Relapsing Forms of Multiple Sclerosis
Conditions
Keywords
vaccine, pneumococcal, meningococcal, tetanus diphtheria, immune response
Brief summary
Primary objective is to evaluate the immune response to vaccination with tetanus diphtheria toxoids vaccine (Td) in participants with relapsing forms of Multiple Sclerosis (MS) who have been treated with Tecfidera (BG00012) versus those treated with non pegylated interferon (IFN). Secondary objective is to evaluate the immune response to vaccination with 23-valent pneumococcal polysaccharide vaccine (PPSV23) \[a mostly T cell-independent humoral response\] and meningococcal polysaccharide diphtheria conjugate vaccine, quadrivalent (MCV4) \[T cell-dependent neoantigen response\].
Interventions
DRUGdimethyl fumarate
Throughout the study participants will remain on their existing, stable dosing regimen of Tecfidera.
BIOLOGICALtetanus diphtheria toxoids vaccine
Administered as described in the treatment arm
Administered as described in the treatment arm
BIOLOGICALmeningococcal polysaccharide diphtheria conjugate vaccine (quadrivalent)
Administered as described in the treatment arm
DRUGnon-pegylated interferon
Throughout the study participants will remain on their existing, stable dosing regimen of non-pegylated IFN.
Sponsors
Biogen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Must have a confirmed diagnosis of relapsing remitting MS per the 2010 McDonald criteria. * Must have a known tetanus immunization history with most recent tetanus vaccination given 2 to 15 years prior to Screening and an anti-tetanus serum immunoglobulin titer at Screening that is less than or equal to one-half the upper limit of detection for the assay. * Must have been on a stable approved dose of Tecfidera (240 mg twice daily \[BID\]) \[Group 1\] for ≥6 months or on a stable approved dose of a non-pegylated IFN (e.g., Avonex, Betaseron, Rebif, Extavia) \[Group 2\] for ≥3 months prior to Day 1. Key
Exclusion criteria
* Clinical relapse requiring treatment within 30 days prior to Day 1. * Pneumococcal vaccination within 5 years prior to Screening. * Previous exposure to meningococcal vaccines. * Known hypersensitivity to Td, PPSV23, or MCV4 or their components. NOTE: Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Tetanus Responders (≥ 2-Fold Rise) at Day 28 Compared to Prevaccination Level | Up to Week 4 (Day 28) postvaccination | Percentage of participants with a ≥ 2-fold rise in anti-tetanus serum immunoglobulin G (IgG) levels (responders) from prevaccination to 4 weeks after Td vaccination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Pneumococcal Serotype 3 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level | Up to Week 4 (Day 28) postvaccination | Percentage of participants with a ≥ 2-fold rise in anti-pneumococcal serum IgG levels against serotype 3 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination. |
| Percentage of Pneumococcal Serotype 3 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level | Up to Week 4 (Day 28) postvaccination | Percentage of participants with a ≥ 4-fold rise in anti-pneumococcal serum IgG levels against serotype 3 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination. |
| Percentage of Pneumococcal Serotype 8 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level | Up to Week 4 (Day 28) postvaccination | Percentage of participants with a ≥ 2-fold rise in anti-pneumococcal serum IgG levels against serotype 8 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination. |
| Percentage of Pneumococcal Serotype 8 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level | Up to Week 4 (Day 28) postvaccination | Percentage of participants with a ≥ 4-fold rise in anti-pneumococcal serum IgG levels against serotype 8 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination. |
| Percentage of Meningococcal Serogroup C Responders (≥ 2-Fold Rise) Compared to Prevaccination Level | Up to Week 4 (Day 28) postvaccination | Percentage of participants with a ≥ 2-fold rise in anti-meningococcal serum IgG levels against serotype C from prevaccination to 4 weeks after MCV4 vaccination. |
