SARS-CoV-2
Conditions
Keywords
COVID-19, Non-hospitalized, Low-risk, Symptomatic, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), coronavirus
Brief summary
Primary Objectives Phase 1 (Safety and Tolerability) • Evaluate the safety and tolerability of REGN14256+imdevimab and REGN14256 monotherapy, as measured by treatment-emergent adverse events (TEAEs), injection-site reactions (ISRs), and hypersensitivity reactions Phase 1/2 (Virologic Efficacy) • Evaluate the virologic efficacy of REGN14256+imdevimab and REGN14256 monotherapy compared to placebo, as measured by time-weighted average (TWA) change from baseline in viral load through day 7 Phase 1/2/3 (Clinical Efficacy) • Evaluate the clinical efficacy of REGN14256+imdevimab compared to placebo, as measured by COVID-19 symptoms resolution Secondary Objectives Phase 1 (Safety and Tolerability) • Evaluate the safety and tolerability of REGN14256+imdevimab and REGN14256 monotherapy, as measured by treatment-emergent serious adverse events (SAEs) Phase 2 and Phase 3 (Safety and Tolerability) • Evaluate the safety and tolerability of REGN14256+imdevimab and REGN14256 monotherapy, as measured by TEAEs, ISRs, hypersensitivity reactions, and SAEs Phase 1, Phase 2, and Phase 3 (Virologic Efficacy, Drug Concentration, and Immunogenicity) * Evaluate additional indicators of virologic efficacy of REGN14256+imdevimab and REGN14256 monotherapy * Characterize the concentration-time profile of REGN14256 administered in combination with imdevimab or alone as a monotherapy * Assess the immunogenicity of REGN14256 administered in combination with imdevimab or alone as a monotherapy
Interventions
DRUGREGN14256
Sub-cutaneous (SC) single dose
DRUGimdevimab
SC single dose
SC single dose
DRUGPlacebo
SC single dose
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Phase1/Phase2/Phase3
Eligibility
Sex/Gender
ALL
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Phase 1 will enroll adult patients (≥18 years of age), Phase 2 will enroll adult patients, Phase 3 will enroll adult patients and an additional adolescent cohort of patients (≥12 and \<18 years of age) Key Inclusion Criteria: 1. For the adolescent cohort in Phase 3 only: Weighs ≥40 kg at randomization 2. Has SARS-CoV-2-positive antigen or molecular diagnostic test (by validated SARSCoV-2 antigen, RT-PCR, or other molecular diagnostic assay, using an appropriate sample such as nasopharyngeal \[NP\], nasal, oropharyngeal \[OP\], or saliva) ≤72 hours prior to randomization. A historical record of a positive result is acceptable as long as the sample was collected ≤72 hours prior to randomization 3. Has symptoms consistent with COVID-19 (as determined by the investigator) with onset ≤7 days before randomization, and doesn't have a medical condition or other factors associated with high risk for progression to severe COVID-19 as outlined in the
Exclusion criteria
4. Maintains O2 saturation ≥93% on room air Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Emergent Adverse Events (TEAEs) | Through Day 29 | Phase 1 |
| Severity of TEAEs | Through Day 29 | Severity was based on Grading. Grade 1 was less severe. Grade 5 was more severe. 1. \- Mild; Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated 2. \- Moderate; Minimal, local, or noninvasive intervention indicated; limiting age appropriate instrumental activities of daily living (ADL) 3. \- Severe; Severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; ADL2 limiting self-care 4. \- Life-threatening; Life threatening consequences; urgent intervention indicated 5. \- Death; Death related to adverse events |
| Percentage of Participants With Injection-site Reactions (ISRs) | Through Day 169 | Phase 1 only |
| Severity of ISRs (Injection Site Reactions) | Through Day 29 | Severity was based on Grading. Grade 1 was less severe. Grade 5 was more severe. Grade 1 - Tenderness with or without associated symptoms (eg, warmth, erythema, itching) Grade 2 - Pain; lipodystrophy; edema; phlebitis Grade 3 - Ulceration or necrosis; severe tissue damage; operative intervention indicated Grade 4 - Life-threatening consequences; urgent intervention indicated Grade 5 - Death |
| Percentage of Participants With Hypersensitivity Reactions | Through Day 169 | Phase 1 |
| Severity of Hypersensitivity Reactions Over Time | Through Day 169 | Grade 1 - Systemic intervention not indicated. Grade 2 - Oral intervention indicated Grade 3 - Bronchospasm; hospitalization indicated for clinical sequelae; intravenous intervention indicated Grade 4 - Life-threatening consequences; urgent intervention indicated Grade 5 - Death |
| Time-weighted Average (TWA) Daily Change From Baseline in Viral Load (log10 Copies/mL) | Day 1 to day 7 | Phase 1 Measured by SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) | Through Day 169 | Phase 1 |
