Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for Hospitalized Adult Patients With COVID-19
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04426695 |
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Recruitment Status :
Active, not recruiting
First Posted : June 11, 2020
Last Update Posted : May 12, 2021
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The primary objectives are:
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 Phase 2 (Cohort 1A)
- To evaluate the clinical efficacy 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 Phase 3 (Cohort 1 and Cohort 1A)
- To evaluate the clinical efficacy of REGN10933+REGN10987 compared to placebo, as measured by death or mechanical ventilation
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| COVID-19 | Drug: REGN10933+REGN10987 combination therapy Drug: Placebo | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 6900 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Phase 1/Phase 2/Phase 3 |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| 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 Hospitalized Patients With COVID-19 |
| Actual Study Start Date : | June 10, 2020 |
| Actual Primary Completion Date : | May 7, 2021 |
| Estimated Study Completion Date : | June 4, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: On Low-Flow Oxygen
Cohort 1 (C1): O2 saturation >93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device
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Drug: REGN10933+REGN10987 combination therapy
Administered intravenously (IV) single dose
Other Names:
Drug: Placebo Placebo IV Single Dose |
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Experimental: With COVID-19 symptoms but not requiring supplemental O2
Cohort 1A (C1A): With COVID-19 symptoms but not requiring supplemental oxygen
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Drug: REGN10933+REGN10987 combination therapy
Administered intravenously (IV) single dose
Other Names:
Drug: Placebo Placebo IV Single Dose |
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Experimental: High O2 No Mechanical Ventilation
Cohort 2 (C2): On high-intensity oxygen (O2) therapy but not on mechanical ventilation
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Drug: REGN10933+REGN10987 combination therapy
Administered intravenously (IV) single dose
Other Names:
Drug: Placebo Placebo IV Single Dose |
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Experimental: On Mechanical Ventilation
Cohort 3 (C3): On mechanical ventilation
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Drug: REGN10933+REGN10987 combination therapy
Administered intravenously (IV) single dose
Other Names:
Drug: Placebo Placebo IV Single Dose |
- Incidence of death or required mechanical ventilation [ Time Frame: Through day 169 ]
Primary:
Through Day 169: Phase 1/2: C1 (Futility) Through Day 57: Phase 2: C1A (Clinical Efficacy) Timeframe determined based on Phase 1/2 data: Phase 3, C1, C1A (Clinical Efficacy)
Secondary (Clinical Efficacy):
Through Day 169: Phase 1/2: C1 Through Day 57: Phase 2: C2 Timeframe determined based on Phase 1/2 data: Phase 3: C1, C1A
- Proportion of patients with treatment-emergent Serious Adverse Events (SAEs) [ Time Frame: Through Day 169 ]
Primary:
Through Day 169: Phase 1/2: C1 Through Day 57: Phase 2, C1A
Secondary:
Through Day 57: Phase 2: C2, C3
- Proportion of patients with infusion-related reactions [ Time Frame: Through Day 4 ]Primary: Phase 1/2: C1, Phase 2: C1A Secondary: Phase 2: C2, C3
- Proportion of patients with hypersensitivity reactions [ Time Frame: Through Day 29 ]Primary: Phase 1/2: C1, Phase 2: C1A Secondary: Phase 2: C2, C3
- Time-weighted average change from baseline in viral load as measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples [ Time Frame: Baseline to Day 7 ]Phase 1/2: C1, Phase 2: C1A, C2, C3, Phase 3: C1, C1A
- Time-weighted average change from baseline in viral load as measured by RT-qPCR in NP swab samples [ Time Frame: Baseline up to Day 11 ]Phase 1/2: C1, Phase 2: C1A, C2, C3, Phase 3: C1, C1A
- Time-weighted average change from baseline in viral load as measured by RT-qPCR in NP swab samples [ Time Frame: Baseline up to Day 29 ]Phase 1/2: C1, Phase 2: C1A, C2, C3, Phase 3: C1, C1A
- Change from baseline in viral load as measured by RT-qPCR in NP swabs [ Time Frame: Baseline up to Day 29 ]Phase 1/2: C1, Phase 2: C1A, C2, C3, Phase 3: C1, C1A
- Time to sustained negative RT-qPCR in NP swab samples [ Time Frame: Up To Day 29 ]
