Immunocompromised
Conditions
Keywords
Non-response to COVID-19 vaccination, COVID-19, Immunocompromised, weakened immune system
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
Interventions
Co-administered sequentially subcutaneous (SC)
DRUGPlacebo
Administered SC
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of Symptomatic (Broad Term), RT-PCR-confirmed SARS-CoV-2 Infection Cases During the EAP | The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days | Cumulative incidence of symptomatic (broad term), RT-PCR-confirmed SARS-CoV-2 infection cases during the Efficacy Assessment Period (EAP) |
Secondary
| Measure | Time frame |
|---|---|
| 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) |
| 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 |
| 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 |
| 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 |
Countries
Mexico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo matching casirivimab+imdevimab - Subcutaneous (SC) dose every 4 weeks (Q4W) | 16 |
| Casirivimab+Imdevimab Initial + Q4W Initial subcutaneous (SC) dose, then SC dose every 4 weeks (Q4W) | 17 |
| Casirivimab+Imdevimab Q4W casirivimab+imdevimab - Subcutaneous (SC) dose every 4 weeks (Q4W) | 16 |
| Casirivimab+Imdevimab Q12W casirivimab+imdevimab - Subcutaneous (SC) dose every 12 weeks (Q12W) | 17 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 0 | 1 |
| Overall Study | Death | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 2 | 0 |
| Overall Study | Sponsor Request | 0 | 1 | 1 | 0 |
| Overall Study | Subject Decision | 8 | 6 | 4 | 5 |
Baseline characteristics
| Characteristic | Placebo | Casirivimab+Imdevimab Initial + Q4W | Casirivimab+Imdevimab Q4W | Casirivimab+Imdevimab Q12W | Total |
|---|---|---|---|---|---|
| Age, Continuous | 60.1 years STANDARD_DEVIATION 14.16 | 60.0 years STANDARD_DEVIATION 12.87 | 59.2 years STANDARD_DEVIATION 11.67 | 58.2 years STANDARD_DEVIATION 13.99 | 59.4 years STANDARD_DEVIATION 12.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 15 Participants | 14 Participants | 14 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 16 Participants | 16 Participants | 15 Participants | 14 Participants | 61 Participants |
| Sex: Female, Male Female | 12 Participants | 10 Participants | 11 Participants | 10 Participants | 43 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 5 Participants | 7 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 16 | 1 / 17 | 0 / 16 | 0 / 17 |
| other Total, other adverse events | 7 / 16 | 5 / 17 | 10 / 16 | 8 / 17 |
| serious Total, serious adverse events | 1 / 16 | 1 / 17 | 0 / 16 | 2 / 17 |
Outcome results
Primary
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)
Time frame: The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Cumulative Incidence of Symptomatic (Broad Term), RT-PCR-confirmed SARS-CoV-2 Infection Cases During the EAP | 38.1 Cumulative Incidence Percentage |
| Casirivimab+Imdevimab Initial + Q4W | Cumulative Incidence of Symptomatic (Broad Term), RT-PCR-confirmed SARS-CoV-2 Infection Cases During the EAP | 14.3 Cumulative Incidence Percentage |
| Casirivimab+Imdevimab Q4W | Cumulative Incidence of Symptomatic (Broad Term), RT-PCR-confirmed SARS-CoV-2 Infection Cases During the EAP | 30.4 Cumulative Incidence Percentage |
| Casirivimab+Imdevimab Q12W | Cumulative Incidence of Symptomatic (Broad Term), RT-PCR-confirmed SARS-CoV-2 Infection Cases During the EAP | 21.4 Cumulative Incidence Percentage |
95% CI: [0.093, 3.393]Cox proportional hazard model
95% CI: [0.072, 2.929]Cox proportional hazard model
95% CI: [0.101, 3.668]Cox proportional hazard model
Secondary
Concentration of Casirivimab Over Time
Time frame: Up to 28 days postdose for the Q4W groups and 84 days postdose for the Q12 group
Population: The pharmacokinetic analysis set (PKAS) is defined for each analyte separately and includes all treated participants who received any amount of study drug (active or placebo \[SAF\]), and who had at least 1 non-missing result of respective total analyte following the first dose of study drug or placebo. The PKAS is based on the actual treatment received (as treated) rather than as randomized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Concentration of Casirivimab Over Time | 7 Days post-dose | 56.9 mg/L | Standard Deviation 18.2 |
| Placebo | Concentration of Casirivimab Over Time | 0 Days post-dose | 0 mg/L | Standard Deviation 0 |
| Placebo | Concentration of Casirivimab Over Time | 28 Days post-dose | 41.7 mg/L | Standard Deviation 13.6 |
| Casirivimab+Imdevimab Initial + Q4W | Concentration of Casirivimab Over Time | 7 Days post-dose | 15.3 mg/L | Standard Deviation 3.87 |
| Casirivimab+Imdevimab Initial + Q4W | Concentration of Casirivimab Over Time | 0 Days post-dose | 0 mg/L | Standard Deviation 0 |
