COVID-19
Conditions
Keywords
Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), coronavirus
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
Interventions
Single dose administered based on weight
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Minutes to 12 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Is \<12 years of age and ≥3 kg to \<40 kg at the time parental/guardian consent is signed 2. Has at least one risk factor for developing severe COVID-19 if they were to become infected, such as: 1. Obesity (BMI \[kg/m2\] ≥95th percentile for age and sex based on CDC growth charts) 2. Cardiovascular disease 3. Chronic lung disease 4. Type 1 or type 2 diabetes mellitus 5. Chronic kidney disease, including those on dialysis 6. Chronic liver disease 7. 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) 8. Medical complexities (examples include any underlying genetic condition, neurologic condition, metabolic condition, or congenital heart disease) 9. Any other condition deemed by the Investigator to be a risk factor for severe COVID-19 Key
Exclusion criteria
1. 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. 2. Has active respiratory or non-respiratory symptoms consistent with COVID-19 in the opinion of the Investigator 3. Has subject-reported clinical history of COVID-19, as determined by Investigator, within the last 90 days 4. Has subject-reported history of prior Emergency Use Authorization (EUA)/approved positive diagnostic test for SARSCoV-2 infection within the last 90 days 5. Is currently hospitalized or was hospitalized for \>24 hours for any reason within 14 days of the screening visit 6. 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) 7. 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. 8. 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentrations of Casirivimab+Imdevimab in Serum Over Time. | Day 0 and Day 14 | Concentrations reported in milligrams per Liter (mg/L) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Through end of study, approximately 24 weeks | — |
| Number of Participants With Indicated Immunogenicity as Measured by ADA to Imdevimab Over Time | Up to 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 Severity of TEAEs | Through end of study, approximately 24 weeks | 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. |
Countries
United States
Participant flow
Pre-assignment details
A total of 7 participants were screened. All 7 enrolled into Group A (≥10 kg to \<40 kg). One discontinued at week 9 due to being lost to follow-up. Participants in Group A (≥10 kg to \<40 kg) were subsequently divided into 2 groups for analysis: Group A1 (≥20 kg to \<40 kg) and Group A2 (≥10 kg to \<20 kg) and received different doses. Two participants enrolled in Group A1, 5 enrolled in Group A2; all 7 participants were enrolled and treated.
Participants by arm
| Arm | Count |
|---|---|
| ≥20 kg to <40 kg Single dose of casirivimab+imdevimab, that was the body weight dose equivalent to the 1200 mg adult dose (600 mg of casirivimab and 600 mg of imdevimab) administered as 1 to 4 subcutaneous (SC) injections based on body weight. | 2 |
| ≥10 kg to <20 kg Single dose of casirivimab+imdevimab, that was the body weight dose equivalent to the 1200 mg adult dose (600 mg of casirivimab and 600 mg of imdevimab) administered as 1 to 4 subcutaneous (SC) injections based on body weight. | 5 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | ≥10 kg to <20 kg | Total | ≥20 kg to <40 kg |
|---|---|---|---|
| Age, Continuous | 3.0 Years STANDARD_DEVIATION 1.58 | 4.9 Years STANDARD_DEVIATION 3.53 | 9.5 Years STANDARD_DEVIATION 2.12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 6 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 6 Participants | 2 Participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 5 |
| other Total, other adverse events | 2 / 2 | 3 / 5 |
| serious Total, serious adverse events | 0 / 2 | 0 / 5 |
Outcome results
Primary
Concentrations of Casirivimab+Imdevimab in Serum Over Time.
Concentrations reported in milligrams per Liter (mg/L)
Time frame: Day 0 and Day 14
Population: Here 'n' = the number of evaluable participants at the specified time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ≥10 kg to <40 kg | Concentrations of Casirivimab+Imdevimab in Serum Over Time. | Day 0 | 0 mg/L | Standard Deviation 0 |
| ≥10 kg to <40 kg | Concentrations of Casirivimab+Imdevimab in Serum Over Time. | Day 14 | 239.0 mg/L | Standard Deviation 36.3 |
Secondary
Immunogenicity as Measured by NAb to Imdevimab Over Time
Time frame: Up to 24 weeks
Population: Neutralizing antibody (NAb) analysis data was not collected.
Secondary
Immunogenicity as Measured by Neutralizing Antibodies (NAb) to Casirivimab Over Time
Time frame: Up to 24 weeks
Population: Neutralizing antibody (NAb) analysis data was not collected.
Secondary
Number of Participants With Grade ≥3 Hypersensitivity Reactions
Time frame: Through Day 4
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ≥10 kg to <40 kg | Number of Participants With Grade ≥3 Hypersensitivity Reactions | 0 Participants |
| ≥10 kg to <20 kg | Number of Participants With Grade ≥3 Hypersensitivity Reactions | 0 Participants |
Secondary
Number of Participants With Grade ≥3 Injection Site Reactions
Time frame: Through Day 4
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ≥10 kg to <40 kg | Number of Participants With Grade ≥3 Injection Site Reactions | 0 Participants |
| ≥10 kg to <20 kg | Number of Participants With Grade ≥3 Injection Site Reactions | 0 Participants |
Secondary
Number of Participants With Indicated Immunogenicity as Measured by ADA to Imdevimab Over Time
Time frame: Up to 24 weeks
Population: Here 'n' = number of evaluable participants at the specified time point.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ≥10 kg to <40 kg | Number of Participants With Indicated Immunogenicity as Measured by ADA to Imdevimab Over Time | 2 Participants |
| ≥10 kg to <20 kg | Number of Participants With Indicated Immunogenicity as Measured by ADA to Imdevimab Over Time | 3 Participants |
Secondary
Number of Participants With Indicated Immunogenicity as Measured by Anti-drug Antibodies (ADA) to Casirivimab Over Time
Time frame: Up to 24 weeks
Population: Here 'n' = number of evaluable participants at the specified time point.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ≥10 kg to <40 kg | Number of Participants With Indicated Immunogenicity as Measured by Anti-drug Antibodies (ADA) to Casirivimab Over Time | 2 Participants |
| ≥10 kg to <20 kg | Number of Participants With Indicated Immunogenicity as Measured by Anti-drug Antibodies (ADA) to Casirivimab Over Time | 3 Participants |
Secondary
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.
