Clinical trial NCT05081388: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: SARS-CoV-2
Keywords: COVID-19
Non-hospitalized
Low-risk
Symptomatic
Coronavirus disease 2019 (COVID-19)
Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2)
coronavirus
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-10-18
Enrollment: 25
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase1/Phase2/Phase3
Primary purpose: TREATMENT

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


Eligibility 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 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

Primary outcomes:
measure: Treatment Emergent Adverse Events (TEAEs)
timeFrame: Through Day 29
measure: Severity of TEAEs
timeFrame: Through Day 29
measure: Percentage of Participants With Injection-site Reactions (ISRs)
timeFrame: Through Day 169
measure: Severity of ISRs (Injection Site Reactions)
timeFrame: Through Day 29
measure: Percentage of Participants With Hypersensitivity Reactions
timeFrame: Through Day 169
measure: Severity of Hypersensitivity Reactions Over Time
timeFrame: Through Day 169
measure: Time-weighted Average (TWA) Daily Change From Baseline in Viral Load (log10 Copies/mL)
timeFrame: Day 1 to day 7
Secondary outcomes:
measure: Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs)
timeFrame: Through Day 169
measure: TEAEs (Treatment-Emergent Adverse Events)
timeFrame: Through Day 29
measure: Severity of TEAEs (Treatment-Emergent Adverse Event)
timeFrame: Through Day 29
measure: Percentage of Participants With ISRs (Injection-Site Reactions)
timeFrame: Through Day 169
measure: Severity of ISRs (Injection-Site Reactions)
timeFrame: Through Day 169
measure: Percentage of Participants With Hypersensitivity Reactions
timeFrame: Through Day 169
measure: Severity of Hypersensitivity Reactions Over Time
timeFrame: Through Day 169
measure: Percentage of Participants With Treatment-emergent SAEs (Serious Adverse Events)
timeFrame: Through Day 169
measure: Time-weighted Average Change From Baseline in Viral Load
timeFrame: Through Day 169
measure: Change From Baseline in Viral Load (Phase 1)
timeFrame: Through Day 7
measure: Change From Baseline in Viral Load
timeFrame: Through Day 7
measure: Percentage of Participants With Viral Loads Below the Limit of Detection
timeFrame: Through Day 169
measure: Concentrations of REGN14256 in Serum Over Time (Phase 1)
timeFrame: Through Day 169
measure: Concentrations of REGN14256 in Serum Over Time
timeFrame: Through Day 169
measure: Concentrations of Imdevimab in Serum Over Time (Phase 1)
timeFrame: Through Day 169
measure: Concentrations of Imdevimab in Serum Over Time
timeFrame: Through Day 169
measure: Incidence and Titer of Anti-drug Antibodies (ADA) to REGN14256 Over Time
timeFrame: Through Day 169
measure: Incidence and Titer of ADA to Imdevimab Over Time
timeFrame: Through Day 169
Other outcomes:
Locations:
city: La Mesa
country: United States
facility: Regeneron Research Site
state: California
city: Long Beach
country: United States
facility: Ark Clinical Research
state: California
city: Mission Viejo
country: United States
facility: PNS Clinical Research, LLC
state: California
city: Fort Pierce
country: United States
facility: Regeneron Research Site
state: Florida
city: Hialeah
country: United States
facility: AGA Clinical Trials
state: Florida
city: Loxahatchee Groves
country: United States
facility: Regeneron Research Site
state: Florida
city: Miami Lakes
country: United States
facility: Charisma Research and Medical Center
state: Florida
city: Miami
country: United States
facility: Project 4 Research, Inc.
state: Florida
city: Miami
country: United States
facility: Universal Medical and Research Center, LLC
state: Florida
city: Miami
country: United States
facility: Global Medical Trials
state: Florida
city: Miami
country: United States
facility: Bio-Medical Research LLC
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A.
state: Florida
city: Winter Park
country: United States
facility: Regeneron Research Site
state: Florida
city: Columbus
country: United States
facility: IACT Health
state: Georgia
city: Chicago
country: United States
facility: Chicago Clinical Research Institute
state: Illinois
city: Ames
country: United States
facility: Regeneron Research Site
state: Iowa
city: Marrero
country: United States
facility: Regeneron Research Site
state: Louisiana
city: Olive Branch
country: United States
facility: Olive Branch Family Medical Center
state: Mississippi
city: Las Vegas
country: United States
facility: Forte Family Practice
state: Nevada
city: Bronx
country: United States
facility: New York Health and Hospitals / Lincoln
state: New York
city: Bronx
country: United States
facility: NYC H+H / Jacobi Medical Center
state: New York
city: Wilmington
country: United States
facility: Regeneron Research Site
state: North Carolina
city: Dayton
country: United States
facility: Regeneron Research Site
state: Ohio
city: Clinton
country: United States
facility: Carolina Medical Research
state: South Carolina
city: Amarillo
country: United States
facility: PharmaTex Research, LLC
state: Texas
city: Houston
country: United States
facility: Advanced Diagnostics Clinic, River Oaks Hospital and Clinics
state: Texas
city: Houston
country: United States
facility: Regeneron Research Site
state: Texas
city: Houston
country: United States
facility: Regeneron Research Site
state: Texas
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: