COVID-19 Study to Evaluate Safety, Tolerability, and Efficacy of REGN14256+Imdevimab for the Treatment of COVID-19 Adult and Adolescent Patients Without Risk Factors for Progression to Severe Disease

Phase 1

Terminated

• Conditions: SARS-CoV-2
• Interventions: Drug: imdevimab; Drug: REGN14256; Drug: Placebo; Drug: casirivimab + imdevimab

• Registration Number: NCT05081388
• Lead Sponsor: Regeneron Pharmaceuticals

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-10-14
• Study First Submitted QC: 2021-10-14
• Study First Posted: 2021-10-18
• Study Start: 2021-11-08
• Primary Completion: 2022-06-30
• Study Completion: 2022-06-30
• Results First Submitted: 2023-06-29
• Status Verified: 2023-11
• Results First Submitted QC: 2023-11-15
• Last Update Submitted: 2023-11-15
• Results First Posted: 2024-04-26
• Last Update Posted: 2024-04-26

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 25

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

Exclusion Criteria

1. Has a medical condition or other factors associated with high risk for progression to severe COVID-19:

   1. Cancer
   2. Cardiovascular disease (such as heart failure, coronary artery disease, cardiomyopathies, congenital heart disease or hypertension)
   3. Chronic lung disease including chronic obstructive pulmonary disease, asthma (moderate to severe), interstitial lung disease, cystic fibrosis, and pulmonary hypertension
   4. Chronic kidney disease at any stage
   5. Chronic liver disease (such as alcohol-related, nonalcoholic fatty liver disease, cirrhosis)
   6. Dementia or other chronic neurological condition
   7. Diabetes mellitus (type 1 or type 2)
   8. Immunodeficiency disease or taking immunosuppressive treatment
   9. Medical-related technological dependence [for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19)]
   10. Neurodevelopmental disorder (for example, cerebral palsy) or other condition that confers medical complexity (for example, genetic or metabolic syndromes and severe congenital anomalies)
   11. Overweight (defined as BMI >25 kg/m2) or obesity (defined as BMI ≥30 kg/m2)
   12. Poorly controlled HIV infection or AIDS
   13. Pregnancy
   14. Sickle cell disease or thalassemia
   15. Stroke or cerebrovascular disease

2. Prior, current (at randomization) or planned use (within time period given per CDC guidance [90 days]) of any authorized or approved vaccine for COVID-19

3. Was admitted to a hospital for COVID-19 prior to randomization, or is hospitalized (inpatient) for any reason at randomization

4. Has a known prior SARS-CoV-2 infection or positive SARS-CoV-2 serologic test

5. Has a positive SARS-CoV-2 antigen or molecular diagnostic test from a sample collected >72 hours prior to randomization

6. Has participated, or is participating, in a clinical research study evaluating COVID-19 convalescent plasma, mAbs against SARS-CoV-2, or intravenous immunoglobulin (IVIG) within 3 months or within 5 half-lives of the investigational product (whichever is longer) prior to the screening visit

7. Prior, current, or any of the following treatments: COVID-19 convalescent plasma, mAbs against SARS-CoV-2, IVIG (any indication), systemic corticosteroids (any indication), or COVID-19 treatments (authorized, approved, or investigational)

8. Has known active infection with influenza or other non-SARS-CoV-2 respiratory pathogen, confirmed by a diagnostic test

9. Has been discharged, or is planned to be discharged, to a quarantine center

10. Has participated, is participating, or plans to participate in a clinical research study evaluating any authorized, approved, or investigational vaccine for COVID-19

11. For Phase 1only: Women of childbearing potential (WOCBP) who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment and for at least 6 months after study drug administration as described in the protocol

