Phase 2
Completed N=2,252
Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for Hospitalized Adult Patients With COVID-19
Source: ClinicalTrials.gov NCT04426695 ↗Enrolled (actual)
2,252
Serious AEs
25.5%
Results posted
Jul 2022
Primary outcomePrimary: 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 — -1.03; -1.28; -1.34; -1.31 log10 copies/milliliter (mL) — p=0.0663
Summary
The primary objectives are:
Pooled Phase 3 (Cohort 1) and Phase 2 (Cohort 1A)
* To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral load of SARS-CoV-2
* To evaluate the clinical efficacy of REGN10933+REGN10987 compared to placebo, as measured by death or mechanical ventilation
Phase 1/2 (Cohort 1)
* To exclude futility of REGN10933+REGN10987 compared to placebo, as measured by death or mechanical ventilation
* To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
-1.03; -1.28; -1.34; -1.31 | 0.0663 |
| PRIMARY 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 |
13.3; 7.3; 12.4; 9.9 | 0.0431 sig |
| PRIMARY 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 |
15.0; 4.9; 10.6; 7.9 | 0.0039 sig |
| PRIMARY 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 |
10.6; 5.4; 10.7; 8.1 | 0.0085 sig |
| PRIMARY 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 |
18.8; 10.0; 14.4; 12.2 | 0.0092 sig |
| PRIMARY 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 |
19.4; 8.1; 12.2; 10.3 | 0.0045 sig |
| PRIMARY 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 |
14.8; 7.9; 12.6; 10.2 | 0.0023 sig |
| PRIMARY Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Treatment-Emergent Serious Adverse Events |
54; 45; 47; 92 | — |
| PRIMARY Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Grade >=2 Infusion Related Reactions up to Day 4 |
3; 2; 6; 8 | — |
| PRIMARY Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Grade >=2 Hypersensitivity Reactions Up to Day 29 |
1; 2; 2; 4 | — |
| PRIMARY Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Cumulative Incidence of Death or Mechanical Ventilation Based on Seronegative mFAS |
23.0; 15.1; 20.3; 17.6 | — |
| PRIMARY Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Cumulative Incidence of Death or Mechanical Ventilation Based on High Viral Load mFAS |
20.7; 18.9; 11.6; 15.3 | — |
| SECONDARY Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on High Viral Load mFAS |
11.4; 6.1; 8.5; 7.3 | 0.0575 |
| SECONDARY Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on Seronegative mFAS |
10.0; 5.8; 7.4; 6.7 | 0.2167 |
| SECONDARY Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 Through Day 29 Based on High Viral Load mFAS |
13.1; 7.1; 10.1; 8.6 | 0.0383 sig |
| SECONDARY Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 Through Day 29 Based on Seronegative mFAS |
13.7; 4.8; 7.2; 6.0 | 0.0070 sig |
| SECONDARY Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 Through Day 29 Based on High Viral Load mFAS |
14.4; 7.4; 11.0; 9.2 | 0.0174 sig |
| SECONDARY Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 Through Day 29 Based on Seronegative mFAS |
15.0; 5.2; 8.0; 6.7 | 0.0040 sig |
| SECONDARY Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on High Viral Load mFAS |
80.3; 89.2; 86.9; 88.0 | 0.0105 sig |
| SECONDARY Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on Seronegative mFAS |
81.3; 90.1; 89.9; 90.0 | 0.0275 sig |
| SECONDARY Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital Over Time Based on High Viral Load mFAS |
21.0; 15.2; 17.4; 16.3 | 0.1032 |
| SECONDARY Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital by Day 29 Based on Seronegative mFAS |
24.4; 11.6; 12.8; 12.2 | 0.00024 sig |
| SECONDARY Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death (ie, Overall Survival) by Day 29 Based on High Viral Load mFAS |
14.9; 7.7; 11.7; 9.7 | — |
| SECONDARY Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death (ie, Overall Survival) by Day 29 Based on Seronegative mFAS |
15.8; 5.6; 8.4; 7.0 | — |
| SECONDARY Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation by Day 29 Based on High Viral Load mFAS |