| Time-weighted Average Change From Baseline in Viral Load | Through Day 169 | Phase 2 and Phase 3 Time-weighted average (TWA) daily change from baseline in viral load (log10 copies/mL) as measured by SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples. |
| Change From Baseline in Viral Load (Phase 1) | Through Day 7 | Phase 1 Change from baseline in viral load (log10 copies/mL) as measured by SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples. |
| Change From Baseline in Viral Load | Through Day 7 | Phase 2, and Phase 3 As measured by RT-qPCR in NP samples |
| Percentage of Participants With Viral Loads Below the Limit of Detection | Through Day 169 | Phase 1, Phase 2, and Phase 3 |
| Percentage of Participants With Treatment-emergent SAEs (Serious Adverse Events) | Through Day 169 | Phase 2 and Phase 3 |
| Concentrations of REGN14256 in Serum Over Time | Through Day 169 | Phase 2 and Phase 3 |
| Concentrations of Imdevimab in Serum Over Time (Phase 1) | Through Day 169 | Phase 1 |
| Concentrations of Imdevimab in Serum Over Time | Through Day 169 | Phase 2 and Phase 3 |
| Incidence and Titer of Anti-drug Antibodies (ADA) to REGN14256 Over Time | Through Day 169 | Phase 1, Phase 2, and Phase 3 |
| Incidence and Titer of ADA to Imdevimab Over Time | Through Day 169 | Phase 1, Phase 2, and Phase 3 |
| Concentrations of REGN14256 in Serum Over Time (Phase 1) | Through Day 169 | Phase 1 |
| TEAEs (Treatment-Emergent Adverse Events) | Through Day 29 | Phase 2 and Phase 3 |
| Severity of TEAEs (Treatment-Emergent Adverse Event) | Through Day 29 | Phase 2 and Phase 3 |
| Percentage of Participants With ISRs (Injection-Site Reactions) | Through Day 169 | Phase 2 and Phase 3 |
| Severity of ISRs (Injection-Site Reactions) | Through Day 169 | Phase 2 and Phase 3 |
| Percentage of Participants With Hypersensitivity Reactions | Through Day 169 | Phase 2 and Phase 3 |
| Severity of Hypersensitivity Reactions Over Time | Through Day 169 | Phase 2 and Phase 3 |
Countries
United States
Participant flow
Recruitment details
The study was initiated in November 2021, however, due to the reduced activity of REGN14256+imdevimab against the emerging Omicron variant and not due to any safety concerns, study enrollment was paused and later terminated. As a result, only 25 participants were randomized into the phase 1 portion of the study and the phase 2 and phase 3 portions of the study were never opened.
Pre-assignment details
The study was initiated in November 2021, however, due to the reduced activity of REGN14256+imdevimab against the emerging Omicron variant and not due to any safety concerns, study enrollment was paused and later terminated. As a result, only 25 participants were randomized into the phase 1 portion of the study and the phase 2 and phase 3 portions of the study were never opened
Participants by arm
| Arm | Count |
|---|---|
| Placebo Phase 1 only. Phase 2 and Phase 3 portions of the study were never opened | 4 |
| Imdevimab (600 mg SC) Phase 1 only. Phase 2 and Phase 3 portions of the study were never opened | 5 |
| REGN14256 (600 mg SC) Phase 1 only. Phase 2 and Phase 3 portions of the study were never opened | 6 |
| Casirivimab + Imdevimab (1200 mg SC) Phase 1 only. Phase 2 and Phase 3 portions of the study were never opened | 6 |
| REGN14256 + Imdevimab (1200 mg SC) Phase 1 only. Phase 2 and Phase 3 portions of the study were never opened | 4 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Subject decision | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Imdevimab (600 mg SC) | REGN14256 (600 mg SC) | Casirivimab + Imdevimab (1200 mg SC) | REGN14256 + Imdevimab (1200 mg SC) | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 25.8 Years STANDARD_DEVIATION 1.5 | 50.4 Years STANDARD_DEVIATION 14.05 | 38.2 Years STANDARD_DEVIATION 19.81 | 30.3 Years STANDARD_DEVIATION 7.87 | 42.0 Years STANDARD_DEVIATION 9.9 | 37.4 Years STANDARD_DEVIATION 14.63 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 3 Participants | 6 Participants | 3 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 5 Participants | 5 Participants | 5 Participants | 4 Participants | 22 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 11 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 4 Participants | 3 Participants | 2 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 5 | 0 / 6 | 0 / 4 | 0 / 6 |
| other Total, other adverse events | 1 / 3 | 2 / 5 | 1 / 6 | 2 / 4 | 1 / 6 |
| serious Total, serious adverse events | 1 / 3 | 1 / 5 | 0 / 6 | 0 / 4 | 0 / 6 |
Outcome results
Primary
Percentage of Participants With Hypersensitivity Reactions
Phase 1