Note: Other protocol-defined inclusion/ exclusion criteria apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
casirivimab + imdevimab	imdevimab	Phase 1, Phase 2: Randomized 1:1:1:1:1 Phase 3: (≥18 Years): Randomized 1:1:1
REGN14256 + imdevimab	REGN14256	Phase 1, Phase 2: Randomized 1:1:1:1:1 Phase 3: (≥18 Years): Randomized 1:1:1 Phase 3: (Open label) (≥12 and \<18 Years)
REGN14256 + imdevimab	imdevimab	Phase 1, Phase 2: Randomized 1:1:1:1:1 Phase 3: (≥18 Years): Randomized 1:1:1 Phase 3: (Open label) (≥12 and \<18 Years)
REGN14256	REGN14256	Phase 1, Phase 2: Randomized 1:1:1:1:1
Imdevimab	imdevimab	Phase 1, Phase 2: Randomized 1:1:1:1:1
casirivimab + imdevimab	casirivimab + imdevimab	Phase 1, Phase 2: Randomized 1:1:1:1:1 Phase 3: (≥18 Years): Randomized 1:1:1
Placebo	Placebo	Phase 1, Phase 2: Randomized 1:1:1:1:1 Phase 3: (≥18 Years): Randomized 1:1:1

Primary Outcome Measures

Name	Time	Method
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
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
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
Treatment Emergent Adverse Events (TEAEs)	Through Day 29	Phase 1
Percentage of Participants With Hypersensitivity Reactions	Through Day 169	Phase 1
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 Outcome Measures

Name	Time	Method
Severity of ISRs (Injection-Site Reactions)	Through Day 169	Phase 2 and Phase 3
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
Concentrations of REGN14256 in Serum Over Time	Through Day 169	Phase 2 and Phase 3
Incidence and Titer of ADA to Imdevimab Over Time	Through Day 169	Phase 1, Phase 2, and Phase 3
TEAEs (Treatment-Emergent Adverse Events)	Through Day 29	Phase 2 and Phase 3
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
Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs)	Through Day 169	Phase 1
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
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
Percentage of Participants With Treatment-emergent SAEs (Serious Adverse Events)	Through Day 169	Phase 2 and Phase 3
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.
Percentage of Participants With Viral Loads Below the Limit of Detection	Through Day 169	Phase 1, Phase 2, and Phase 3
Concentrations of REGN14256 in Serum Over Time (Phase 1)	Through Day 169	Phase 1
Concentrations of Imdevimab in Serum Over Time (Phase 1)	Through Day 169	Phase 1

Trial Locations

Locations (19)

PNS Clinical Research, LLC; 🇺🇸 Mission Viejo, California, United States

PharmaTex Research, LLC; 🇺🇸 Amarillo, Texas, United States

Ark Clinical Research; 🇺🇸 Long Beach, California, United States

IACT Health; 🇺🇸 Columbus, Georgia, United States

Carolina Medical Research; 🇺🇸 Clinton, South Carolina, United States

Triple O Research Institute, P.A.; 🇺🇸 West Palm Beach, Florida, United States

Chicago Clinical Research Institute; 🇺🇸 Chicago, Illinois, United States

Charisma Research and Medical Center; 🇺🇸 Miami Lakes, Florida, United States

Regeneron Research Site; 🇺🇸 Houston, Texas, United States

Project 4 Research, Inc.; 🇺🇸 Miami, Florida, United States

Universal Medical and Research Center, LLC; 🇺🇸 Miami, Florida, United States

Forte Family Practice; 🇺🇸 Las Vegas, Nevada, United States

Bio-Medical Research LLC; 🇺🇸 Miami, Florida, United States

AGA Clinical Trials; 🇺🇸 Hialeah, Florida, United States

Olive Branch Family Medical Center; 🇺🇸 Olive Branch, Mississippi, United States

Global Medical Trials; 🇺🇸 Miami, Florida, United States

Advanced Diagnostics Clinic, River Oaks Hospital and Clinics; 🇺🇸 Houston, Texas, United States

New York Health and Hospitals / Lincoln; 🇺🇸 Bronx, New York, United States

NYC H+H / Jacobi Medical Center; 🇺🇸 Bronx, New York, United States