Relapsing Multiple Sclerosis
Conditions
Keywords
ofatumumab, multiple sclerosis
Brief summary
To assess whether participants treated with ofatumumab 20 mg subcutaneous (s.c.) administered once every 4 weeks (q4) can mount an adequate immune response to inactivated influenza vaccine as measured by humoral responses compared to participants on an iDMT.
Detailed description
Vaccinations against influenza are an important part of effective management of multiple sclerosis (MS). Ofatumumab is a human anti-CD20 monoclonal antibody (mAb) which depletes B-cells, a component of the immune system. This study investigates if ofatumumab treated patients can have an immune response that may be protective after receiving the influenza vaccine. There were 3 study periods: * Screening Period of up to 1 week to assess eligibility requirements. * Investigational Period of 4 weeks All participants received an inactivated influenza vaccine within 9 calendar days after the Screening Visit, before the Week 0 Visit occurred. Participants in Cohort 1 received loading doses of 20 mg ofatumumab administered subcutaneously (s.c.) at Weeks 2, 3, and 4. Participants in Cohort 2 continued taking their prescribed ofatumumab as per their dosing schedule throughout the Investigational Period. Participants in Cohort 3 continued administration of their prescribed injectable disease modifying therapy (iDMT) as per their dosing schedule in the Investigational Period. • Optional, 6-month open-label Extension Period Participants in Cohort 1 were administered their first dose of ofatumumab at Week 6; thereinafter, they continued monthly dosing until the final dose at Week 26. Participants in Cohort 2 continued to receive ofatumumab monthly until the final dose at Week 28. Participants in Cohort 3 did not enter the open-label Extension Period.
Interventions
BIOLOGICALQuadrivalent influenza vaccine
2020-2021, 2021-2022, or 2022-2023 inactivated quadrivalent influenza vaccine. Participants received the vaccine within 9 calendar days after the Screening Visit, before the Week 0 Visit occurred.
DRUGOfatumumab
Auto-injector containing 20 mg ofatumumab (20 mg/0.4mL) for subcutaneous (s.c.) administration. * Participants in Cohort 1 received loading doses of 20 mg ofatumumab s.c. at Weeks 2, 3, and 4 in the Investigational Period. In the open-label Extension Period, they administered the first dose of ofatumumab at Week 6 and continued monthly dosing until the final dose at Week 26. Novartis supplied participants in Cohort 1 with ofatumumab treatment. * Participants in Cohort 2 continued on their commercially prescribed ofatumumab treatment during the Investigational Period. In the open-label Extension Period, they continued to administer ofatumumab monthly until the final dose at Week 28. Cohort 2 participants in the extension could have either remained on their prescribed ofatumumab or switched to study supplied ofatumumab.
DRUGiDMT
Participants in Cohort 3 continued on their commercially prescribed injectable disease modifying therapy (iDMT) during the Investigational Period.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Unblinded treatment
Intervention model description
Parallel, prospective study
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent must be obtained prior to participation in the study 2. Age 18-55 years old 3. Diagnosis of relapsing MS by 2017 revised McDonald criteria 4. Must be willing to comply with the study schedule 5. Planning to receive a 2020-2021, 2021-2022, or 2022-2023 inactivated influenza vaccine 6. Planning to start treatment with ofatumumab or already on commercially prescribed ofatumumab for at least 2 weeks prior to the screening visit Participants in Cohort 3 must fulfill criteria 1-5 above in addition to the following: 7. Participant must currently be receiving iDMT
Exclusion criteria