Time frame: Through Day 169
Population: The study was terminated in the Phase 1 portion of the study. The Safety Analysis Set (SAF) includes all randomized participants who received any study drug; it is based on the treatment received. Only Phase 1 data was collected. Phase 2 and Phase 3 portions of the study were never opened.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Hypersensitivity Reactions | 0 Percentage of Participants |
| Imdevimab (600 mg SC) | Percentage of Participants With Hypersensitivity Reactions | 0 Percentage of Participants |
| REGN14256 (600 mg SC) | Percentage of Participants With Hypersensitivity Reactions | 0 Percentage of Participants |
| Casirivimab + Imdevimab (1200 mg SC) | Percentage of Participants With Hypersensitivity Reactions | 0 Percentage of Participants |
| REGN14256 + Imdevimab (1200 mg SC) | Percentage of Participants With Hypersensitivity Reactions | 0 Percentage of Participants |
Primary
Percentage of Participants With Injection-site Reactions (ISRs)
Phase 1 only
Time frame: Through Day 169
Population: The Safety Analysis Set (SAF) includes all randomized participants who received any study drug; it is based on the treatment received. The study was terminated during Phase 1. Only Phase 1 data was collected. Phase 2 and Phase 3 portions of the study were never opened.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Injection-site Reactions (ISRs) | 0 Percentage of Participants |
| Imdevimab (600 mg SC) | Percentage of Participants With Injection-site Reactions (ISRs) | 0 Percentage of Participants |
| REGN14256 (600 mg SC) | Percentage of Participants With Injection-site Reactions (ISRs) | 0 Percentage of Participants |
| Casirivimab + Imdevimab (1200 mg SC) | Percentage of Participants With Injection-site Reactions (ISRs) | 0 Percentage of Participants |
| REGN14256 + Imdevimab (1200 mg SC) | Percentage of Participants With Injection-site Reactions (ISRs) | 25.0 Percentage of Participants |
Primary
Severity of Hypersensitivity Reactions Over Time
Grade 1 - Systemic intervention not indicated. Grade 2 - Oral intervention indicated Grade 3 - Bronchospasm; hospitalization indicated for clinical sequelae; intravenous intervention indicated Grade 4 - Life-threatening consequences; urgent intervention indicated Grade 5 - Death
Time frame: Through Day 169
Population: The study was terminated in the Phase 1 portion of the study. The Safety Analysis Set (SAF) includes all randomized participants who received any study drug; it is based on the treatment received. Phase 2 and Phase 3 portions of the study were never opened.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 4 | 0 Events |
| Placebo | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 1 | 0 Events |
| Placebo | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 5 | 0 Events |
| Placebo | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 2 | 0 Events |
| Placebo | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 3 | 0 Events |
| Imdevimab (600 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 4 | 0 Events |
| Imdevimab (600 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 3 | 0 Events |
| Imdevimab (600 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 2 | 0 Events |
| Imdevimab (600 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 5 | 0 Events |
| Imdevimab (600 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 1 | 0 Events |
| REGN14256 (600 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 3 | 0 Events |
| REGN14256 (600 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 1 | 0 Events |
| REGN14256 (600 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 2 | 0 Events |
| REGN14256 (600 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 4 | 0 Events |
| REGN14256 (600 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 5 | 0 Events |
| Casirivimab + Imdevimab (1200 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 5 | 0 Events |
| Casirivimab + Imdevimab (1200 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 1 | 0 Events |
| Casirivimab + Imdevimab (1200 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 4 | 0 Events |
| Casirivimab + Imdevimab (1200 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 3 | 0 Events |
| Casirivimab + Imdevimab (1200 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 2 | 0 Events |
| REGN14256 + Imdevimab (1200 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 3 | 0 Events |
| REGN14256 + Imdevimab (1200 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 4 | 0 Events |
| REGN14256 + Imdevimab (1200 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 1 | 0 Events |
| REGN14256 + Imdevimab (1200 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 5 | 0 Events |
| REGN14256 + Imdevimab (1200 mg SC) | Severity of Hypersensitivity Reactions Over Time | With at least one Grade 2 | 0 Events |
Primary
Severity of ISRs (Injection Site Reactions)
Severity was based on Grading. Grade 1 was less severe. Grade 5 was more severe. Grade 1 - Tenderness with or without associated symptoms (eg, warmth, erythema, itching) Grade 2 - Pain; lipodystrophy; edema; phlebitis Grade 3 - Ulceration or necrosis; severe tissue damage; operative intervention indicated Grade 4 - Life-threatening consequences; urgent intervention indicated Grade 5 - Death
Time frame: Through Day 29
Population: The Safety Analysis Set (SAF) includes all randomized participants who received any study drug; it is based on the treatment received. The study was terminated during Phase 1. Only Phase 1 data was collected. Phase 2 and Phase 3 portions of the study were never opened.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Severity of ISRs (Injection Site Reactions) | With at least one Grade 4 ISR | 0 Events |
| Placebo | Severity of ISRs (Injection Site Reactions) | With at least one Grade 1 ISR | 0 Events |
| Placebo | Severity of ISRs (Injection Site Reactions) | With at least one Grade 5 ISR | 0 Events |
| Placebo | Severity of ISRs (Injection Site Reactions) | With at least one Grade 2 ISR | 0 Events |
| Placebo | Severity of ISRs (Injection Site Reactions) | With at least one Grade 3 ISR | 0 Events |
| Imdevimab (600 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 4 ISR | 0 Events |
| Imdevimab (600 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 3 ISR | 0 Events |
| Imdevimab (600 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 2 ISR | 0 Events |
| Imdevimab (600 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 5 ISR | 0 Events |
| Imdevimab (600 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 1 ISR | 0 Events |
| REGN14256 (600 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 3 ISR | 0 Events |
| REGN14256 (600 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 1 ISR | 0 Events |
| REGN14256 (600 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 2 ISR | 0 Events |
| REGN14256 (600 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 4 ISR | 0 Events |
| REGN14256 (600 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 5 ISR | 0 Events |
| Casirivimab + Imdevimab (1200 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 5 ISR | 0 Events |
| Casirivimab + Imdevimab (1200 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 1 ISR | 0 Events |
| Casirivimab + Imdevimab (1200 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 4 ISR | 0 Events |
| Casirivimab + Imdevimab (1200 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 3 ISR | 0 Events |
| Casirivimab + Imdevimab (1200 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 2 ISR | 0 Events |
| REGN14256 + Imdevimab (1200 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 3 ISR | 0 Events |
| REGN14256 + Imdevimab (1200 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 4 ISR | 0 Events |
| REGN14256 + Imdevimab (1200 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 1 ISR | 1 Events |
| REGN14256 + Imdevimab (1200 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 5 ISR | 0 Events |
| REGN14256 + Imdevimab (1200 mg SC) | Severity of ISRs (Injection Site Reactions) | With at least one Grade 2 ISR | 0 Events |
Primary
Severity of TEAEs
Severity was based on Grading. Grade 1 was less severe. Grade 5 was more severe. 1. \- Mild; Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated 2. \- Moderate; Minimal, local, or noninvasive intervention indicated; limiting age appropriate instrumental activities of daily living (ADL) 3. \- Severe; Severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; ADL2 limiting self-care 4. \- Life-threatening; Life threatening consequences; urgent intervention indicated 5. \- Death; Death related to adverse events
Time frame: Through Day 29
Population: The study was terminated in the Phase 1 portion of the study. The Safety Analysis Set (SAF) includes all randomized participants who received any study drug; it is based on the treatment received. Only Phase 1 data was collected. Phase 2 and Phase 3 portions of the study were never opened.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Severity of TEAEs | With at least one Grade 4 TEAE | 0 Participants |
| Placebo | Severity of TEAEs | With at least one Grade 3 TEAE | 0 Participants |
| Placebo | Severity of TEAEs | With at least one Grade 1 TEAE | 0 Participants |
| Placebo | Severity of TEAEs | With at least one Grade 5 TEAE | 0 Participants |
| Placebo | Severity of TEAEs | With at least one Grade 2 TEAE | 1 Participants |
| Imdevimab (600 mg SC) | Severity of TEAEs | With at least one Grade 1 TEAE | 2 Participants |
| Imdevimab (600 mg SC) | Severity of TEAEs | With at least one Grade 4 TEAE | 0 Participants |
| Imdevimab (600 mg SC) | Severity of TEAEs | With at least one Grade 3 TEAE | 1 Participants |
| Imdevimab (600 mg SC) | Severity of TEAEs | With at least one Grade 2 TEAE | 0 Participants |
| Imdevimab (600 mg SC) | Severity of TEAEs | With at least one Grade 5 TEAE | 0 Participants |
| REGN14256 (600 mg SC) | Severity of TEAEs | With at least one Grade 4 TEAE | 0 Participants |
| REGN14256 (600 mg SC) | Severity of TEAEs | With at least one Grade 1 TEAE | 1 Participants |
| REGN14256 (600 mg SC) | Severity of TEAEs | With at least one Grade 2 TEAE | 0 Participants |
| REGN14256 (600 mg SC) | Severity of TEAEs | With at least one Grade 3 TEAE | 0 Participants |
| REGN14256 (600 mg SC) | Severity of TEAEs | With at least one Grade 5 TEAE | 0 Participants |
| Casirivimab + Imdevimab (1200 mg SC) | Severity of TEAEs | With at least one Grade 4 TEAE | 0 Participants |
| Casirivimab + Imdevimab (1200 mg SC) | Severity of TEAEs | With at least one Grade 1 TEAE | 1 Participants |
| Casirivimab + Imdevimab (1200 mg SC) | Severity of TEAEs | With at least one Grade 2 TEAE | 0 Participants |
| Casirivimab + Imdevimab (1200 mg SC) | Severity of TEAEs | With at least one Grade 5 TEAE | 0 Participants |
| Casirivimab + Imdevimab (1200 mg SC) | Severity of TEAEs | With at least one Grade 3 TEAE | 0 Participants |
| REGN14256 + Imdevimab (1200 mg SC) | Severity of TEAEs | With at least one Grade 1 TEAE | 2 Participants |
| REGN14256 + Imdevimab (1200 mg SC) | Severity of TEAEs | With at least one Grade 2 TEAE | 0 Participants |
| REGN14256 + Imdevimab (1200 mg SC) | Severity of TEAEs | With at least one Grade 4 TEAE | 0 Participants |
| REGN14256 + Imdevimab (1200 mg SC) | Severity of TEAEs | With at least one Grade 3 TEAE | 0 Participants |
| REGN14256 + Imdevimab (1200 mg SC) | Severity of TEAEs | With at least one Grade 5 TEAE | 0 Participants |
Primary
Time-weighted Average (TWA) Daily Change From Baseline in Viral Load (log10 Copies/mL)
Phase 1 Measured by SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples
Time frame: Day 1 to day 7
Population: The modified full analysis set (mFAS) includes all randomized patients with a positive central lab determined SARS-CoV-2 RT-qPCR result from nasopharyngeal (NP) swab samples at randomization and is based on the treatment received. The study was terminated, and Phase 2 and Phase 3 portions of the study were never opened.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time-weighted Average (TWA) Daily Change From Baseline in Viral Load (log10 Copies/mL) | -4.02 log10 copies/mL | Standard Deviation 1.461 |
| Imdevimab (600 mg SC) | Time-weighted Average (TWA) Daily Change From Baseline in Viral Load (log10 Copies/mL) | -2.28 log10 copies/mL | Standard Deviation 0.286 |
| REGN14256 (600 mg SC) | Time-weighted Average (TWA) Daily Change From Baseline in Viral Load (log10 Copies/mL) | -2.30 log10 copies/mL | Standard Deviation 0.964 |
| Casirivimab + Imdevimab (1200 mg SC) | Time-weighted Average (TWA) Daily Change From Baseline in Viral Load (log10 Copies/mL) | -2.72 log10 copies/mL | Standard Deviation 1.517 |
| REGN14256 + Imdevimab (1200 mg SC) | Time-weighted Average (TWA) Daily Change From Baseline in Viral Load (log10 Copies/mL) | -1.76 log10 copies/mL | Standard Deviation 0.003 |
Primary
Treatment Emergent Adverse Events (TEAEs)
Phase 1
Time frame: Through Day 29
Population: The study was terminated in the Phase 1 portion of the study. The Safety Analysis Set (SAF) includes all randomized participants who received any study drug; it is based on the treatment received. Only Phase 1 data was collected. Phase 2 and Phase 3 portions of the study were never opened.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Treatment Emergent Adverse Events (TEAEs) | 1 Events |
| Imdevimab (600 mg SC) | Treatment Emergent Adverse Events (TEAEs) | 3 Events |
| REGN14256 (600 mg SC) | Treatment Emergent Adverse Events (TEAEs) | 1 Events |
| Casirivimab + Imdevimab (1200 mg SC) | Treatment Emergent Adverse Events (TEAEs) | 1 Events |
| REGN14256 + Imdevimab (1200 mg SC) | Treatment Emergent Adverse Events (TEAEs) | 2 Events |
Secondary
Change From Baseline in Viral Load
Phase 2, and Phase 3 As measured by RT-qPCR in NP samples
Time frame: Through Day 7
Population: The study was terminated, and Phase 2 and Phase 3 portions of the study were never opened. No data collected.
Secondary
Change From Baseline in Viral Load (Phase 1)
Phase 1 Change from baseline in viral load (log10 copies/mL) as measured by SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples.
Time frame: Through Day 7
Population: The modified full analysis set (mFAS) includes all randomized patients with a positive central lab determined SARS-CoV-2 RT-qPCR result from nasopharyngeal (NP) swab samples at randomization and is based on the treatment received. The study was terminated, and Phase 2 and Phase 3 portions of the study were never opened
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Viral Load (Phase 1) | Change from Baseline to Day 3 | -3.93 log10 copies/mL | Standard Deviation 2.691 |
| Placebo | Change From Baseline in Viral Load (Phase 1) | Change from Baseline to Day 7 | -5.76 log10 copies/mL | Standard Deviation 2.22 |
| Placebo | Change From Baseline in Viral Load (Phase 1) | Change from Baseline to Day 5 | -5.25 log10 copies/mL | Standard Deviation 1.4 |
| Imdevimab (600 mg SC) | Change From Baseline in Viral Load (Phase 1) | Change from Baseline to Day 5 | -3.74 log10 copies/mL | Standard Deviation 1.585 |
| Imdevimab (600 mg SC) | Change From Baseline in Viral Load (Phase 1) | Change from Baseline to Day 3 | -2.14 log10 copies/mL | Standard Deviation 0.251 |
| Imdevimab (600 mg SC) | Change From Baseline in Viral Load (Phase 1) | Change from Baseline to Day 7 | -3.02 log10 copies/mL | Standard Deviation 1.115 |
| REGN14256 (600 mg SC) | Change From Baseline in Viral Load (Phase 1) | Change from Baseline to Day 5 | -3.28 log10 copies/mL | Standard Deviation 1.085 |
| REGN14256 (600 mg SC) | Change From Baseline in Viral Load (Phase 1) | Change from Baseline to Day 3 | -1.60 log10 copies/mL | Standard Deviation 1.598 |
| REGN14256 (600 mg SC) | Change From Baseline in Viral Load (Phase 1) | Change from Baseline to Day 7 | -4.01 log10 copies/mL | Standard Deviation 2 |
| Casirivimab + Imdevimab (1200 mg SC) | Change From Baseline in Viral Load (Phase 1) | Change from Baseline to Day 3 | -2.27 log10 copies/mL | Standard Deviation 1.097 |
| Casirivimab + Imdevimab (1200 mg SC) | Change From Baseline in Viral Load (Phase 1) | Change from Baseline to Day 7 | -4.31 log10 copies/mL | Standard Deviation 2.121 |
| Casirivimab + Imdevimab (1200 mg SC) | Change From Baseline in Viral Load (Phase 1) | Change from Baseline to Day 5 | -3.73 log10 copies/mL | Standard Deviation 2.677 |
| REGN14256 + Imdevimab (1200 mg SC) | Change From Baseline in Viral Load (Phase 1) | Change from Baseline to Day 5 | -1.88 log10 copies/mL | — |
| REGN14256 + Imdevimab (1200 mg SC) | Change From Baseline in Viral Load (Phase 1) | Change from Baseline to Day 3 | 0.23 log10 copies/mL | — |
| REGN14256 + Imdevimab (1200 mg SC) | Change From Baseline in Viral Load (Phase 1) | Change from Baseline to Day 7 | -5.37 log10 copies/mL | Standard Deviation 2.617 |
Secondary
Concentrations of Imdevimab in Serum Over Time
Phase 2 and Phase 3
Time frame: Through Day 169
Population: The study was terminated, and Phase 2 and Phase 3 portions of the study were never opened. No data collected.
Secondary
Concentrations of Imdevimab in Serum Over Time (Phase 1)
Phase 1
Time frame: Through Day 169
Population: The PK analysis set includes all treated participants who received imdevimab and who had at least 1 non-missing result of respective analyte following the first dose of imdevimab. The study was terminated, data was not collected for Phase 2 and Phase 3, as these portions were never opened.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Pre-dose | 2.46 mg/L | Standard Deviation 3.59 |
| Placebo | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 2 | 28.4 mg/L | Standard Deviation 6.08 |
| Placebo | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 1 | 19.7 mg/L | Standard Deviation 9.74 |
| Placebo | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Post-dose | 3.43 mg/L | Standard Deviation 3.13 |
| Placebo | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 6 | 42.7 mg/L | Standard Deviation 16.8 |
| Placebo | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 119 | 1.72 mg/L | Standard Deviation 1.06 |
| Placebo | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 89 | 3.26 mg/L | Standard Deviation 1.8 |
| Placebo | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 28 | 18.9 mg/L | Standard Deviation 9.94 |
| Placebo | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 59 | 7.66 mg/L | Standard Deviation 3.68 |
| Imdevimab (600 mg SC) | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 28 | 27.9 mg/L | Standard Deviation 8.34 |
| Imdevimab (600 mg SC) | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 59 | 10.3 mg/L | Standard Deviation 4.4 |
| Imdevimab (600 mg SC) | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 89 | 4.37 mg/L | Standard Deviation 2.12 |
| Imdevimab (600 mg SC) | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 119 | 2.60 mg/L | Standard Deviation 1.52 |
| Imdevimab (600 mg SC) | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 1 | 31.2 mg/L | Standard Deviation 10.5 |