| Percentage of Meningococcal Serogroup C Responders (≥ 4-Fold Rise) Compared to Prevaccination Level | Up to Week 4 (Day 28) postvaccination | Percentage of participants with a ≥ 4-fold rise in anti-meningococcal serum IgG levels against serotype C from prevaccination to 4 weeks after MCV4 vaccination. |
| Ratio of Serum Tetanus Level at Day 28 to Prevaccination | Up to Week 4 (Day 28) postvaccination | Median serum titer ratios from prevaccination to 4 weeks after Td vaccination. |
| Percentage of Tetanus Responders (≥ 4-Fold Rise) at Day 28 Compared to Prevaccination Level | Up to Week 4 (Day 28) postvaccination | Percentage of participants with a ≥ 4-fold rise in anti-tetanus serum IgG levels (responders) from prevaccination to 4 weeks after Td vaccination. |
| Ratio of Serum Pneumococcal Antibodies (Serotype 8) Level at Day 28 to Prevaccination | Up to Week 4 (Day 28) postvaccination | Median serum titer ratios from prevaccination to 4 weeks after PPSV23 vaccination. |
| Ratio of Serum Meningococcal Antibodies (Serogroup C) Level at Day 28 to Prevaccination | Up to Week 4 (Day 28) postvaccination | Median serum titer ratios from prevaccination to 4 weeks after MCV4 vaccination. |
| Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Day 1 to Week 4 | An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. A serious AE was any untoward medical occurrence that at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, could have jeopardized the participant or required intervention to prevent one of the other outcomes listed in the definition above. |
| Number of Participants With Shifts From Baseline in Hematology | Screening to Week 4 | Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high. |
| Number of Participants With Shifts From Baseline in Blood Chemistry | Screening to Week 4 | Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high. |
| Number of Participants With Abnormalities in Vital Signs | Screening to Week 4 | Temperature increase: \> 38 celcius (C) or ≥ 1 C increase from baseline. Pulse increase: \> 120 beats per minute (bpm) or \> 20 bpm increase from baseline. Pulse decrease: \< 50 bpm or \> 20 bpm decrease from baseline. Systolic blood pressure (SBP) increase: \> 180 millimeters of mercury (mmHg) or \> 40 mmHg from baseline. SBP decrease: \< 90 mmHg or \> 30 mmHg decrease from baseline. Diastolic blood pressure (DBP) increase: \> 105 mmHg or \> 30 mmHg increase from baseline. DBP decrease: \< 50 mmHg or \> 20 mmHg decrease from baseline. |
| Ratio of Serum Pneumococcal Antibodies (Serotype 3) Level at Day 28 to Prevaccination | Up to Week 4 (Day 28) postvaccination | Median serum titer ratios from prevaccination to 4 weeks after PPSV23 vaccination. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Non-Pegylated IFN Treated Plus Vaccinations Participants on a stable approved dose of a non pegylated IFN for ≥ 3 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL. | 33 |
| Tecfidera Treated Plus Vaccinations Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥ 6 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL. | 38 |
| Total | 71 |
Baseline characteristics
| Characteristic | Non-Pegylated IFN Treated Plus Vaccinations | Tecfidera Treated Plus Vaccinations | Total |
|---|---|---|---|
| Age, Continuous | 44.7 years STANDARD_DEVIATION 7.77 | 45.9 years STANDARD_DEVIATION 6.1 | 45.3 years STANDARD_DEVIATION 6.91 |
| Sex: Female, Male Female | 27 Participants | 34 Participants | 61 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 33 | 11 / 38 |
| serious Total, serious adverse events | 0 / 33 | 0 / 38 |
Outcome results
Primary
Percentage of Tetanus Responders (≥ 2-Fold Rise) at Day 28 Compared to Prevaccination Level
Percentage of participants with a ≥ 2-fold rise in anti-tetanus serum immunoglobulin G (IgG) levels (responders) from prevaccination to 4 weeks after Td vaccination.