| Casirivimab+Imdevimab Initial + Q4W | Concentration of Casirivimab Over Time | 28 Days post-dose | 10.7 mg/L | Standard Deviation 3.4 |
| Casirivimab+Imdevimab Q4W | Concentration of Casirivimab Over Time | 0 Days post-dose | 0 mg/L | Standard Deviation 0 |
| Casirivimab+Imdevimab Q4W | Concentration of Casirivimab Over Time | 28 Days post-dose | 10.7 mg/L | Standard Deviation 4.68 |
| Casirivimab+Imdevimab Q4W | Concentration of Casirivimab Over Time | 7 Days post-dose | 11.8 mg/L | Standard Deviation 5.01 |
Secondary
Concentration of Imdevimab Over Time
Time frame: Up to 28 days postdose for the Q4W groups and 84 days postdose for the Q12 group
Population: The pharmacokinetic analysis set (PKAS) is defined for each analyte separately and includes all treated participants who received any amount of study drug (active or placebo \[SAF\]), and who had at least 1 non-missing result of respective total analyte following the first dose of study drug or placebo. The PKAS is based on the actual treatment received (as treated) rather than as randomized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Concentration of Imdevimab Over Time | 7 Days post-dose | 51.5 mg/L | Standard Deviation 17.5 |
| Placebo | Concentration of Imdevimab Over Time | 0 Days post-dose | 0 mg/L | Standard Deviation 0 |
| Placebo | Concentration of Imdevimab Over Time | 28 Days post-dose | 35.7 mg/L | Standard Deviation 9.45 |
| Casirivimab+Imdevimab Initial + Q4W | Concentration of Imdevimab Over Time | 7 Days post-dose | 15.2 mg/L | Standard Deviation 5.37 |
| Casirivimab+Imdevimab Initial + Q4W | Concentration of Imdevimab Over Time | 0 Days post-dose | 0 mg/L | Standard Deviation 0 |
| Casirivimab+Imdevimab Initial + Q4W | Concentration of Imdevimab Over Time | 28 Days post-dose | 9.16 mg/L | Standard Deviation 3.37 |
| Casirivimab+Imdevimab Q4W | Concentration of Imdevimab Over Time | 0 Days post-dose | 0 mg/L | Standard Deviation 0 |
| Casirivimab+Imdevimab Q4W | Concentration of Imdevimab Over Time | 28 Days post-dose | 9.16 mg/L | Standard Deviation 4.73 |
| Casirivimab+Imdevimab Q4W | Concentration of Imdevimab Over Time | 7 Days post-dose | 11.7 mg/L | Standard Deviation 6.07 |
Secondary
Incidence of Adverse Events of Special Interest (AESIs) During the EAP
Time frame: The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Incidence of Adverse Events of Special Interest (AESIs) During the EAP | 0 Participants |
| Casirivimab+Imdevimab Initial + Q4W | Incidence of Adverse Events of Special Interest (AESIs) During the EAP | 0 Participants |
| Casirivimab+Imdevimab Q4W | Incidence of Adverse Events of Special Interest (AESIs) During the EAP | 0 Participants |
| Casirivimab+Imdevimab Q12W | Incidence of Adverse Events of Special Interest (AESIs) During the EAP | 0 Participants |
Secondary
Incidence of Anti-drug Antibodies (ADA) Over Time
Time frame: Up to 28 days postdose for the Q4W groups and 84 days postdose for the Q12 group
Population: The ADA analysis set (AAS) is defined for each study drug separately and includes all treated participants who received any amount of study drug (active or placebo \[SAF\]) and had at least 1 non-missing ADA result following the first dose of study drug or placebo. The AAS is based on the actual treatment received (as treated) rather than as randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Incidence of Anti-drug Antibodies (ADA) Over Time | 11 Participants |
| Casirivimab+Imdevimab Initial + Q4W | Incidence of Anti-drug Antibodies (ADA) Over Time | 12 Participants |
| Casirivimab+Imdevimab Q4W | Incidence of Anti-drug Antibodies (ADA) Over Time | 11 Participants |
| Casirivimab+Imdevimab Q12W | Incidence of Anti-drug Antibodies (ADA) Over Time | 13 Participants |
Secondary
Incidence of Neutralizing Antibodies (NAb) to Each mAb Over Time
Time frame: Up to 28 days postdose for the Q4W groups and 84 days postdose for the Q12 group
Population: The NAb analysis sets (NAbAS) comprises all treated participants (active or placebo) that were included in the AAS and tested negative at all ADA sampling times or tested positive at 1 or more post dose ADA sampling times and had at least 1 non-missing post dose NAb result (imputed or analysis result). The ADA analysis set (AAS) includes all treated participants who received any amount of study drug and had at least 1 non-missing ADA result following the first dose of study drug or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Incidence of Neutralizing Antibodies (NAb) to Each mAb Over Time | 11 Participants |
| Casirivimab+Imdevimab Initial + Q4W | Incidence of Neutralizing Antibodies (NAb) to Each mAb Over Time | 12 Participants |
| Casirivimab+Imdevimab Q4W | Incidence of Neutralizing Antibodies (NAb) to Each mAb Over Time | 11 Participants |
| Casirivimab+Imdevimab Q12W | Incidence of Neutralizing Antibodies (NAb) to Each mAb Over Time | 13 Participants |
Secondary
