COVID-19 Study Assessing the Safety and Tolerability of Co-Formulated Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies (Casirivimab+Imdevimab) in Adult Volunteers

Study Overview
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Brief Summary
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The primary objective of the study is to assess the safety and tolerability of co-formulated subcutaneous (SC) and intravenous (IV) casirivimab+imdevimab The secondary objectives of the study are to: Explore variability in the drug concentration profiles of casirivimab and imdevimab after co-formulated subcutaneous (SC) or intravenous (IV) administration Characterize the immunogenicity of casirivimab and imdevimab in serum over time

Official Title
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A Phase 1, Randomized, Open-Label Study Assessing the Safety and Tolerability of Co-Formulated Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies (Casirivimab+Imdevimab) in Adult Volunteers

Conditions
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Healthy, Chronic Stable Illness

Intervention / Treatment
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* Drug: Casirivimab+Imdevimab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Is healthy, or has chronic medical condition(s) that per the opinion of the investigator is (are) stable, well-controlled, and not likely to require medical intervention through the end of study Does not require medication(s) for co-morbid condition, or has received stable medication(s) for co-morbid condition(s) for at least 6 months prior to screening Weighs between ≥60 kg and ≤100 kg at the time of screening Has SARS-CoV-2-negative reverse-transcriptase polymerase chain reaction (RT-PCR) from a sample collected ≤72 hours prior to randomization, using local assay and sample collection and assay standards Has completed a full course of COVID-19 vaccination more than 6 weeks prior to randomization Key Exclusion Criteria: Has active respiratory or non-respiratory symptoms consistent with COVID-19 in the opinion of the Investigator Has recent SARS-CoV-2 infection that resolved within 6 weeks prior to randomization Prior use of casirivimab+imdevimab at any time prior to randomization Prior, current, or planned use during the study of any of the following treatments: COVID-19 convalescent plasma, other monoclonal antibodies against SARS-CoV-2 (eg, bamlanivimab and etesevimab, sotrovimab), intravenous immunoglobulin (any indication), or any other investigational, authorized, or approved agent intended for COVID-19 treatment or prevention (with the exception of COVID-19 vaccines) Treatment with another investigational drug in the last 30 days or within 5 half-lives of the investigational drug, whichever is longer, prior to screening Body mass index (BMI) ≥28 kg/m2 Medically-attended acute illness, systemic antibiotics use, or hospitalization for any reason within 30 days prior to screening Acute exacerbation of a chronic pulmonary condition (eg, chronic obstructive pulmonary disease [COPD], asthma exacerbations) in the past 6 months prior to screening Uncontrolled hypertension, in the opinion of the investigator History of heart failure hospitalization, diagnosis of a myocardial infarction, stroke, transient ischemic attack, unstable angina, percutaneous or surgical revascularization procedure (coronary, carotid, or peripheral vascular), or intracardiac device placement (eg, pacemaker) within 12 months prior to screening Cancer requiring treatment currently or in the past 5 years, except for non-melanoma skin cancer or cervical/anus in-situ Is pregnant at screening Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Co-formulated casirivimab+imdevimab SC<br>Randomized 1:1 | Drug: Casirivimab+Imdevimab<br>* Randomized 1:1 for intravenous (IV) or subcutaneous (SC) administration<br>* Other names: Ronapreve™;|
| Experimental: Co-formulated casirivimab+imdevimab IV<br>Randomized 1:1 | Drug: Casirivimab+Imdevimab<br>* Randomized 1:1 for intravenous (IV) or subcutaneous (SC) administration<br>* Other names: Ronapreve™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Targeted grade ≥3 treatment-emergent adverse events (TEAEs) |  | Through end of study, approximately 16 weeks | 
| Grade ≥3 injection-site reactions (ISRs) |  | Through end of study, approximately 16 weeks | 
| Grade ≥2 infusion-related reactions (IRRs) |  | Through end of study, approximately 16 weeks | 
| Grade ≥2 hypersensitivity reactions |  | Through end of study, approximately 16 weeks | 
| Serious adverse events (SAEs) |  | Through end of study, approximately 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of casirivimab and imdevimab in serum over time |  | Up to 16 weeks | 
| Incidence and titer of anti-drug antibodies (ADA) to casirivimab and imdevimab |  | Up to 16 weeks | 
| Incidence of neutralizing antibodies (NAb) to casirivimab and imdevimab |  | Up to 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2)