COVID-19 Administration of Single-Dose Subcutaneous Anti- Spike(s) SARS-CoV-2 Monoclonal Antibodies Casirivimab and Imdevimab in High-Risk Pediatric Participants Under 12 Years of Age

Study Overview
=================
Brief Summary
-----------------
The primary objective of the study is to characterize the concentrations of casirivimab+imdevimab in serum over time after a single subcutaneous (SC) administration The secondary objectives of the study are: To assess the safety and tolerability of SC or single administration of casirivimab+imdevimab To assess the occurrence of grade ≥3 injection site reactions and grade ≥3 hypersensitivity reactions, in participants treated with SC doses of casirivimab+imdevimab To assess the immunogenicity of casirivimab+imdevimab

Official Title
-----------------
A Phase 2A, Open-Label Study Assessing Pharmacokinetics, Safety, Tolerability, and Immunogenicity of Single-Dose Subcutaneous Anti- Spike(s) SARS-COV-2 Monoclonal Antibodies (Casirivimab and Imdevimab) in High-Risk Pediatric Subjects Under 12 Years of Age

Conditions
-----------------
COVID-19

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Is <12 years of age and ≥3 kg to <40 kg at the time parental/guardian consent is signed Has at least one risk factor for developing severe COVID-19 if they were to become infected, such as: Obesity (BMI [kg/m2] ≥95th percentile for age and sex based on CDC growth charts) Cardiovascular disease Chronic lung disease Type 1 or type 2 diabetes mellitus Chronic kidney disease, including those on dialysis Chronic liver disease Immunocompromised or immunodeficient, based on Investigator's assessment (examples include cancer treatment, bone marrow or organ transplantation, immune deficiencies, HIV infection, sickle cell anemia, thalassemia, and prolonged use of immune-weakening medications) Medical complexities (examples include any underlying genetic condition, neurologic condition, metabolic condition, or congenital heart disease) Any other condition deemed by the Investigator to be a risk factor for severe COVID-19 Key Exclusion Criteria: Has positive diagnostic test for SARS-CoV-2 infection from a sample collected during screening ≤7 days prior to study drug administration Note: The sample for the test should be collected ≤7 days within study drug administration, and the result should be reviewed and confirmed negative prior to dosing. Historical records will not be accepted. Has active respiratory or non-respiratory symptoms consistent with COVID-19 in the opinion of the Investigator Has subject-reported clinical history of COVID-19, as determined by Investigator, within the last 90 days Has subject-reported history of prior Emergency Use Authorization (EUA)/approved positive diagnostic test for SARSCoV-2 infection within the last 90 days Is currently hospitalized or was hospitalized for >24 hours for any reason within 14 days of the screening visit Prior use (within 90 days prior to study drug administration) or current use of any investigational, authorized, or approved passive antibody for prophylaxis of SARS-CoV-2 infection, including convalescent plasma, convalescent sera, hyperimmune globulin, or other monoclonal antibodies (eg, bamlanivimab and etesevimab, sotrovimab) Has initiated vaccination for SARS-CoV-2 with an investigational or approved vaccine, but has not completed the vaccine schedule as recommended by the vaccine manufacturer. Plans to receive an investigational or approved SARS-CoV-2 vaccine within 90 days after study drug administration, or per the recommended time frame from the current Centers for Disease Control vaccination guidelines (CDC, 2021b) NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply

Ages Eligible for Study
-----------------
Minimum Age: 1 Minute
Maximum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ≥20 kg to <40 kg<br>SC administration | Drug: casirivimab+imdevimab<br>* Single dose administered based on weight<br>* Other names: RONAPREVE™;|
| Experimental: ≥10 kg to <20 kg<br>SC administration | Drug: casirivimab+imdevimab<br>* Single dose administered based on weight<br>* Other names: RONAPREVE™;|
| Experimental: ≥5 kg to <10 kg<br>SC administration | Drug: casirivimab+imdevimab<br>* Single dose administered based on weight<br>* Other names: RONAPREVE™;|
| Experimental: ≥3 kg to <5 kg<br>SC administration | Drug: casirivimab+imdevimab<br>* Single dose administered based on weight<br>* Other names: RONAPREVE™;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of Casirivimab+Imdevimab in Serum Over Time. | Concentrations reported in milligrams per Liter (mg/L) | Day 0 and Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |  | Through end of study, approximately 24 weeks | 
| Number of Participants With Indicated Severity of TEAEs | Treatment-emergent adverse events (TEAEs) are defined as those that are not present at baseline or represent the exacerbation of a pre-existing condition during the on-treatment period. The severity of AEs were graded using version 5.0 of NCI-CTCAE. | Through end of study, approximately 24 weeks | 
| Number of Participants With Grade ≥3 Injection Site Reactions |  | Through Day 4 | 
| Number of Participants With Grade ≥3 Hypersensitivity Reactions |  | Through Day 4 | 
| Number of Participants With Indicated Immunogenicity as Measured by Anti-drug Antibodies (ADA) to Casirivimab Over Time |  | Up to 24 weeks | 
| Number of Participants With Indicated Immunogenicity as Measured by ADA to Imdevimab Over Time |  | Up to 24 weeks | 
| Immunogenicity as Measured by Neutralizing Antibodies (NAb) to Casirivimab Over Time |  | Up to 24 weeks | 
| Immunogenicity as Measured by NAb to Imdevimab Over Time |  | Up to 24 weeks | 

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