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

Sponsor

Regeneron Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT05081388

Collaborator

(none)

Enrollment

Locations

Arms

7.7

Actual Duration (Months)

0.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
SARS-CoV-2	Drug: REGN14256 Drug: imdevimab Drug: casirivimab + imdevimab Drug: Placebo	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

25 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Phase1/Phase2/Phase3Phase1/Phase2/Phase3

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 8, 2021

Actual Primary Completion Date :

Jun 30, 2022

Actual Study Completion Date :

Jun 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: REGN14256 + 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)	Drug: REGN14256 Sub-cutaneous (SC) single dose Drug: imdevimab SC single dose Other Names: REGN10987
Experimental: REGN14256 Phase 1, Phase 2: Randomized 1:1:1:1:1	Drug: REGN14256 Sub-cutaneous (SC) single dose
Experimental: Imdevimab Phase 1, Phase 2: Randomized 1:1:1:1:1	Drug: imdevimab SC single dose Other Names: REGN10987
Experimental: casirivimab + imdevimab Phase 1, Phase 2: Randomized 1:1:1:1:1 Phase 3: (≥18 Years): Randomized 1:1:1	Drug: imdevimab SC single dose Other Names: REGN10987 Drug: casirivimab + imdevimab SC single dose Other Names: REGN10933 + REGN10987 REGN-COV2 REGEN-COV™ Ronapreve™
Experimental: Placebo Phase 1, Phase 2: Randomized 1:1:1:1:1 Phase 3: (≥18 Years): Randomized 1:1:1	Drug: Placebo SC single dose

Outcome Measures

Primary Outcome Measures

Treatment emergent adverse events (TEAEs) [Through Day 29]
Phase 1
Severity of TEAEs [Through Day 29]
Phase 1
Proportion of patients with injection-site reactions (ISRs) [Through Day 169]
Phase 1
Severity of ISRs [Through Day 169]
Phase 1
Proportion of patients with hypersensitivity reactions [Through Day 169]
Phase 1
Severity of hypersensitivity reactions over time [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 1/2 Measured by SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples
Time to COVID-19 symptoms resolution [Through Day 169]
Phase 1/2/3

Secondary Outcome Measures

Proportion of patients with treatment-emergent serious adverse events (SAEs) [Through Day 169]
Phase 1
TEAEs [Through Day 29]
Phase 2 and Phase 3
Severity of TEAEs [Through Day 29]
Phase 2 and Phase 3
Proportion of patients with ISRs [Through Day 169]
Phase 2 and Phase 3
Severity of ISRs [Through Day 169]
Phase 2 and Phase 3
Proportion of patients 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
Proportion of patients with treatment-emergent SAEs [Through Day 169]
Phase 2 and Phase 3
Time-weighted average change from baseline in viral load [Through Day 169]
Phase 1, Phase 2, and Phase 3 Measured by RT-qPCR in NP samples
Change from baseline in viral load [Through Day 7]
Phase 1, Phase 2, and Phase 3 As measured by RT-qPCR in NP samples
Proportion of patients 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 [Through Day 169]
Phase 1, Phase 2, and Phase 3
Concentrations of imdevimab in serum over time [Through Day 169]
Phase 1, 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

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

For the adolescent cohort in Phase 3 only: Weighs ≥40 kg at randomization
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
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
Maintains O2 saturation ≥93% on room air

Key Exclusion Criteria:

Has a medical condition or other factors associated with high risk for progression to severe COVID-19:
Cancer
Cardiovascular disease (such as heart failure, coronary artery disease, cardiomyopathies, congenital heart disease or hypertension)
Chronic lung disease including chronic obstructive pulmonary disease, asthma (moderate to severe), interstitial lung disease, cystic fibrosis, and pulmonary hypertension
Chronic kidney disease at any stage
Chronic liver disease (such as alcohol-related, nonalcoholic fatty liver disease, cirrhosis)
Dementia or other chronic neurological condition
Diabetes mellitus (type 1 or type 2)
Immunodeficiency disease or taking immunosuppressive treatment
Medical-related technological dependence [for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19)]
Neurodevelopmental disorder (for example, cerebral palsy) or other condition that confers medical complexity (for example, genetic or metabolic syndromes and severe congenital anomalies)
Overweight (defined as BMI >25 kg/m2) or obesity (defined as BMI ≥30 kg/m2)
Poorly controlled HIV infection or AIDS
Pregnancy
Sickle cell disease or thalassemia
Stroke or cerebrovascular disease
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
Was admitted to a hospital for COVID-19 prior to randomization, or is hospitalized (inpatient) for any reason at randomization
Has a known prior SARS-CoV-2 infection or positive SARS-CoV-2 serologic test
Has a positive SARS-CoV-2 antigen or molecular diagnostic test from a sample collected

72 hours prior to randomization

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
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)
Has known active infection with influenza or other non-SARS-CoV-2 respiratory pathogen, confirmed by a diagnostic test
Has been discharged, or is planned to be discharged, to a quarantine center
Has participated, is participating, or plans to participate in a clinical research study evaluating any authorized, approved, or investigational vaccine for COVID-19
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Regeneron Research Site	La Mesa	California	United States	91941
2	Ark Clinical Research	Long Beach	California	United States	90806
3	PNS Clinical Research, LLC	Mission Viejo	California	United States	92691
4	Regeneron Research Site	Fort Pierce	Florida	United States	34982
5	AGA Clinical Trials	Hialeah	Florida	United States	33012
6	Regeneron Research Site	Loxahatchee Groves	Florida	United States	33470
7	Charisma Research and Medical Center	Miami Lakes	Florida	United States	33014
8	Project 4 Research, Inc.	Miami	Florida	United States	33125
9	Universal Medical and Research Center, LLC	Miami	Florida	United States	33126
10	Global Medical Trials	Miami	Florida	United States	33174
11	Bio-Medical Research LLC	Miami	Florida	United States	33184
12	Triple O Research Institute, P.A.	West Palm Beach	Florida	United States	33407
13	Regeneron Research Site	Winter Park	Florida	United States	32789
14	IACT Health	Columbus	Georgia	United States	31904
15	Chicago Clinical Research Institute	Chicago	Illinois	United States	60607
16	Regeneron Research Site	Ames	Iowa	United States	50010
17	Regeneron Research Site	Marrero	Louisiana	United States	70072
18	Olive Branch Family Medical Center	Olive Branch	Mississippi	United States	38654
19	Forte Family Practice	Las Vegas	Nevada	United States	89103
20	New York Health and Hospitals / Lincoln	Bronx	New York	United States	10451
21	NYC H+H / Jacobi Medical Center	Bronx	New York	United States	10461
22	Regeneron Research Site	Wilmington	North Carolina	United States	28401
23	Regeneron Research Site	Dayton	Ohio	United States	45409
24	Carolina Medical Research	Clinton	South Carolina	United States	29325
25	PharmaTex Research, LLC	Amarillo	Texas	United States	79109
26	Advanced Diagnostics Clinic, River Oaks Hospital and Clinics	Houston	Texas	United States	77027
27	Regeneron Research Site	Houston	Texas	United States	77030
28	Regeneron Research Site	Houston	Texas	United States	77093