11.8; 6.3; 9.1; 7.7 | — |
| SECONDARY Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation by Day 29 Based on Seronegative mFAS |
10.6; 6.0; 7.9; 7.0 | — |
| SECONDARY Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation by Day 29 Based on High Viral Load mFAS |
19.1; 10.2; 15.0; 12.7 | — |
| SECONDARY Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation by Day 29 Based on Seronegative mFAS |
20.1; 8.4; 12.7; 10.7 | — |
| SECONDARY Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge From Hospital Based on High Viral Load mFAS |
5.0; 4.0; 4.0; 4.0 | 0.0533 |
| SECONDARY Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge From Hospital Based on Seronegative mFAS |
4.5; 4.0; 4.0; 4.0 | 0.0218 sig |
| SECONDARY Pooled Analysis (Phases 1/2/3 [Cohort 1] and Phase 2 [Cohorts 1A/2/3]): Number of Participants With Treatment-Emergent Serious Adverse Events |
203; 177; 181; 358 | — |
| SECONDARY Pooled Analysis (Phases 1/2/3 [Cohort 1] and Phase 2 [Cohorts 1A/2/3]): Number of Participants With Grade >=2 Infusion Related Reactions up to Day 4 |
6; 11; 15; 26 | — |
| SECONDARY Pooled Analysis (Phases 1/2/3 [Cohort 1] and Phase 2 [Cohorts 1A/2/3]): Number of Participants With Grade >=2 Hypersensitivity Reactions Up to Day 29 |
2; 5; 7; 12 | — |
| SECONDARY Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on Seronegative mFAS |
17.1; 8.8; 17.1; 13.0; 4.4; 3.3 | 0.2162 |
| SECONDARY Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 Through Day 29 Based on Seronegative mFAS |
19.4; 6.3; 10.0; 8.2; 9.3; 3.4 | 0.0223 sig |
| SECONDARY Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 Through Day 29 Based on Seronegative mFAS |
22.9; 7.5; 11.0; 9.3; 8.9; 3.3 | 0.0147 sig |
| SECONDARY Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on Seronegative mFAS |
70.0; 85.0; 84.1; 84.6; 90.0; 94.6 | 0.0481 sig |
| SECONDARY Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital by Day 29 Based on Seronegative mFAS |
27.1; 13.8; 14.6; 14.2; 22.2; 9.8 | 0.0500 |
| SECONDARY Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death up to Day 29 Based on Seronegative mFAS |
23.6; 7.8; 11.4; 9.6; 9.6; 3.6 | — |
| SECONDARY Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation by Day 29 Based on Seronegative mFAS |
18.2; 8.9; 17.6; 13.4; 4.7; 3.5 | — |
| SECONDARY Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation by Day 29 Based on Seronegative mFAS |
30.4; 12.7; 21.2; 17.0; 11.8; 4.7 | — |
| SECONDARY Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge From Hospital Based on Seronegative mFAS |
8.5; 5.0; 6.0; 6.0; 4.0; 3.0 | 0.0370 sig |
| SECONDARY Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: TWA Change From Baseline Viral Load (Seronegative mFAS) in NP Samples up to Day 11 Based on Seronegative mFAS |
-1.52; -2.03; -1.95; -2.00; -1.28; -1.88 | 0.0245 sig |
| SECONDARY Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: TWA Change From Baseline Viral Load (Seronegative mFAS) in NP Samples up to Day 29 |
-2.72; -3.68; -3.69; -3.69; -2.66; -3.31 | 0.0013 sig |
| SECONDARY Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: Change From Baseline in Viral Load (Seronegative mFAS) as Measured by RT-qPCR in NP Swabs Over Time |
-1.10; -0.90; -0.93; -0.92; -0.85; -1.03 | 0.0623 |
| SECONDARY Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: Percent Change From Baseline in Viral Load (Seronegative mFAS) as Measured by RT-qPCR in NP Swabs Over Time |
-92.04; -87.52; -88.15; -87.94; -85.92; -90.65 | 0.0623 |
| SECONDARY Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on High Viral Load mFAS |
17.5; 8.5; 16.9; 12.6; 3.9; 2.9 | 0.0481 sig |
| SECONDARY Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 to Day 29 Based on High Viral Load mFAS |
18.0; 10.2; 15.7; 12.8; 7.0; 3.1 | 0.0811 |
| SECONDARY Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 to Day 29 Based on High Viral Load mFAS |
20.6; 10.9; 16.9; 13.8; 6.8; 2.9 | 0.0389 sig |