1. Already has received the 2020-2021, 2021-2022, or 2022-2023 season influenza vaccine 2. Known hypersensitivity to any component of the influenza vaccine 3. Any safety finding including low IgG and/or low IgM levels requiring an ofatumumab treatment interruption within the 12 weeks immediately prior to Week 0 4. Any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks prior to or oral antibiotics within two weeks prior to Week 0 5. Known clinical diagnosis of influenza infection during the 2020-2021 influenza season prior to starting the study based on investigator's or subject's personal physician's judgement (laboratory report of confirmed influenza infection is not required) 6. Prior treatment with B-cell targeted therapies (e.g., rituximab or ocrelizumab), lymphocyte-trafficking blockers, alemtuzumab, anti-CD4, cladribine, cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, bone marrow transplantation. Treatment with a natalizumab within 6 months of week 0 7. Treatment with an S1P modulator within 60 days prior to Week 0 8. Participants with any known active systemic bacterial, fungal or viral or fungal infections (such as hepatitis, progressive multifocal leukocencephalopathy, COVID-19 or HIV), or known to have acquired immunodeficiency syndrome (AIDS) 9. Participation in another interventional clinical trial within 14 days prior to the screening visit 10. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test 11. Women of child-bearing potential 12. Patients with a history of Guillain-Barre syndrome within 6 weeks of receiving the influenza vaccination.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Week 4 | A seroprotection responder was a participant achieving seroprotection as defined by a post-vaccination hemagglutination inhibition (HI) titer ≥ 40 at Week 4. Seroprotection against ten influenza strains was analyzed. The analysis was performed taking into consideration observed data. |
| Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Week 4 | A seroprotection responder was a participant achieving seroprotection as defined by a post-vaccination hemagglutination inhibition (HI) titer ≥ 40 at Week 4. Seroprotection against ten influenza strains was analyzed. Non-responder imputation (NRI) for missing data was applied. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Baseline (pre-vaccination), Week 4 | Seroconversion was defined as: • a ≥ 4-fold increase in HI titers after vaccination (in participants with pre-vaccination HI titers ≥ 10) OR • post-vaccination HI titers ≥ 40 (in participants with pre-vaccination HI titers \< 10) Seroconversion against ten influenza strains was analyzed. The analysis was performed taking into consideration observed data. |
| Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Baseline (pre-vaccination), Week 4 | Seroconversion was defined as: • a ≥ 4-fold increase in HI titers after vaccination (in participants with pre-vaccination HI titers ≥ 10) OR • post-vaccination HI titers ≥ 40 (in participants with pre-vaccination HI titers \< 10) Seroconversion against ten influenza strains was analyzed. Non-responder imputation (NRI) for missing data was applied. |
| Fold Change From Baseline in Hemagglutination Inhibition Titers | Baseline (pre-vaccination), Week 4 | Hemagglutination inhibition (HI) antibody titers were measured in serum samples pre-vaccination (baseline) and post-vaccination (Week 4). The geometric mean of the ratio of post-vaccination to pre-vaccination HI titer was calculated to estimate the average fold change in HI titer after vaccination compared to before vaccination. |
| Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation and Serious Adverse Events (SAEs) | From Week 0 to Week 26 (Cohort 1), Week 28 (Cohort 2) and Week 4 (Cohort 3) | Number of participants with adverse events (any AEs regardless of seriousness), AEs leading to study drug discontinuation and serious adverse events (SAEs). On-study AEs are defined as AEs which started or worsened on or after the date of the visit at Week 0. |
Countries
United States
Participant flow
Recruitment details
This study was conducted in 3 sites in the United States.
