A Study to Evaluate Efficacy and Safety of Casirivimab+Imdevimab (Monoclonal Antibodies) for Prevention of COVID-19 in Immunocompromised Adolescents and Adults

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Immunocompromised

Intervention / Treatment
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* Drug: casirivimab+imdevimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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 Have been fully vaccinated against COVID-19 or deemed medically ineligible to receive full course of vaccine 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 Tested negative for the COVID-19 virus within 72 hours prior to randomization Key Exclusion Criteria: Weighs <40 kg (only applies to participants ≥12 to <18 years of age) Has any signs or symptoms consistent with COVID-19 Past COVID-19 infection within 90 days prior to randomization Planned use of any investigational, authorized, or approved vaccine for COVID-19 within 90 days of the last dose of study drug Prior, current, or planned use of any of COVID-19 convalescent plasma, other monoclonal antibodies against SARS-CoV-2 or any COVID-19 treatment 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 Has any known active acute respiratory infection Has persistent (refractory to treatment for ≥14 days) bacterial or fungal infection Has known allergy or hypersensitivity to components of the study drugs NOTE: Other Protocol Defined Inclusion/Exclusion Criteria Apply

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: casirivimab+imdevimab Initial + Q4W<br>Initial subcutaneous (SC) dose, then SC dose every 4 weeks (Q4W) | Drug: casirivimab+imdevimab<br>* Co-administered sequentially subcutaneous (SC)<br>* Other names: Ronapreve™;|
| Experimental: casirivimab+imdevimab Q4W<br>SC dose Q4W | Drug: casirivimab+imdevimab<br>* Co-administered sequentially subcutaneous (SC)<br>* Other names: Ronapreve™;|
| Experimental: casirivimab+imdevimab Q12W<br>SC dose every 12 weeks (Q12W) | Drug: casirivimab+imdevimab<br>* Co-administered sequentially subcutaneous (SC)<br>* Other names: Ronapreve™;|
| Placebo Comparator: Placebo<br>SC dose Q4W | Drug: Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Incidence of Symptomatic (Broad Term), RT-PCR-confirmed SARS-CoV-2 Infection Cases During the EAP | Cumulative incidence of symptomatic (broad term), RT-PCR-confirmed SARS-CoV-2 infection cases during the Efficacy Assessment Period (EAP) | The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Grade ≥3 Treatment-emergent Adverse Events (TEAEs) During the EAP |  | The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days | 
| Number of Participants With Grade ≥3 Treatment-emergent Adverse Events (TEAEs) During the Follow-Up Period |  | End of EAP to the end of the Follow-Up Period (Day 169 to 205, approximately  1 months) | 
| Number of Participants With TEAEs Leading to Study Drug Discontinuation During the EAP |  | The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days | 
| Number of Participants With TEAEs Leading to Study Drug Discontinuation During the Follow-Up Period |  | End of EAP to the end of the Follow-Up Period (Day 169 to 205, approximately  1 months) | 
| Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the EAP |  | The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days | 
| Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the Follow-Up Period |  | End of EAP to the end of the Follow-Up Period (Day 169 to 205, approximately  1 months) | 
| Incidence of Adverse Events of Special Interest (AESIs) During the EAP |  | The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days | 
| Concentration of Casirivimab Over Time |  | Up to 28 days postdose for the Q4W groups and 84 days postdose for the Q12 group | 
| Concentration of Imdevimab Over Time |  | Up to 28 days postdose for the Q4W groups and 84 days postdose for the Q12 group | 
| Incidence of Anti-drug Antibodies (ADA) Over Time |  | Up to 28 days postdose for the Q4W groups and 84 days postdose for the Q12 group | 
| Incidence of Neutralizing Antibodies (NAb) to Each mAb Over Time |  | Up to 28 days postdose for the Q4W groups and 84 days postdose for the Q12 group | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-response to COVID-19 vaccination, COVID-19, Immunocompromised, weakened immune system