraJaliscoMexico44280
    105Regeneron Study SiteGuadalajaraJaliscoMexico44340
    106Regeneron Study SiteZapopanJaliscoMexico45070
    107Regeneron Study SiteMonterreyNuevo LeonMexico64718
    108Regeneron Study SiteMonterreyNuevo LeónMexico64710
    109Regeneron Study SiteMeridaYucatanMexico97070
    110Regeneron Study SiteChihuahuaMexico31238
    111Regeneron Study SiteCiudad de MexicoMexico3100
    112Regeneron Study SiteDurangoMexico34000
    113Regeneron Study SiteMéridaMexico97000
    114Regeneron Study SiteVeracruzMexico91900
    115Regeneron Study SiteBucurestiRomania021105

    Sponsors and Collaborators

    • Regeneron Pharmaceuticals

    Investigators

    • Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Regeneron Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT04425629
    Other Study ID Numbers:
    • R10933-10987-COV-2067
    • 2020-003690-21
    First Posted:
    Jun 11, 2020
    Last Update Posted:
    Oct 8, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Regeneron Pharmaceuticals
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 8, 2021