Vaccination Response in Tecfidera-Treated Versus Interferon-Treated Participants With Relapsing Forms of Multiple Sclerosis.

Phase 2

Completed

Conditions: Relapsing Forms of Multiple Sclerosis

Interventions: Biological: tetanus diphtheria toxoids vaccine
Drug: dimethyl fumarate
Biological: 23-valent pneumococcal polysaccharide vaccine
Drug: non-pegylated interferon
Biological: meningococcal polysaccharide diphtheria conjugate vaccine (quadrivalent)

Registration Number: NCT02097849

Lead Sponsor: Biogen

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) \[T cell-dependent neoantigen response\].

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 71

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/exclusion criteria may apply.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Non-Pegylated IFN Treated Plus Vaccinations	non-pegylated interferon	Participants on a stable approved dose of a non pegylated IFN for ≥3 months will receive 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL PPSV23 0.5 mL MCV4 0.5 mL
Non-Pegylated IFN Treated Plus Vaccinations	tetanus diphtheria toxoids vaccine	Participants on a stable approved dose of a non pegylated IFN for ≥3 months will receive 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL PPSV23 0.5 mL MCV4 0.5 mL
Tecfidera Treated Plus Vaccinations	meningococcal polysaccharide diphtheria conjugate vaccine (quadrivalent)	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥6 months will receive 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL PPSV23 0.5 mL MCV4 0.5 mL
Non-Pegylated IFN Treated Plus Vaccinations	23-valent pneumococcal polysaccharide vaccine	Participants on a stable approved dose of a non pegylated IFN for ≥3 months will receive 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL PPSV23 0.5 mL MCV4 0.5 mL
Tecfidera Treated Plus Vaccinations	23-valent pneumococcal polysaccharide vaccine	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥6 months will receive 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL PPSV23 0.5 mL MCV4 0.5 mL
Tecfidera Treated Plus Vaccinations	tetanus diphtheria toxoids vaccine	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥6 months will receive 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL PPSV23 0.5 mL MCV4 0.5 mL
Non-Pegylated IFN Treated Plus Vaccinations	meningococcal polysaccharide diphtheria conjugate vaccine (quadrivalent)	Participants on a stable approved dose of a non pegylated IFN for ≥3 months will receive 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL PPSV23 0.5 mL MCV4 0.5 mL
Tecfidera Treated Plus Vaccinations	dimethyl fumarate	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥6 months will receive 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL PPSV23 0.5 mL MCV4 0.5 mL

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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.
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 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.
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 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 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.
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.
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.
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.
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.
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.