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

SARS-CoV-2 Clinical Trial

Official title:

A Phase 1/2/3 Adaptive Study to Evaluate the Safety, Tolerability, and Efficacy of REGN14256+Imdevimab for the Treatment of COVID-19 Patients Without Risk Factors for Progression to Severe Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05081388
• Other study ID #: R14256-COV-2149
• Status: Terminated
• Phase: Phase 1
• Start date: November 8, 2021
• Est. completion date: June 30, 2022

Study information

• Verified date: November 2023
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

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 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

Related Conditions & MeSH terms

• COVID-19
• SARS-CoV-2

Intervention

Drug:
• REGN14256
Sub-cutaneous (SC) single dose
• imdevimab
SC single dose
• casirivimab + imdevimab
SC single dose
• Placebo
SC single dose

Locations

Country	Name	City	State
United States	PharmaTex Research, LLC	Amarillo	Texas
United States	Regeneron Research Site	Ames	Iowa
United States	New York Health and Hospitals / Lincoln	Bronx	New York
United States	NYC H+H / Jacobi Medical Center	Bronx	New York
United States	Chicago Clinical Research Institute	Chicago	Illinois
United States	Carolina Medical Research	Clinton	South Carolina
United States	IACT Health	Columbus	Georgia
United States	Regeneron Research Site	Dayton	Ohio
United States	Regeneron Research Site	Fort Pierce	Florida
United States	AGA Clinical Trials	Hialeah	Florida
United States	Advanced Diagnostics Clinic, River Oaks Hospital and Clinics	Houston	Texas
United States	Regeneron Research Site	Houston	Texas
United States	Regeneron Research Site	Houston	Texas
United States	Regeneron Research Site	La Mesa	California
United States	Forte Family Practice	Las Vegas	Nevada
United States	Ark Clinical Research	Long Beach	California
United States	Regeneron Research Site	Loxahatchee Groves	Florida
United States	Regeneron Research Site	Marrero	Louisiana
United States	Bio-Medical Research LLC	Miami	Florida
United States	Global Medical Trials	Miami	Florida
United States	Project 4 Research, Inc.	Miami	Florida
United States	Universal Medical and Research Center, LLC	Miami	Florida
United States	Charisma Research and Medical Center	Miami Lakes	Florida
United States	PNS Clinical Research, LLC	Mission Viejo	California
United States	Olive Branch Family Medical Center	Olive Branch	Mississippi
United States	Triple O Research Institute, P.A.	West Palm Beach	Florida
United States	Regeneron Research Site	Wilmington	North Carolina
United States	Regeneron Research Site	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment Emergent Adverse Events (TEAEs)	Phase 1	Through Day 29
Primary	Severity of TEAEs	Severity was based on Grading. Grade 1 was less severe. Grade 5 was more severe.; - Mild; Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; - Moderate; Minimal, local, or noninvasive intervention indicated; limiting age appropriate instrumental activities of daily living (ADL); - Severe; Severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; ADL2 limiting self-care; - Life-threatening; Life threatening consequences; urgent intervention indicated; - Death; Death related to adverse events	Through Day 29
Primary	Percentage of Participants With Injection-site Reactions (ISRs)	Phase 1 only	Through Day 169
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	Through Day 29
Primary	Percentage of Participants With Hypersensitivity Reactions	Phase 1	Through Day 169
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	Through Day 169
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	Day 1 to day 7
Secondary	Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs)	Phase 1	Through Day 169
Secondary	TEAEs (Treatment-Emergent Adverse Events)	Phase 2 and Phase 3	Through Day 29
Secondary	Severity of TEAEs (Treatment-Emergent Adverse Event)	Phase 2 and Phase 3	Through Day 29
Secondary	Percentage of Participants With ISRs (Injection-Site Reactions)	Phase 2 and Phase 3	Through Day 169
Secondary	Severity of ISRs (Injection-Site Reactions)	Phase 2 and Phase 3	Through Day 169
Secondary	Percentage of Participants With Hypersensitivity Reactions	Phase 2 and Phase 3	Through Day 169
Secondary	Severity of Hypersensitivity Reactions Over Time	Phase 2 and Phase 3	Through Day 169
Secondary	Percentage of Participants With Treatment-emergent SAEs (Serious Adverse Events)	Phase 2 and Phase 3	Through Day 169
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.	Through Day 169
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.	Through Day 7
Secondary	Change From Baseline in Viral Load	Phase 2, and Phase 3 As measured by RT-qPCR in NP samples	Through Day 7
Secondary	Percentage of Participants With Viral Loads Below the Limit of Detection	Phase 1, Phase 2, and Phase 3	Through Day 169
Secondary	Concentrations of REGN14256 in Serum Over Time (Phase 1)	Phase 1	Through Day 169
Secondary	Concentrations of REGN14256 in Serum Over Time	Phase 2 and Phase 3	Through Day 169
Secondary	Concentrations of Imdevimab in Serum Over Time (Phase 1)	Phase 1	Through Day 169
Secondary	Concentrations of Imdevimab in Serum Over Time	Phase 2 and Phase 3	Through Day 169
Secondary	Incidence and Titer of Anti-drug Antibodies (ADA) to REGN14256 Over Time	Phase 1, Phase 2, and Phase 3	Through Day 169
Secondary	Incidence and Titer of ADA to Imdevimab Over Time	Phase 1, Phase 2, and Phase 3	Through Day 169