Clinical trial NCT05074433: A Study to Evaluate Efficacy and Safety of Casirivimab+Imdevimab (Monoclonal Antibodies) for Prevention of COVID-19 in Immunocompromised Adolescents and Adults
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Anti-Spike SARS-CoV-2 Monoclonal Antibodies as Pre-Exposure Prophylaxis to Prevent COVID-19 in Immunocompromised Participants
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Immunocompromised
Keywords: Non-response to COVID-19 vaccination
COVID-19
Immunocompromised, weakened immune system
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-10-12
Enrollment: 66
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: The primary objective of the study is to evaluate the effect of casirivimab+imdevimab, compared with placebo, in preventing symptomatic SARS-CoV-2 infection in immunocompromised participants.

The secondary objectives of the study are:

* To evaluate the safety and tolerability of repeated SC injections of casirivimab+imdevimab in the study population
* To characterize concentrations of casirivimab and imdevimab in serum over time
* To assess the immunogenicity of casirivimab and imdevimab


Eligibility criteria: Key Inclusion Criteria:

1. Meets ≥1 of the following criteria:

   * Is immunocompromised, including people with transplant, who have cancer, primary immunodeficiencies, HIV, rheumatological disease, autoimmune disease, multiple sclerosis OR
   * Currently taking immunosuppressant drugs
2. Have been fully vaccinated against COVID-19 or deemed medically ineligible to receive full course of vaccine
3. Has documented negative serology/antibody response in an anti-SARS-CoV-2 spike protein IgG clinical test or ≤50 U/mL on the Elecsys® SARS-CoV-2 S Total Ig test
4. Tested negative for the COVID-19 virus within 72 hours prior to randomization

Key Exclusion Criteria:

1. Weighs \<40 kg (only applies to participants ≥12 to \<18 years of age)
2. Has any signs or symptoms consistent with COVID-19
3. Past COVID-19 infection within 90 days prior to randomization
4. Planned use of any investigational, authorized, or approved vaccine for COVID-19 within 90 days of the last dose of study drug
5. Prior, current, or planned use of any of COVID-19 convalescent plasma, other monoclonal antibodies against SARS-CoV-2 or any COVID-19 treatment
6. Is planned to begin immunoglobulin (IVIG) or immunoglobulin (SCIG) therapy, is planned to have a change to existing IVIG or SCIG, or has been on a chronic stable dose of their IVIG or SCIG regimen for less than 90 days prior to screening
7. Has any known active acute respiratory infection
8. Has persistent (refractory to treatment for ≥14 days) bacterial or fungal infection
9. Has known allergy or hypersensitivity to components of the study drugs

NOTE: Other Protocol Defined Inclusion/Exclusion Criteria Apply

Primary outcomes:
measure: Cumulative Incidence of Symptomatic (Broad Term), RT-PCR-confirmed SARS-CoV-2 Infection Cases During the EAP
timeFrame: The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days
Secondary outcomes:
measure: Number of Participants With Grade ≥3 Treatment-emergent Adverse Events (TEAEs) During the EAP
timeFrame: The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days
measure: Number of Participants With Grade ≥3 Treatment-emergent Adverse Events (TEAEs) During the Follow-Up Period
timeFrame: End of EAP to the end of the Follow-Up Period (Day 169 to 205, approximately ~1 months)
measure: Number of Participants With TEAEs Leading to Study Drug Discontinuation During the EAP
timeFrame: The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days
measure: Number of Participants With TEAEs Leading to Study Drug Discontinuation During the Follow-Up Period
timeFrame: End of EAP to the end of the Follow-Up Period (Day 169 to 205, approximately ~1 months)
measure: Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the EAP
timeFrame: The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days
measure: Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the Follow-Up Period
timeFrame: End of EAP to the end of the Follow-Up Period (Day 169 to 205, approximately ~1 months)
measure: Incidence of Adverse Events of Special Interest (AESIs) During the EAP
timeFrame: The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days
measure: Concentration of Casirivimab Over Time
timeFrame: Up to 28 days postdose for the Q4W groups and 84 days postdose for the Q12 group
measure: Concentration of Imdevimab Over Time
timeFrame: Up to 28 days postdose for the Q4W groups and 84 days postdose for the Q12 group
measure: Incidence of Anti-drug Antibodies (ADA) Over Time
timeFrame: Up to 28 days postdose for the Q4W groups and 84 days postdose for the Q12 group
measure: Incidence of Neutralizing Antibodies (NAb) to Each mAb Over Time
timeFrame: Up to 28 days postdose for the Q4W groups and 84 days postdose for the Q12 group
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Central Alabama Research
state: Alabama
city: Little Rock
country: United States
facility: Baptist Health Center for Clinical Research
state: Arkansas
city: Long Beach
country: United States
facility: Regeneron Study Site
state: California
city: Los Angeles
country: United States
facility: Regeneron Study Site
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Sacramento
country: United States
facility: University of California
state: California
city: Stanford
country: United States
facility: Regeneron Study Site
state: California
city: West Hollywood
country: United States
facility: James R Berenson MD Inc.
state: California
city: Aurora
country: United States
facility: University Of Colorado
state: Colorado
city: North Haven
country: United States
facility: Regeneron Study Site
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Aventura
country: United States
facility: Arthritis and Rheumatic Disease Specialties
state: Florida
city: Clearwater
country: United States
facility: Innovative Research of West Florida, Inc.
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Hollywood
country: United States
facility: Elixia COVID-19
state: Florida
city: Miami
country: United States
facility: AppleMed Research Group, LLC
state: Florida
city: Miami
country: United States
facility: De La Cruz Research Center, LLC
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Zephyrhills
country: United States
facility: Florida Medical Clinic, LLC
state: Florida
city: Atlanta
country: United States
facility: Regeneron Study Site
state: Georgia
city: Marietta
country: United States
facility: Regeneron Study Site
state: Georgia
city: Chicago
country: United States
facility: Great Lakes Clinical Trials - Ravenswood
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Baltimore
country: United States
facility: Institute of Human Virology
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Bethesda
country: United States
facility: Laboratory of Clinical Immunology and Microbiology, NIAID
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Regeneron Study Site
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: Teaneck
country: United States
facility: Holy Name
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Brooklyn
country: United States
facility: Maimonides Cancer Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Regeneron Study Site
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Regeneron Study Site 2
state: New York
city: Rochester
country: United States
facility: Regeneron Study Site
state: New York
city: Syracuse
country: United States
facility: Regeneron Study Site
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Morganton
country: United States
facility: Burke Primary Care
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Cleveland
country: United States
facility: Regeneron Study Site
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Philadelphia
country: United States
facility: Penn Prevention Clinical Research Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Providence
country: United States
facility: Regeneron Study Site
state: Rhode Island
city: Jackson
country: United States
facility: West Tennessee Research Institute
state: Tennessee
city: Amarillo
country: United States
facility: PharmaTex Research, LLC
state: Texas
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, PA
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: Synergy Group Medical,LLC
state: Texas
city: Richmond
country: United States
facility: Regeneron Study Site
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: Regeneron Study Site
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center- First Hill
state: Washington
city: Madison
country: United States
facility: University of Wisconsin - Madison
state: Wisconsin
city: Cuauhtemoc
country: Mexico
facility: Regeneron Study Site
state: Distrito Federal
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: