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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
25
Regeneron Research Site
La Mesa, California, United States
Ark Clinical Research
Long Beach, California, United States
PNS Clinical Research, LLC
Mission Viejo, California, United States
Regeneron Research Site
Ft. Pierce, Florida, United States
AGA Clinical Trials
Hialeah, Florida, United States
Treatment Emergent Adverse Events (TEAEs)
Phase 1
Time frame: Through Day 29
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
Percentage of Participants With Injection-site Reactions (ISRs)
Phase 1 only
Time frame: Through Day 169
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
Percentage of Participants With Hypersensitivity Reactions
Phase 1
Time frame: Through Day 169
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
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
Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs)
Phase 1
Time frame: Through Day 169
TEAEs (Treatment-Emergent Adverse Events)
Phase 2 and Phase 3
Time frame: Through Day 29
Severity of TEAEs (Treatment-Emergent Adverse Event)
Phase 2 and Phase 3
Time frame: Through Day 29
Percentage of Participants With ISRs (Injection-Site Reactions)
Phase 2 and Phase 3
Time frame: Through Day 169
Severity of ISRs (Injection-Site Reactions)
Phase 2 and Phase 3
Time frame: Through Day 169
Percentage of Participants With Hypersensitivity Reactions
Phase 2 and Phase 3
Time frame: Through Day 169
Severity of Hypersensitivity Reactions Over Time
Phase 2 and Phase 3
Time frame: Through Day 169
Percentage of Participants With Treatment-emergent SAEs (Serious Adverse Events)
Phase 2 and Phase 3
Time frame: Through Day 169
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
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Regeneron Research Site
Loxahatchee Groves, Florida, United States
Project 4 Research, Inc.
Miami, Florida, United States
Universal Medical and Research Center, LLC
Miami, Florida, United States
Global Medical Trials
Miami, Florida, United States
Bio-Medical Research LLC
Miami, Florida, United States
...and 18 more locations
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
Change From Baseline in Viral Load
Phase 2, and Phase 3 As measured by RT-qPCR in NP samples
Time frame: Through Day 7
Percentage of Participants With Viral Loads Below the Limit of Detection
Phase 1, Phase 2, and Phase 3
Time frame: Through Day 169
Concentrations of REGN14256 in Serum Over Time (Phase 1)
Phase 1
Time frame: Through Day 169
Concentrations of REGN14256 in Serum Over Time
Phase 2 and Phase 3
Time frame: Through Day 169
Concentrations of Imdevimab in Serum Over Time (Phase 1)
Phase 1
Time frame: Through Day 169
Concentrations of Imdevimab in Serum Over Time
Phase 2 and Phase 3
Time frame: Through Day 169
Incidence and Titer of Anti-drug Antibodies (ADA) to REGN14256 Over Time
Phase 1, Phase 2, and Phase 3
Time frame: Through Day 169
Incidence and Titer of ADA to Imdevimab Over Time
Phase 1, Phase 2, and Phase 3
Time frame: Through Day 169