Negative RT-qPCR with no subsequent positive
Phase 1/2: C1, Phase 2; C1A, C2, C3, Phase 3: C1, C1A
- Incidence of deaths due to any cause [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 57: Phase 2: C1A, C2, C3
- Incidence of required mechanical ventilation [ Time Frame: Through Day 29 ]Through Day 29: Phase 1/2: C1, Phase 2: C1A, C2, Phase 3: C1, C1A
- Proportion of patients who died or went on mechanical ventilation [ Time Frame: By Day 29 ]Phase 1/2: C1, Phase 2: C1A, C2, Phase 3: C1, C1A
- Proportion of patients who died [ Time Frame: By Day 29 ]Phase 1/2: C1, Phase 2: C1A, C2, C3, Phase 3: C1, C1A
- Proportion of patients who went on mechanical ventilation [ Time Frame: By Day 29 ]Phase 1/2: C1, Phase 2: C1A, C2, Phase 3: C1, C1A
- Time to discharge [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Serum concentration of REGN10933 over time [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Serum concentration of REGN10987 over time [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of pharmacokinetic (PK) parameter: maximum serum concentration observed (Cmax) of REGN10933 [ Time Frame: Through day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of PK parameter: maximum serum concentration observed (Cmax) of REGN10987 [ Time Frame: Through day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) for REGN10933 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) for REGN10987 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of PK parameter: Time to Cmax (tmax) for REGN10933 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of PK parameter: Time to Cmax (tmax) for REGN10987 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of PK parameter: Area Under the Curve (AUC) computed from time zero to the time of the last positive concentration (AUClast) for REGN10933 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of PK parameter: AUC computed from time zero to the time of the last positive concentration (AUClast) for REGN10987 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of PK parameter: AUC from time zero extrapolated to infinity (AUCinf) for REGN10933 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of PK parameter: AUC from time zero extrapolated to infinity (AUCinf) for REGN10987 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of PK parameter: AUCinf-to-dose ratio (AUCinf/dose) of REGN10933 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of PK parameter: AUCinf-to-dose ratio (AUCinf/dose) of REGN10987 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of PK parameter: Observed terminal half-life [t1/2] for REGN10933 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of PK parameter: Observed terminal half-life [t1/2] of REGN10987 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of PK parameter: Clearance (CL) for REGN10933 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of PK parameter: Clearance (CL) of REGN10987 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of PK parameter: Volume of distribution at steady state (Vss) of REGN10933 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of PK parameter: Volume of distribution at steady state (Vss) of REGN10987 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of PK parameter: Mean residence time (MRT) of REGN10933 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Assessment of PK parameter: Mean residence time (MRT) of REGN10987 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Incidence of anti-drug antibodies (ADA) to REGN10933 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
- Incidence of anti-drug antibodies (ADA) to REGN10987 [ Time Frame: Through Day 169 ]
Through Day 169: Phase 1/2: C1, Phase 3: C1, C1A
Through Day 29: Phase 2: C1A, C2, C3
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04426695
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| Study Director: | Clinical Trial Management | Regeneron Pharmaceuticals |
| Responsible Party: | Regeneron Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT04426695 |
| Other Study ID Numbers: |
R10933-10987-COV-2066 2020-002537-15 ( EudraCT Number ) |
| First Posted: | June 11, 2020 Key Record Dates |
| Last Update Posted: | May 12, 2021 |
| Last Verified: | March 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (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). |
| URL: | https://vivli.org/ |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Coronavirus disease 2019 (COVID-19) Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) coronavirus acute respiratory distress syndrome |