Time frame: Up to Week 4 (Day 28) postvaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Pegylated IFN Treated Plus Vaccinations | Percentage of Tetanus Responders (≥ 2-Fold Rise) at Day 28 Compared to Prevaccination Level | 73 percentage of participants |
| Tecfidera Treated Plus Vaccinations | Percentage of Tetanus Responders (≥ 2-Fold Rise) at Day 28 Compared to Prevaccination Level | 68 percentage of participants |
p-value: 0.69295% CI: [-0.27, 0.19]Clopper-Pearson Exact
Secondary
Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs
An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. A serious AE was any untoward medical occurrence that at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, could have jeopardized the participant or required intervention to prevent one of the other outcomes listed in the definition above.
Time frame: Day 1 to Week 4
Population: Participants who received at least one vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Any Event | 18 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Moderate or Severe Event | 9 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Severe Event | 2 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Event Related to Existing Therapy | 3 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Serious Event | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Serious Event Related to Existing Therapy | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Serious Event Related to Td Vaccine | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Serious Event Related to PPSV23 Vaccine | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Serious Event Related to MCV4 Vaccine | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Withdrew From Study Due to an Event | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Serious Event Related to PPSV23 Vaccine | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Any Event | 16 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Serious Event Related to Existing Therapy | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Moderate or Severe Event | 7 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Withdrew From Study Due to an Event | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Severe Event | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Serious Event Related to Td Vaccine | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Event Related to Existing Therapy | 3 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Serious Event Related to MCV4 Vaccine | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs | Serious Event | 0 participants |
Secondary
Number of Participants With Abnormalities in Vital Signs
Temperature increase: \> 38 celcius (C) or ≥ 1 C increase from baseline. Pulse increase: \> 120 beats per minute (bpm) or \> 20 bpm increase from baseline. Pulse decrease: \< 50 bpm or \> 20 bpm decrease from baseline. Systolic blood pressure (SBP) increase: \> 180 millimeters of mercury (mmHg) or \> 40 mmHg from baseline. SBP decrease: \< 90 mmHg or \> 30 mmHg decrease from baseline. Diastolic blood pressure (DBP) increase: \> 105 mmHg or \> 30 mmHg increase from baseline. DBP decrease: \< 50 mmHg or \> 20 mmHg decrease from baseline.
Time frame: Screening to Week 4
Population: Participants who had a baseline assessment and at least one postbaseline assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Abnormalities in Vital Signs | Pulse Decrease | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Abnormalities in Vital Signs | SBP Decrease | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Abnormalities in Vital Signs | Pulse Increase | 1 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Abnormalities in Vital Signs | DBP Increase | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Abnormalities in Vital Signs | SBP Increase | 1 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Abnormalities in Vital Signs | DBP Decrease | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Abnormalities in Vital Signs | Temperature Increase | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Abnormalities in Vital Signs | DBP Decrease | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Abnormalities in Vital Signs | Temperature Increase | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Abnormalities in Vital Signs | Pulse Increase | 1 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Abnormalities in Vital Signs | Pulse Decrease | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Abnormalities in Vital Signs | SBP Increase | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Abnormalities in Vital Signs | SBP Decrease | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Abnormalities in Vital Signs | DBP Increase | 1 participants |
Secondary
Number of Participants With Shifts From Baseline in Blood Chemistry
Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high.