Number of Participants With Grade ≥3 Treatment-emergent Adverse Events (TEAEs) During the EAP
Time frame: The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days
Population: The safety analysis set (SAF) included all participants who received any study drug; it was based on the treatment received (as treated). Determination of as treated was based on the actual study drug received. Treatment compliance/administration and all clinical safety variables was analyzed using the SAF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Grade ≥3 Treatment-emergent Adverse Events (TEAEs) During the EAP | 0 Participants |
| Casirivimab+Imdevimab Initial + Q4W | Number of Participants With Grade ≥3 Treatment-emergent Adverse Events (TEAEs) During the EAP | 0 Participants |
| Casirivimab+Imdevimab Q4W | Number of Participants With Grade ≥3 Treatment-emergent Adverse Events (TEAEs) During the EAP | 0 Participants |
| Casirivimab+Imdevimab Q12W | Number of Participants With Grade ≥3 Treatment-emergent Adverse Events (TEAEs) During the EAP | 1 Participants |
Secondary
Number of Participants With Grade ≥3 Treatment-emergent Adverse Events (TEAEs) During the Follow-Up Period
Time frame: End of EAP to the end of the Follow-Up Period (Day 169 to 205, approximately ~1 months)
Population: The safety analysis set (SAF) included all participants who received any study drug; it was based on the treatment received (as treated). Determination of as treated was based on the actual study drug received. Treatment compliance/administration and all clinical safety variables was analyzed using the SAF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Grade ≥3 Treatment-emergent Adverse Events (TEAEs) During the Follow-Up Period | 1 Participants |
| Casirivimab+Imdevimab Initial + Q4W | Number of Participants With Grade ≥3 Treatment-emergent Adverse Events (TEAEs) During the Follow-Up Period | 0 Participants |
| Casirivimab+Imdevimab Q4W | Number of Participants With Grade ≥3 Treatment-emergent Adverse Events (TEAEs) During the Follow-Up Period | 0 Participants |
| Casirivimab+Imdevimab Q12W | Number of Participants With Grade ≥3 Treatment-emergent Adverse Events (TEAEs) During the Follow-Up Period | 1 Participants |
Secondary
Number of Participants With TEAEs Leading to Study Drug Discontinuation During the EAP
Time frame: The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With TEAEs Leading to Study Drug Discontinuation During the EAP | 0 Participants |
| Casirivimab+Imdevimab Initial + Q4W | Number of Participants With TEAEs Leading to Study Drug Discontinuation During the EAP | 1 Participants |
| Casirivimab+Imdevimab Q4W | Number of Participants With TEAEs Leading to Study Drug Discontinuation During the EAP | 0 Participants |
| Casirivimab+Imdevimab Q12W | Number of Participants With TEAEs Leading to Study Drug Discontinuation During the EAP | 1 Participants |
Secondary
Number of Participants With TEAEs Leading to Study Drug Discontinuation During the Follow-Up Period
Time frame: End of EAP to the end of the Follow-Up Period (Day 169 to 205, approximately ~1 months)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With TEAEs Leading to Study Drug Discontinuation During the Follow-Up Period | 0 Participants |
| Casirivimab+Imdevimab Initial + Q4W | Number of Participants With TEAEs Leading to Study Drug Discontinuation During the Follow-Up Period | 1 Participants |
| Casirivimab+Imdevimab Q4W | Number of Participants With TEAEs Leading to Study Drug Discontinuation During the Follow-Up Period | 0 Participants |
| Casirivimab+Imdevimab Q12W | Number of Participants With TEAEs Leading to Study Drug Discontinuation During the Follow-Up Period | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the EAP
Time frame: The EAP was defined as the day from first dose of study drug to day 169 +/- 7 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the EAP | 0 Participants |
| Casirivimab+Imdevimab Initial + Q4W | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the EAP | 0 Participants |
| Casirivimab+Imdevimab Q4W | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the EAP | 0 Participants |
| Casirivimab+Imdevimab Q12W | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the EAP | 1 Participants |
Secondary
Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the Follow-Up Period
Time frame: End of EAP to the end of the Follow-Up Period (Day 169 to 205, approximately ~1 months)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the Follow-Up Period | 1 Participants |
| Casirivimab+Imdevimab Initial + Q4W | Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the Follow-Up Period | 1 Participants |
| Casirivimab+Imdevimab Q4W | Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the Follow-Up Period | 0 Participants |
| Casirivimab+Imdevimab Q12W | Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the Follow-Up Period | 1 Participants |