| SECONDARY Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on High Viral Load mFAS |
72.2; 83.7; 78.8; 81.4; 90.3; 96.1 | 0.0364 sig |
| SECONDARY Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital Over Time Based on High Viral Load mFAS |
24.6; 18.6; 22.9; 20.6; 16.5; 10.8 | 0.2635 |
| SECONDARY Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death Over Time Based on High Viral Load mFAS |
21.1; 11.2; 17.9; 14.3; 7.2; 3.1 | — |
| SECONDARY Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation Over Time Based on High Viral Load mFAS |
18.1; 8.8; 18.0; 13.1; 4.0; 3.1 | — |
| SECONDARY Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation Over Time Based on High Viral Load mFAS |
27.2; 15.0; 24.4; 19.5; 9.1; 4.1 | — |
| SECONDARY Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge Based on High Viral Load mFAS |
7.0; 7.0; 7.0; 7.0; 4.0; 3.0 | — |
| SECONDARY Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Time-weighted Average (TWA) Change in Viral Load in Nasopharyngeal (NP) Samples Over Time Based on Seronegative mFAS |
-0.33; -0.40; -0.60; -0.50; -0.55; -0.86 | — |
| SECONDARY Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Change From Baseline as Measured by RT-qPCR in NP Swabs Over Time Based on Seronegative mFAS |
-0.66; -0.81; -1.08; -0.94; -1.18; -2.08 | — |
| SECONDARY Phase 1 [Cohort 1] and Phase 2 [Cohort 1]: Percentage of Participants Who Died or Went On Mechanical Ventilation by Day 29 Based on Seronegative mFAS |
26.9; 17.7; 22.0; 19.8 | — |
| SECONDARY Phase 1 [Cohort 1] and Phase 2 [Cohort 1]: Percentage of Participants Who Died or Went On Mechanical Ventilation by Day 29 Based on High Viral Load mFAS |
23.1; 23.4; 13.8; 18.5 | — |
| SECONDARY Phase 1 [Cohort 1]: Area Under the Concentration-Time Curve From Time 0 to 28 Days Post-dose (AUC0-28) |
3026; 9678; 2582; 8680 | — |
| SECONDARY Concentration at the End of Infusion (Ceoi) |
231; 776; 272; 847; 288; 848 | — |
| SECONDARY Concentration at Day 28 (C28) |
50.7; 166; 64.8; 174; 50.0; 144 | — |
| SECONDARY Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10933 |
489; 471; 484 | — |
| SECONDARY Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10987 |
467; 444; 463 | — |
| SECONDARY Immunogenicity as Measured by Neutralizing Antibody Status (NAb) to REGN10933 |
489; 471; 484; 1; 1; 1 | — |
| SECONDARY Immunogenicity as Measured by Neutralizing Antibody Status (NAb) to REGN10987 |
467; 444; 463; 9; 10; 4 | — |
Eligibility Criteria
Key Inclusion Criteria
- Has SARS-CoV-2-positive antigen or molecular diagnostic test (by validated SARS-CoV-2 antigen, RT-PCR, or other molecular diagnostic assay, using an appropriate sample such as NP, nasal, oropharyngeal [OP], or saliva) ≤72 hours prior to randomization and no alternative explanation for current clinical condition. A historical record of positive result from test conducted ≤72 hours prior to randomization is acceptable.
- Has symptoms consistent with COVID-19, as determined by investigator, with onset ≤10 days before randomization
- Hospitalized for ≤72 hours with at least 1 of the following at randomization; patients meeting more than one criterion will be categorized in the most severely affected category:
- Cohort 1A: With COVID-19 symptoms but not requiring supplemental oxygen
- Cohort 1: Maintains O2 saturation >93% on low-flow oxygen as defined in the protocol
- Cohort 2: High-intensity oxygen therapy without mechanical ventilation as defined in the protocol
- Cohort 3: On mechanical ventilation
Key Exclusion Criteria
- Phase 1 Only: Patients maintaining O2 saturation >94% on room air
- In the opinion of the investigator, unlikely to survive for >48 hours from screening
- Receiving extracorporeal membrane oxygenation (ECMO)
- Has new-onset stroke or seizure disorder during hospitalization
- Initiated on renal replacement therapy due to COVID-19
NOTE: Other protocol defined inclusion / exclusion criteria apply
Data sourced from ClinicalTrials.gov (NCT04426695). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.