| Imdevimab (600 mg SC) | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 2 | 40.7 mg/L | Standard Deviation 11.8 |
| Imdevimab (600 mg SC) | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 6 | 52.2 mg/L | Standard Deviation 16.3 |
| Imdevimab (600 mg SC) | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Post-dose | 3.06 mg/L | Standard Deviation 2.36 |
| Imdevimab (600 mg SC) | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Pre-dose | 0.398 mg/L | Standard Deviation 0.976 |
| REGN14256 (600 mg SC) | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 119 | 2.68 mg/L | Standard Deviation 0.91 |
| REGN14256 (600 mg SC) | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Pre-dose | 0.360 mg/L | Standard Deviation 0.72 |
| REGN14256 (600 mg SC) | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Post-dose | 9.03 mg/L | Standard Deviation 6.47 |
| REGN14256 (600 mg SC) | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 1 | 27.9 mg/L | Standard Deviation 21 |
| REGN14256 (600 mg SC) | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 2 | 31.9 mg/L | Standard Deviation 19.2 |
| REGN14256 (600 mg SC) | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 6 | 38.8 mg/L | Standard Deviation 7.59 |
| REGN14256 (600 mg SC) | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 28 | 20.8 mg/L | Standard Deviation 12.2 |
| REGN14256 (600 mg SC) | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 89 | 3.73 mg/L | Standard Deviation 2.46 |
| REGN14256 (600 mg SC) | Concentrations of Imdevimab in Serum Over Time (Phase 1) | Day 59 | 7.18 mg/L | Standard Deviation 3.75 |
Secondary
Concentrations of REGN14256 in Serum Over Time
Phase 2 and Phase 3
Time frame: Through Day 169
Population: The study was terminated, and Phase 2 and Phase 3 portions of the study were never opened. No data collected.
Secondary
Concentrations of REGN14256 in Serum Over Time (Phase 1)
Phase 1
Time frame: Through Day 169
Population: The PK analysis set includes all treated participants who received REGN14256 and who had at least 1 non-missing result of respective analyte following the first dose of REGN14256. The study was terminated, data was not collected for Phase 2 and Phase 3, as these portions were never opened.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Concentrations of REGN14256 in Serum Over Time (Phase 1) | Post-dose | 3.45 mg/L | Standard Deviation 4.36 |
| Placebo | Concentrations of REGN14256 in Serum Over Time (Phase 1) | Day 28 | 30.7 mg/L | Standard Deviation 15.7 |
| Placebo | Concentrations of REGN14256 in Serum Over Time (Phase 1) | Day 2 | 37.5 mg/L | Standard Deviation 25.4 |
| Placebo | Concentrations of REGN14256 in Serum Over Time (Phase 1) | Day 59 | 13.5 mg/L | Standard Deviation 7.57 |
| Placebo | Concentrations of REGN14256 in Serum Over Time (Phase 1) | Day 1 | 21.5 mg/L | Standard Deviation 16.6 |
| Placebo | Concentrations of REGN14256 in Serum Over Time (Phase 1) | Day 89 | 7.30 mg/L | Standard Deviation 4.46 |
| Placebo | Concentrations of REGN14256 in Serum Over Time (Phase 1) | Day 6 | 53.2 mg/L | Standard Deviation 29.9 |
| Placebo | Concentrations of REGN14256 in Serum Over Time (Phase 1) | Day 119 | 3.44 mg/L | Standard Deviation 2.42 |
| Placebo | Concentrations of REGN14256 in Serum Over Time (Phase 1) | Pre-dose | 0 mg/L | Standard Deviation 0 |
| Imdevimab (600 mg SC) | Concentrations of REGN14256 in Serum Over Time (Phase 1) | Day 119 | 4.23 mg/L | Standard Deviation 1.73 |
| Imdevimab (600 mg SC) | Concentrations of REGN14256 in Serum Over Time (Phase 1) | Pre-dose | 0 mg/L | Standard Deviation 0 |
| Imdevimab (600 mg SC) | Concentrations of REGN14256 in Serum Over Time (Phase 1) | Post-dose | 9.66 mg/L | Standard Deviation 10.6 |
| Imdevimab (600 mg SC) | Concentrations of REGN14256 in Serum Over Time (Phase 1) | Day 1 | 52.4 mg/L | Standard Deviation 43.3 |
| Imdevimab (600 mg SC) | Concentrations of REGN14256 in Serum Over Time (Phase 1) | Day 2 | 58.5 mg/L | Standard Deviation 38.3 |
| Imdevimab (600 mg SC) | Concentrations of REGN14256 in Serum Over Time (Phase 1) | Day 6 | 63.6 mg/L | Standard Deviation 26.2 |
| Imdevimab (600 mg SC) | Concentrations of REGN14256 in Serum Over Time (Phase 1) | Day 28 | 39.9 mg/L | Standard Deviation 14.6 |
| Imdevimab (600 mg SC) | Concentrations of REGN14256 in Serum Over Time (Phase 1) | Day 59 | 19.6 mg/L | Standard Deviation 5.78 |
| Imdevimab (600 mg SC) | Concentrations of REGN14256 in Serum Over Time (Phase 1) | Day 89 | 9.03 mg/L | Standard Deviation 3.43 |
Secondary
Incidence and Titer of ADA to Imdevimab Over Time
Phase 1, Phase 2, and Phase 3
Time frame: Through Day 169
Population: As prespecified within the SAP (statistical analysis plan), ADA sample analysis was not performed due to early study termination; therefore, ADA analysis data was not generated. No data collected.