Time frame: Screening to Week 4
Population: n=participants whose baseline value was not low (or high) and who had at least one postbaseline value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Total Bilirubin: Shift to Low; n=32, 37 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Blood Urea Nitrogen: Shift to High; n=33, 38 | 1 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Aspartate Aminotransferase: Shift to High; n=33,36 | 1 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Creatinine: Shift to Low; n=33, 38 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Total Bilirubin: Shift to High; n=33, 38 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Creatinine: Shift to High; n=33, 37 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Alanine Aminotransferase: Shift to High; n=30, 35 | 2 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Sodium: Shift to Low; n=33, 38 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Gamma-glutamyl Transferase: Shift to Low; n=33, 38 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Sodium: Shift to High; n=33, 38 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Alanine Aminotransferase: Shift to Low; n=33, 38 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Potassium: Shift to Low; n=33, 38 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Gamma-glutamyl Transferase: Shift to High; n=33,38 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Potassium: Shift to High; n=33, 38 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Aspartate Aminotransferase: Shift to Low; n=33, 37 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Chloride: Shift to Low; n=33, 38 | 1 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Chloride: Shift to High; n=33, 38 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Blood Urea Nitrogen: Shift to Low; n=33, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Chloride: Shift to High; n=33, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Aspartate Aminotransferase: Shift to High; n=33,36 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Chloride: Shift to Low; n=33, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Alanine Aminotransferase: Shift to Low; n=33, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Alanine Aminotransferase: Shift to High; n=30, 35 | 1 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Total Bilirubin: Shift to Low; n=32, 37 | 1 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Total Bilirubin: Shift to High; n=33, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Gamma-glutamyl Transferase: Shift to Low; n=33, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Gamma-glutamyl Transferase: Shift to High; n=33,38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Blood Urea Nitrogen: Shift to Low; n=33, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Blood Urea Nitrogen: Shift to High; n=33, 38 | 1 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Creatinine: Shift to Low; n=33, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Creatinine: Shift to High; n=33, 37 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Sodium: Shift to Low; n=33, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Sodium: Shift to High; n=33, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Potassium: Shift to Low; n=33, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Potassium: Shift to High; n=33, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Blood Chemistry | Aspartate Aminotransferase: Shift to Low; n=33, 37 | 0 participants |
Secondary
Number of Participants With Shifts From Baseline in Hematology
Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high.
Time frame: Screening to Week 4
Population: n=participants whose baseline value was not low (or high) and who had at least one postbaseline value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Monocytes: Shift to Low; n=33, 38 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Hemoglobin: Shift to Low; n=28, 36 | 1 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Hemoglobin: Shift to High; n=32, 38 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Hematocrit: Shift to Low; n=31, 37 | 2 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Hematocrit: Shift to High; n=32, 38 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Red Blood Cell Count: Shift to Low; n=25, 32 | 1 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Red Blood Cell Count: Shift to High; n=33, 37 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | White Blood Cell Count: Shift to Low; n=27, 30 | 2 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | White Blood Cell Count: Shift to High; n=33, 38 | 2 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Neutrophils: Shift to Low; n=27, 34 | 3 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Neutrophils: Shift to High; n=33, 37 | 2 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Basophils: Shift to Low; n=33, 38 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Basophils: Shift to High; n=33, 38 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Monocytes: Shift to High; n=33, 38 | 2 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Lymphocytes: Shift to Low; n=33, 22 | 4 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Lymphocytes: Shift to High; n=33, 38 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Eosinophils: Shift to Low; n=33, 38 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Eosinophils: Shift to High; n=33, 38 | 0 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Platelet Count: Shift to Low; n=31, 38 | 1 participants |
| Non-Pegylated IFN Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Platelet Count: Shift to High; n=32, 37 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Eosinophils: Shift to High; n=33, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Monocytes: Shift to Low; n=33, 38 | 2 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Neutrophils: Shift to High; n=33, 37 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Hemoglobin: Shift to Low; n=28, 36 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Lymphocytes: Shift to High; n=33, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Hemoglobin: Shift to High; n=32, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Basophils: Shift to Low; n=33, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Hematocrit: Shift to Low; n=31, 37 | 1 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Platelet Count: Shift to High; n=32, 37 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Hematocrit: Shift to High; n=32, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Basophils: Shift to High; n=33, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Red Blood Cell Count: Shift to Low; n=25, 32 | 4 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Eosinophils: Shift to Low; n=33, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Red Blood Cell Count: Shift to High; n=33, 37 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Monocytes: Shift to High; n=33, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | White Blood Cell Count: Shift to Low; n=27, 30 | 4 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Platelet Count: Shift to Low; n=31, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | White Blood Cell Count: Shift to High; n=33, 38 | 0 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Lymphocytes: Shift to Low; n=33, 22 | 1 participants |
| Tecfidera Treated Plus Vaccinations | Number of Participants With Shifts From Baseline in Hematology | Neutrophils: Shift to Low; n=27, 34 | 2 participants |
Secondary
Percentage of Meningococcal Serogroup C Responders (≥ 2-Fold Rise) Compared to Prevaccination Level
Percentage of participants with a ≥ 2-fold rise in anti-meningococcal serum IgG levels against serotype C from prevaccination to 4 weeks after MCV4 vaccination.
