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

Study at a glance

From the registry record, last updated by the sponsor on 27 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

A Master Protocol Assessing the Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Hospitalized Patients With COVID-19

ClinicalTrials.gov ID

NCT04426695

Acronym / sponsor ID

R10933-10987-COV-2066

Conditions

COVID-19

Keywords

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

Phase

Phase 1/2

Study type

Interventional

Recruitment status

Completed

Enrolment

2,252 participants (actual)

Lead sponsor

Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)

Study start

10 Jun 2020 (actual)

Primary completion

7 May 2021 (actual)

Study completion

22 Oct 2021 (actual)

First posted

11 Jun 2020 (actual)

Results

Posted 25 Jul 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Randomised

Intervention model

Parallel groups

Masking

Quadruple blind (participant, care provider, investigator, outcomes assessor)

Number of arms

4

Model description

Phase 1/Phase 2/Phase 3

Who may qualify

Ages

18 years and older

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Time-weighted Average (TWA) Change in Viral Load in Nasopharyngeal (NP) Samples Based on Seronegative mFAS

   Time frame: Day 1 to Day 7

   Time-weighted average daily change from Day 1 to Day 7 in viral load (log10 copies/mL), as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples.

2. Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 6 Through Day 29 Based on High Viral Load mFAS

   Time frame: Day 6 to Day 29

   Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on high viral load mFAS were reported.

3. Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 6 Through Day 29 Based on Seronegative mFAS

   Time frame: Day 6 to Day 29

   Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on seronegative mFAS were reported.

4. Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 6 Through Day 29 Based on Overall mFAS

   Time frame: Day 6 to Day 29

   Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on overall FAS were reported.

5. Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 1 Through Day 29 Based on High Viral Load mFAS

   Time frame: Day 1 to Day 29

   Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on high viral load mFAS were reported.

6. Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 1 Through Day 29 Based on Seronegative mFAS

   Time frame: Day 1 to Day 29

   Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on seronegative mFAS were reported.

7. Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 1 Through Day 29 Based on Overall mFAS

   Time frame: Day 1 to Day 29

   Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on overall mFAS were reported.

8. Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Treatment-Emergent Serious Adverse Events

   Time frame: Up to Day 169

   Treatment-emergent adverse events are defined as those that are not present at baseline or represent the exacerbation of a pre-existing condition during the observation period.

9. Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Grade >=2 Infusion Related Reactions up to Day 4

   Time frame: Up to Day 4

   Infusion-related reactions are defined as any relevant adverse event that occurs during the infusion or up to day 4. The severity of adverse events (including test findings classified as adverse events) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).

10. Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Grade >=2 Hypersensitivity Reactions Up to Day 29

    Time frame: Up to Day 29

    Hypersensitivity reactions are defined as any relevant adverse event that occurs during the infusion or up to study day 29. The severity of adverse events (including test findings classified as adverse events) were graded according to NCI-CTCAE.

11. Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Cumulative Incidence of Death or Mechanical Ventilation Based on Seronegative mFAS

    Time frame: Up to Day 29

    Cumulative incidence percentage was estimated using Kaplan-Meier method.

12. Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Cumulative Incidence of Death or Mechanical Ventilation Based on High Viral Load mFAS

    Time frame: Up to Day 29

    Cumulative incidence percentage was estimated using Kaplan-Meier method.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2023.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 37229174Somersan-Karakaya S, Mylonakis E, Mou J, Oviedo-Orta E, O'Brien MP, Mas Casullo V, Mahmood A, Hooper AT, Hussein M, Ali S, Marty FM, Forleo-Neto E, Bhore R, Hamilton JD, Herman GA, Hirshberg B, Weinreich DM. Effectiveness of Casirivimab and Imdevimab Antibody Combination in Immunocompromised Hospitalized Patients With Coronavirus Disease 2019: A Post Hoc Analysis in a Phase 1/2/3 Double-Blind Trial. Open Forum Infect Dis. 2023 Apr 19;10(5):ofad211. doi: 10.1093/ofid/ofad211. eCollection 2023 May.
• Derived from this study: PubMed 36255239Hooper AT, Somersan-Karakaya S, McCarthy SE, Mylonakis E, Ali S, Mei J, Bhore R, Mahmood A, Geba GP, Dakin P, Weinreich DM, Yancopoulos GD, Herman GA, Hamilton JD; COVID-19 Phase 2/3 Hospitalized Trial Team. Casirivimab and Imdevimab Treatment Reduces Viral Load and Improves Clinical Outcomes in Seropositive Hospitalized COVID-19 Patients with Nonneutralizing or Borderline Neutralizing Antibodies. mBio. 2022 Dec 20;13(6):e0169922. doi: 10.1128/mbio.01699-22. Epub 2022 Oct 18.
• Derived from this study: PubMed 35895508Somersan-Karakaya S, Mylonakis E, Menon VP, Wells JC, Ali S, Sivapalasingam S, Sun Y, Bhore R, Mei J, Miller J, Cupelli L, Forleo-Neto E, Hooper AT, Hamilton JD, Pan C, Pham V, Zhao Y, Hosain R, Mahmood A, Davis JD, Turner KC, Kim Y, Cook A, Kowal B, Soo Y, DiCioccio AT, Geba GP, Stahl N, Lipsich L, Braunstein N, Herman GA, Yancopoulos GD, Weinreich DM; COVID-19 Phase 2/3 Hospitalized Trial Team. Casirivimab and Imdevimab for the Treatment of Hospitalized Patients With COVID-19. J Infect Dis. 2022 Dec 28;227(1):23-34. doi: 10.1093/infdis/jiac320.
• Derived from this study: PubMed 35713300Hirsch 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.
• Derived from this study: PubMed 34473343Kreuzberger 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.
• Individual participant dataSharing planned: Yes. All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

123 sites in 6 countries: see every site and its status.