Pre-assignment details
Participants underwent a screening period of up to 1 week. After screening there was a 4-week investigational period and an optional 6-month open-label extension period.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Patients with relapsing multiple sclerosis (MS) receiving a 2020-2021, 2021-2022, or 2022-2023 inactivated influenza vaccine two weeks prior to ofatumumab start | 22 |
| Cohort 2 Patients with relapsing MS receiving a 2020-2021, 2021-2022, 2022-2023 inactivated influenza vaccine at least 4 weeks after ofatumumab start | 22 |
| Cohort 3 Patients with relapsing MS currently on iDMT receiving a 2020-2021, 2021-2022, or 2022-2023 inactivated influenza vaccine | 19 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Extension Period | Lost to Follow-up | 1 | 0 | 0 |
| Investigational Period | Lost to Follow-up | 0 | 0 | 1 |
| Investigational Period | Protocol Deviation | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Cohort 3 | Total |
|---|---|---|---|---|
| Age, Continuous | 41.4 years STANDARD_DEVIATION 8.88 | 38.9 years STANDARD_DEVIATION 9.03 | 43.3 years STANDARD_DEVIATION 7.12 | 41.1 years STANDARD_DEVIATION 8.5 |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 4 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 21 Participants | 18 Participants | 15 Participants | 54 Participants |
| Sex: Female, Male Female | 19 Participants | 15 Participants | 14 Participants | 48 Participants |
| Sex: Female, Male Male | 3 Participants | 7 Participants | 5 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 22 | 0 / 19 |
| other Total, other adverse events | 16 / 22 | 6 / 22 | 2 / 19 |
| serious Total, serious adverse events | 0 / 22 | 1 / 22 | 0 / 19 |
Outcome results
Primary
Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation)
A seroprotection responder was a participant achieving seroprotection as defined by a post-vaccination hemagglutination inhibition (HI) titer ≥ 40 at Week 4. Seroprotection against ten influenza strains was analyzed. Non-responder imputation (NRI) for missing data was applied.
Time frame: Week 4
Population: Safety Set including all participants who had received inactivated influenza vaccine and at last 1 dose of study drug. For each influenza strain, the number of participants analyzed corresponds to the participants with pre-vaccination HI titers for the corresponding strain.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Brisbane | 55.56 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Cambodia | 86.67 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Kansas | 55.56 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Michigan | 55.56 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Singapore | 55.56 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Victoria | 86.67 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Wisconsin | 53.33 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza B Colorado | 33.33 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza B Phuket | 63.64 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza B Washington | 66.67 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza B Phuket | 68.18 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Brisbane | 66.67 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Victoria | 100.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Singapore | 66.67 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Cambodia | 80.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza B Washington | 20.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza B Colorado | 33.33 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Kansas | 66.67 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Wisconsin | 40.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Michigan | 66.67 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza B Colorado | 100.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Michigan | 100.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Singapore | 100.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Victoria | 77.78 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza B Phuket | 68.42 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Wisconsin | 61.11 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Brisbane | 100.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza B Washington | 55.56 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Cambodia | 66.67 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Non-responder Imputation) | Influenza A Kansas | 100.00 percentage of participants |
Primary
Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case)
A seroprotection responder was a participant achieving seroprotection as defined by a post-vaccination hemagglutination inhibition (HI) titer ≥ 40 at Week 4. Seroprotection against ten influenza strains was analyzed. The analysis was performed taking into consideration observed data.
Time frame: Week 4
Population: Participants in the Safety Set with an available value for the outcome measure. Safety Set included all participants who had received inactivated influenza vaccine and at last 1 dose of study drug. For each influenza strain, the number of participants analyzed corresponds to the participants with both pre-vaccination and post-vaccination HI titers for the corresponding strain.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Brisbane | 100.00 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Cambodia | 100.00 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Kansas | 100.00 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Michigan | 100.00 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Singapore | 100.00 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Victoria | 100.00 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Wisconsin | 61.54 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza B Colorado | 60.00 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza B Phuket | 77.78 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza B Washington | 76.92 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza B Phuket | 68.18 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Brisbane | 100.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Victoria | 100.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Singapore | 100.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Cambodia | 80.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza B Washington | 20.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza B Colorado | 50.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Kansas | 100.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Wisconsin | 40.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Michigan | 100.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza B Colorado | 100.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Michigan | 100.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Singapore | 100.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Victoria | 100.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza B Phuket | 76.47 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Wisconsin | 68.75 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Brisbane | 100.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza B Washington | 71.43 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Cambodia | 85.71 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroprotection at Week 4 (Observed Case) | Influenza A Kansas | 100.00 percentage of participants |
Secondary
Fold Change From Baseline in Hemagglutination Inhibition Titers
Hemagglutination inhibition (HI) antibody titers were measured in serum samples pre-vaccination (baseline) and post-vaccination (Week 4). The geometric mean of the ratio of post-vaccination to pre-vaccination HI titer was calculated to estimate the average fold change in HI titer after vaccination compared to before vaccination.