Time frame: Up to Week 4 (Day 28) postvaccination
Population: One participant in the IFN group did not have an assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Pegylated IFN Treated Plus Vaccinations | Percentage of Meningococcal Serogroup C Responders (≥ 2-Fold Rise) Compared to Prevaccination Level | 53 percentage of participants |
| Tecfidera Treated Plus Vaccinations | Percentage of Meningococcal Serogroup C Responders (≥ 2-Fold Rise) Compared to Prevaccination Level | 53 percentage of participants |
p-value: 0.96795% CI: [-0.24, 0.23]Clopper-Pearson Exact
Secondary
Percentage of Meningococcal Serogroup C Responders (≥ 4-Fold Rise) Compared to Prevaccination Level
Percentage of participants with a ≥ 4-fold rise in anti-meningococcal serum IgG levels against serotype C from prevaccination to 4 weeks after MCV4 vaccination.
Time frame: Up to Week 4 (Day 28) postvaccination
Population: One participant in the IFN group did not have an assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Pegylated IFN Treated Plus Vaccinations | Percentage of Meningococcal Serogroup C Responders (≥ 4-Fold Rise) Compared to Prevaccination Level | 38 percentage of participants |
| Tecfidera Treated Plus Vaccinations | Percentage of Meningococcal Serogroup C Responders (≥ 4-Fold Rise) Compared to Prevaccination Level | 37 percentage of participants |
p-value: 0.95595% CI: [-0.24, 0.22]Clopper-Pearson Exact
Secondary
Percentage of Pneumococcal Serotype 3 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level
Percentage of participants with a ≥ 2-fold rise in anti-pneumococcal serum IgG levels against serotype 3 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination.
Time frame: Up to Week 4 (Day 28) postvaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Pegylated IFN Treated Plus Vaccinations | Percentage of Pneumococcal Serotype 3 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level | 79 percentage of participants |
| Tecfidera Treated Plus Vaccinations | Percentage of Pneumococcal Serotype 3 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level | 66 percentage of participants |
p-value: 0.22595% CI: [-0.35, 0.1]Clopper-Pearson Exact
Secondary
Percentage of Pneumococcal Serotype 3 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level
Percentage of participants with a ≥ 4-fold rise in anti-pneumococcal serum IgG levels against serotype 3 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination.
Time frame: Up to Week 4 (Day 28) postvaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Pegylated IFN Treated Plus Vaccinations | Percentage of Pneumococcal Serotype 3 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level | 70 percentage of participants |
| Tecfidera Treated Plus Vaccinations | Percentage of Pneumococcal Serotype 3 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level | 47 percentage of participants |
p-value: 0.05795% CI: [-0.44, 0.01]Clopper-Pearson Exact
Secondary
Percentage of Pneumococcal Serotype 8 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level
Percentage of participants with a ≥ 2-fold rise in anti-pneumococcal serum IgG levels against serotype 8 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination.
Time frame: Up to Week 4 (Day 28) postvaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Pegylated IFN Treated Plus Vaccinations | Percentage of Pneumococcal Serotype 8 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level | 88 percentage of participants |
| Tecfidera Treated Plus Vaccinations | Percentage of Pneumococcal Serotype 8 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level | 95 percentage of participants |
p-value: 0.395% CI: [-0.16, 0.3]Clopper-Pearson Exact
Secondary
Percentage of Pneumococcal Serotype 8 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level
Percentage of participants with a ≥ 4-fold rise in anti-pneumococcal serum IgG levels against serotype 8 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination.