Secondary
Incidence and Titer of Anti-drug Antibodies (ADA) to REGN14256 Over Time
Phase 1, Phase 2, and Phase 3
Time frame: Through Day 169
Population: As prespecified within the SAP (statistical analysis plan), ADA sample analysis was not performed due to early study termination; therefore, ADA analysis data was not generated. No data collected.
Secondary
Percentage of Participants With Hypersensitivity Reactions
Phase 2 and Phase 3
Time frame: Through Day 169
Population: The Safety Analysis Set (SAF) includes all randomized participants who received any study drug; it is based on the treatment received. The study was terminated, and Phase 2 and Phase 3 portions of the study were never opened. No data collected.
Secondary
Percentage of Participants With ISRs (Injection-Site Reactions)
Phase 2 and Phase 3
Time frame: Through Day 169
Population: The Safety Analysis Set (SAF) includes all randomized participants who received any study drug; it is based on the treatment received. The study was terminated, and Phase 2 and Phase 3 portions of the study were never opened. No data collected.
Secondary
Percentage of Participants With Treatment-emergent SAEs (Serious Adverse Events)
Phase 2 and Phase 3
Time frame: Through Day 169
Population: The study was terminated, and Phase 2 and Phase 3 portions of the study were never opened
Secondary
Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs)
Phase 1
Time frame: Through Day 169
Population: The Safety Analysis Set (SAF) includes all randomized participants who received any study drug; it is based on the treatment received. The study was terminated, and Phase 2 and Phase 3 portions of the study were never opened.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) | 33.3 Percentage |
| Imdevimab (600 mg SC) | Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) | 20.0 Percentage |
| REGN14256 (600 mg SC) | Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) | 0 Percentage |
| Casirivimab + Imdevimab (1200 mg SC) | Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) | 0 Percentage |
| REGN14256 + Imdevimab (1200 mg SC) | Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) | 0 Percentage |
Secondary
Percentage of Participants With Viral Loads Below the Limit of Detection
Phase 1, Phase 2, and Phase 3
Time frame: Through Day 169
Population: The study was terminated, and Phase 2 and Phase 3 portions of the study were never opened. No data collected.
Secondary
Severity of Hypersensitivity Reactions Over Time
Phase 2 and Phase 3
Time frame: Through Day 169
Population: The Safety Analysis Set (SAF) includes all randomized participants who received any study drug; it is based on the treatment received. The study was terminated, and Phase 2 and Phase 3 portions of the study were never opened. No data collected.
Secondary
Severity of ISRs (Injection-Site Reactions)
Phase 2 and Phase 3
Time frame: Through Day 169
Population: The Safety Analysis Set (SAF) includes all randomized participants who received any study drug; it is based on the treatment received. The study was terminated, and Phase 2 and Phase 3 portions of the study were never opened. No data collected.
Secondary
Severity of TEAEs (Treatment-Emergent Adverse Event)
Phase 2 and Phase 3
Time frame: Through Day 29
Population: The Safety Analysis Set (SAF) includes all randomized participants who received any study drug; it is based on the treatment received. The study was terminated, and Phase 2 and Phase 3 portions of the study were never opened. No data collected.
Secondary
TEAEs (Treatment-Emergent Adverse Events)
Phase 2 and Phase 3
Time frame: Through Day 29
Population: The Safety Analysis Set (SAF) includes all randomized participants who received any study drug; it is based on the treatment received. The study was terminated, and Phase 2 and Phase 3 portions of the study were never opened. No data collected.
Secondary
Time-weighted Average Change From Baseline in Viral Load
Phase 2 and Phase 3 Time-weighted average (TWA) daily change from baseline in viral load (log10 copies/mL) as measured by SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples.
Time frame: Through Day 169
Population: The study was terminated, and Phase 2 and Phase 3 portions of the study were never opened. No data collected.