Time frame: Through end of study, approximately 24 weeks
Population: The Safety Analysis Set (SAF) includes all participants who received any study drug; it is based on the treatment received (as treated).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ≥10 kg to <40 kg | Number of Participants With Indicated Severity of TEAEs | Infections and Infestations - Grade 4 | 0 Participants |
| ≥10 kg to <40 kg | Number of Participants With Indicated Severity of TEAEs | Respiratory, thoracic and mediastinal disorders - Grade 3 | 0 Participants |
| ≥10 kg to <40 kg | Number of Participants With Indicated Severity of TEAEs | Infections and Infestations - Grade 1 | 1 Participants |
| ≥10 kg to <40 kg | Number of Participants With Indicated Severity of TEAEs | Respiratory, thoracic and mediastinal disorders - Grade 4 | 0 Participants |
| ≥10 kg to <40 kg | Number of Participants With Indicated Severity of TEAEs | Infections and Infestations - Grade 5 | 0 Participants |
| ≥10 kg to <40 kg | Number of Participants With Indicated Severity of TEAEs | Respiratory, thoracic and mediastinal disorders - Grade 5 | 0 Participants |
| ≥10 kg to <40 kg | Number of Participants With Indicated Severity of TEAEs | Infections and Infestations - Grade 3 | 0 Participants |
| ≥10 kg to <40 kg | Number of Participants With Indicated Severity of TEAEs | Nervous system disorders - Grade 1 | 0 Participants |
| ≥10 kg to <40 kg | Number of Participants With Indicated Severity of TEAEs | Respiratory, thoracic and mediastinal disorders - Grade 1 | 0 Participants |
| ≥10 kg to <40 kg | Number of Participants With Indicated Severity of TEAEs | Nervous system disorders - Grade 2 | 0 Participants |
| ≥10 kg to <40 kg | Number of Participants With Indicated Severity of TEAEs | Infections and Infestations - Grade 2 | 1 Participants |
| ≥10 kg to <40 kg | Number of Participants With Indicated Severity of TEAEs | Nervous system disorders - Grade 3 | 0 Participants |
| ≥10 kg to <40 kg | Number of Participants With Indicated Severity of TEAEs | Respiratory, thoracic and mediastinal disorders - Grade 2 | 1 Participants |
| ≥10 kg to <40 kg | Number of Participants With Indicated Severity of TEAEs | Nervous system disorders - Grade 4 | 0 Participants |
| ≥10 kg to <40 kg | Number of Participants With Indicated Severity of TEAEs | Nervous system disorders - Grade 5 | 0 Participants |
| ≥10 kg to <20 kg | Number of Participants With Indicated Severity of TEAEs | Nervous system disorders - Grade 5 | 0 Participants |
| ≥10 kg to <20 kg | Number of Participants With Indicated Severity of TEAEs | Nervous system disorders - Grade 4 | 0 Participants |
| ≥10 kg to <20 kg | Number of Participants With Indicated Severity of TEAEs | Infections and Infestations - Grade 1 | 1 Participants |
| ≥10 kg to <20 kg | Number of Participants With Indicated Severity of TEAEs | Infections and Infestations - Grade 2 | 1 Participants |
| ≥10 kg to <20 kg | Number of Participants With Indicated Severity of TEAEs | Infections and Infestations - Grade 3 | 0 Participants |
| ≥10 kg to <20 kg | Number of Participants With Indicated Severity of TEAEs | Infections and Infestations - Grade 4 | 0 Participants |
| ≥10 kg to <20 kg | Number of Participants With Indicated Severity of TEAEs | Infections and Infestations - Grade 5 | 0 Participants |
| ≥10 kg to <20 kg | Number of Participants With Indicated Severity of TEAEs | Respiratory, thoracic and mediastinal disorders - Grade 1 | 1 Participants |
| ≥10 kg to <20 kg | Number of Participants With Indicated Severity of TEAEs | Respiratory, thoracic and mediastinal disorders - Grade 2 | 1 Participants |
| ≥10 kg to <20 kg | Number of Participants With Indicated Severity of TEAEs | Respiratory, thoracic and mediastinal disorders - Grade 3 | 0 Participants |
| ≥10 kg to <20 kg | Number of Participants With Indicated Severity of TEAEs | Respiratory, thoracic and mediastinal disorders - Grade 4 | 0 Participants |
| ≥10 kg to <20 kg | Number of Participants With Indicated Severity of TEAEs | Respiratory, thoracic and mediastinal disorders - Grade 5 | 0 Participants |
| ≥10 kg to <20 kg | Number of Participants With Indicated Severity of TEAEs | Nervous system disorders - Grade 1 | 1 Participants |
| ≥10 kg to <20 kg | Number of Participants With Indicated Severity of TEAEs | Nervous system disorders - Grade 2 | 0 Participants |
| ≥10 kg to <20 kg | Number of Participants With Indicated Severity of TEAEs | Nervous system disorders - Grade 3 | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: Through end of study, approximately 24 weeks
Population: The Safety Analysis Set (SAF) includes all participants who received any study drug; it is based on the treatment received (as treated).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ≥10 kg to <40 kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 2 Participants |
| ≥10 kg to <20 kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 3 Participants |