Time frame: Up to Week 4 (Day 28) postvaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Pegylated IFN Treated Plus Vaccinations | Percentage of Pneumococcal Serotype 8 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level | 85 percentage of participants |
| Tecfidera Treated Plus Vaccinations | Percentage of Pneumococcal Serotype 8 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level | 82 percentage of participants |
p-value: 0.71495% CI: [-0.26, 0.2]Clopper-Pearson Exact
Secondary
Percentage of Tetanus Responders (≥ 4-Fold Rise) at Day 28 Compared to Prevaccination Level
Percentage of participants with a ≥ 4-fold rise in anti-tetanus serum IgG levels (responders) from prevaccination to 4 weeks after Td vaccination.
Time frame: Up to Week 4 (Day 28) postvaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Pegylated IFN Treated Plus Vaccinations | Percentage of Tetanus Responders (≥ 4-Fold Rise) at Day 28 Compared to Prevaccination Level | 61 percentage of participants |
| Tecfidera Treated Plus Vaccinations | Percentage of Tetanus Responders (≥ 4-Fold Rise) at Day 28 Compared to Prevaccination Level | 42 percentage of participants |
Comparison: Responders at Day 28p-value: 0.1295% CI: [-0.41, 0.05]Clopper-Pearson Exact
Secondary
Ratio of Serum Meningococcal Antibodies (Serogroup C) Level at Day 28 to Prevaccination
Median serum titer ratios from prevaccination to 4 weeks after MCV4 vaccination.
Time frame: Up to Week 4 (Day 28) postvaccination
Population: One participant in the IFN group did not have an assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-Pegylated IFN Treated Plus Vaccinations | Ratio of Serum Meningococcal Antibodies (Serogroup C) Level at Day 28 to Prevaccination | 3.300 ratio |
| Tecfidera Treated Plus Vaccinations | Ratio of Serum Meningococcal Antibodies (Serogroup C) Level at Day 28 to Prevaccination | 3.408 ratio |
Secondary
Ratio of Serum Pneumococcal Antibodies (Serotype 3) Level at Day 28 to Prevaccination
Median serum titer ratios from prevaccination to 4 weeks after PPSV23 vaccination.
Time frame: Up to Week 4 (Day 28) postvaccination
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-Pegylated IFN Treated Plus Vaccinations | Ratio of Serum Pneumococcal Antibodies (Serotype 3) Level at Day 28 to Prevaccination | 9.667 ratio |
| Tecfidera Treated Plus Vaccinations | Ratio of Serum Pneumococcal Antibodies (Serotype 3) Level at Day 28 to Prevaccination | 4.741 ratio |
Secondary
Ratio of Serum Pneumococcal Antibodies (Serotype 8) Level at Day 28 to Prevaccination
Median serum titer ratios from prevaccination to 4 weeks after PPSV23 vaccination.
Time frame: Up to Week 4 (Day 28) postvaccination
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-Pegylated IFN Treated Plus Vaccinations | Ratio of Serum Pneumococcal Antibodies (Serotype 8) Level at Day 28 to Prevaccination | 27.000 ratio |
| Tecfidera Treated Plus Vaccinations | Ratio of Serum Pneumococcal Antibodies (Serotype 8) Level at Day 28 to Prevaccination | 13.845 ratio |
Secondary
Ratio of Serum Tetanus Level at Day 28 to Prevaccination
Median serum titer ratios from prevaccination to 4 weeks after Td vaccination.
Time frame: Up to Week 4 (Day 28) postvaccination
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Non-Pegylated IFN Treated Plus Vaccinations | Ratio of Serum Tetanus Level at Day 28 to Prevaccination | 6.128 ratio |
| Tecfidera Treated Plus Vaccinations | Ratio of Serum Tetanus Level at Day 28 to Prevaccination | 4.463 ratio |