Time frame: Baseline (pre-vaccination), Week 4
Population: Participants in the Safety Set with an available value for the outcome measure. Safety Set included all participants who had received inactivated influenza vaccine and at last 1 dose of study drug. For each influenza strain, the number of participants analyzed corresponds to the participants with both pre-vaccination and post-vaccination HI titers for the corresponding strain.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort 1 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Brisbane | 5.3 Ratio to baseline in HI titer |
| Cohort 1 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Cambodia | 9.4 Ratio to baseline in HI titer |
| Cohort 1 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Kansas | 2.6 Ratio to baseline in HI titer |
| Cohort 1 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Michigan | 5.5 Ratio to baseline in HI titer |
| Cohort 1 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Singapore | 4.3 Ratio to baseline in HI titer |
| Cohort 1 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Victoria | 8.6 Ratio to baseline in HI titer |
| Cohort 1 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Wisconsin | 4.9 Ratio to baseline in HI titer |
| Cohort 1 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza B Colorado | 3.0 Ratio to baseline in HI titer |
| Cohort 1 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza B Phuket | 3.8 Ratio to baseline in HI titer |
| Cohort 1 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza B Washington | 3.5 Ratio to baseline in HI titer |
| Cohort 2 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza B Phuket | 1.3 Ratio to baseline in HI titer |
| Cohort 2 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Brisbane | 1.4 Ratio to baseline in HI titer |
| Cohort 2 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Victoria | 1.3 Ratio to baseline in HI titer |
| Cohort 2 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Singapore | 1.0 Ratio to baseline in HI titer |
| Cohort 2 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Cambodia | 1.4 Ratio to baseline in HI titer |
| Cohort 2 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza B Washington | 0.9 Ratio to baseline in HI titer |
| Cohort 2 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza B Colorado | 1.4 Ratio to baseline in HI titer |
| Cohort 2 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Kansas | 1.0 Ratio to baseline in HI titer |
| Cohort 2 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Wisconsin | 1.7 Ratio to baseline in HI titer |
| Cohort 2 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Michigan | 0.9 Ratio to baseline in HI titer |
| Cohort 3 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza B Colorado | 4.0 Ratio to baseline in HI titer |
| Cohort 3 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Michigan | 4.0 Ratio to baseline in HI titer |
| Cohort 3 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Singapore | 2.0 Ratio to baseline in HI titer |
| Cohort 3 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Victoria | 3.6 Ratio to baseline in HI titer |
| Cohort 3 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza B Phuket | 2.2 Ratio to baseline in HI titer |
| Cohort 3 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Wisconsin | 2.6 Ratio to baseline in HI titer |
| Cohort 3 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Brisbane | 2.0 Ratio to baseline in HI titer |
| Cohort 3 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza B Washington | 2.8 Ratio to baseline in HI titer |
| Cohort 3 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Cambodia | 2.9 Ratio to baseline in HI titer |
| Cohort 3 | Fold Change From Baseline in Hemagglutination Inhibition Titers | Influenza A Kansas | 2.0 Ratio to baseline in HI titer |
Secondary
Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation and Serious Adverse Events (SAEs)
Number of participants with adverse events (any AEs regardless of seriousness), AEs leading to study drug discontinuation and serious adverse events (SAEs). On-study AEs are defined as AEs which started or worsened on or after the date of the visit at Week 0.
Time frame: From Week 0 to Week 26 (Cohort 1), Week 28 (Cohort 2) and Week 4 (Cohort 3)
Population: Safety Set including all participants who had received inactivated influenza vaccine and at last 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation and Serious Adverse Events (SAEs) | AEs leading to study drug discontinuation | 0 Participants |
| Cohort 1 | Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation and Serious Adverse Events (SAEs) | AEs | 16 Participants |
| Cohort 1 | Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 2 | Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation and Serious Adverse Events (SAEs) | AEs leading to study drug discontinuation | 0 Participants |
| Cohort 2 | Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation and Serious Adverse Events (SAEs) | AEs | 6 Participants |
| Cohort 2 | Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
| Cohort 3 | Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation and Serious Adverse Events (SAEs) | AEs | 2 Participants |
| Cohort 3 | Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 3 | Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation and Serious Adverse Events (SAEs) | AEs leading to study drug discontinuation | 0 Participants |
Secondary
Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation)
Seroconversion was defined as: • a ≥ 4-fold increase in HI titers after vaccination (in participants with pre-vaccination HI titers ≥ 10) OR • post-vaccination HI titers ≥ 40 (in participants with pre-vaccination HI titers \< 10) Seroconversion against ten influenza strains was analyzed. Non-responder imputation (NRI) for missing data was applied.
Time frame: Baseline (pre-vaccination), Week 4
Population: Safety Set including all participants who had received inactivated influenza vaccine and at last 1 dose of study drug. For each influenza strain, the number of participants analyzed corresponds to the participants with pre-vaccination HI titers for the corresponding strain.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Brisbane | 44.44 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Cambodia | 73.33 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Kansas | 22.22 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Michigan | 33.33 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Singapore | 22.22 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Victoria | 80.00 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Wisconsin | 40.00 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza B Colorado | 33.33 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza B Phuket | 40.91 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza B Washington | 33.33 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza B Phuket | 18.18 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Brisbane | 0.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Victoria | 20.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Singapore | 0.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Cambodia | 20.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza B Washington | 0.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza B Colorado | 0.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Kansas | 0.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Wisconsin | 10.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Michigan | 0.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza B Colorado | 100.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Michigan | 100.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Singapore | 0.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Victoria | 33.33 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza B Phuket | 36.84 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Wisconsin | 33.33 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Brisbane | 0.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza B Washington | 33.33 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Cambodia | 33.33 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Non-responder Imputation) | Influenza A Kansas | 0.00 percentage of participants |
Secondary
Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case)
Seroconversion was defined as: • a ≥ 4-fold increase in HI titers after vaccination (in participants with pre-vaccination HI titers ≥ 10) OR • post-vaccination HI titers ≥ 40 (in participants with pre-vaccination HI titers \< 10) Seroconversion against ten influenza strains was analyzed. The analysis was performed taking into consideration observed data.
Time frame: Baseline (pre-vaccination), Week 4
Population: Participants in the Safety Set with an available value for the outcome measure. Safety Set included all participants who had received inactivated influenza vaccine and at last 1 dose of study drug. For each influenza strain, the number of participants analyzed corresponds to the participants with both pre-vaccination and post-vaccination HI titers for the corresponding strain.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Brisbane | 80.00 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Cambodia | 84.62 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Kansas | 40.00 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Michigan | 60.00 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Singapore | 40.00 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Victoria | 92.31 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Wisconsin | 46.15 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza B Colorado | 60.00 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza B Phuket | 50.00 percentage of participants |
| Cohort 1 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza B Washington | 38.46 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza B Phuket | 18.18 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Brisbane | 0.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Victoria | 20.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Singapore | 0.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Cambodia | 20.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza B Washington | 0.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza B Colorado | 0.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Kansas | 0.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Wisconsin | 10.00 percentage of participants |
| Cohort 2 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Michigan | 0.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza B Colorado | 100.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Michigan | 100.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Singapore | 0.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Victoria | 42.86 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza B Phuket | 41.18 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Wisconsin | 37.50 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Brisbane | 0.00 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza B Washington | 42.86 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Cambodia | 42.86 percentage of participants |
| Cohort 3 | Percentage of Participants Achieving Seroconversion at Week 4 (Observed Case) | Influenza A Kansas | 0.00 percentage of participants |