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

Primary Purpose

Relapsing Forms of Multiple Sclerosis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
dimethyl fumarate
tetanus diphtheria toxoids vaccine
23-valent pneumococcal polysaccharide vaccine
meningococcal polysaccharide diphtheria conjugate vaccine (quadrivalent)
non-pegylated interferon
Sponsored by
Biogen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsing Forms of Multiple Sclerosis focused on measuring vaccine, pneumococcal, meningococcal, tetanus diphtheria, immune response

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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/exclusion criteria may apply.

Sites / Locations

  • Research Site
  • Research Site
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  • Research Site
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  • Research Site
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Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Non-Pegylated IFN Treated Plus Vaccinations

Tecfidera Treated Plus Vaccinations

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
Ratio of Serum Tetanus Level at Day 28 to Prevaccination
Median serum titer ratios from prevaccination to 4 weeks after Td vaccination.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
March 25, 2014
Last Updated
May 1, 2017
Sponsor
Biogen
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1. Study Identification

Unique Protocol Identification Number
NCT02097849
Brief Title
Vaccination Response in Tecfidera-Treated Versus Interferon-Treated Participants With Relapsing Forms of Multiple Sclerosis.
Official Title
An Open-Label Study to Assess the Immune Response to Vaccination in Tecfidera® (BG00012)-Treated Versus Interferon-Treated Subjects With Relapsing Forms of Multiple Sclerosis.
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
February 28, 2015 (Actual)
Primary Completion Date
May 2, 2016 (Actual)
Study Completion Date
May 2, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen

4. Oversight

Data Monitoring Committee
No

5. Study Description

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].

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsing Forms of Multiple Sclerosis
Keywords
vaccine, pneumococcal, meningococcal, tetanus diphtheria, immune response

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
71 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Non-Pegylated IFN Treated Plus Vaccinations
Arm Type
Active Comparator
Arm Description
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
Arm Title
Tecfidera Treated Plus Vaccinations
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
dimethyl fumarate
Other Intervention Name(s)
DMF, BG00012, Tecfidera
Intervention Description
Throughout the study participants will remain on their existing, stable dosing regimen of Tecfidera.
Intervention Type
Biological
Intervention Name(s)
tetanus diphtheria toxoids vaccine
Other Intervention Name(s)
Td, Tenivac
Intervention Description
Administered as described in the treatment arm
Intervention Type
Biological
Intervention Name(s)
23-valent pneumococcal polysaccharide vaccine
Other Intervention Name(s)
Pneumovax 23, PPSV23
Intervention Description
Administered as described in the treatment arm
Intervention Type
Biological
Intervention Name(s)
meningococcal polysaccharide diphtheria conjugate vaccine (quadrivalent)
Other Intervention Name(s)
MCV4, Menveo
Intervention Description
Administered as described in the treatment arm
Intervention Type
Drug
Intervention Name(s)
non-pegylated interferon
Other Intervention Name(s)
IFN
Intervention Description
Throughout the study participants will remain on their existing, stable dosing regimen of non-pegylated IFN.
Primary Outcome Measure Information:
Title
Percentage of Tetanus Responders (≥ 2-Fold Rise) at Day 28 Compared to Prevaccination Level
Description
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
Secondary Outcome Measure Information:
Title
Percentage of Tetanus Responders (≥ 4-Fold Rise) at Day 28 Compared to Prevaccination Level
Description
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
Title
Percentage of Pneumococcal Serotype 3 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level
Description
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
Title
Percentage of Pneumococcal Serotype 3 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level
Description
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
Title
Percentage of Pneumococcal Serotype 8 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level
Description
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
Title
Percentage of Pneumococcal Serotype 8 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level
Description
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
Title
Percentage of Meningococcal Serogroup C Responders (≥ 2-Fold Rise) Compared to Prevaccination Level
Description
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
Title
Percentage of Meningococcal Serogroup C Responders (≥ 4-Fold Rise) Compared to Prevaccination Level
Description
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
Title
Ratio of Serum Tetanus Level at Day 28 to Prevaccination
Description
Median serum titer ratios from prevaccination to 4 weeks after Td vaccination.
Time Frame
Up to Week 4 (Day 28) postvaccination
Title
Ratio of Serum Pneumococcal Antibodies (Serotype 3) Level at Day 28 to Prevaccination
Description
Median serum titer ratios from prevaccination to 4 weeks after PPSV23 vaccination.
Time Frame
Up to Week 4 (Day 28) postvaccination
Title
Ratio of Serum Pneumococcal Antibodies (Serotype 8) Level at Day 28 to Prevaccination
Description
Median serum titer ratios from prevaccination to 4 weeks after PPSV23 vaccination.
Time Frame
Up to Week 4 (Day 28) postvaccination
Title
Ratio of Serum Meningococcal Antibodies (Serogroup C) Level at Day 28 to Prevaccination
Description
Median serum titer ratios from prevaccination to 4 weeks after MCV4 vaccination.
Time Frame
Up to Week 4 (Day 28) postvaccination
Title
Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs
Description
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
Title
Number of Participants With Shifts From Baseline in Hematology
Description
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
Title
Number of Participants With Shifts From Baseline in Blood Chemistry
Description
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
Title
Number of Participants With Abnormalities in Vital Signs
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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/exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Facility Name
Research Site
City
Thornton
State/Province
Colorado
ZIP/Postal Code
80233
Country
United States
Facility Name
Research Site
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33312
Country
United States
Facility Name
Research Site
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34243
Country
United States
Facility Name
Research Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Research Site
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40513
Country
United States
Facility Name
Research Site
City
Auburn
State/Province
Maine
ZIP/Postal Code
04210
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Research Site
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Research Site
City
Akron
State/Province
Ohio
ZIP/Postal Code
44320
Country
United States
Facility Name
Research Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Research Site
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45417
Country
United States
Facility Name
Research Site
City
Round Rock
State/Province
Texas
ZIP/Postal Code
78761
Country
United States
Facility Name
Research Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78258
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29159204
Citation
von Hehn C, Howard J, Liu S, Meka V, Pultz J, Mehta D, Prada C, Ray S, Edwards MR, Sheikh SI. Immune response to vaccines is maintained in patients treated with dimethyl fumarate. Neurol Neuroimmunol Neuroinflamm. 2017 Nov 15;5(1):e409. doi: 10.1212/NXI.0000000000000409. eCollection 2018 Jan.
Results Reference
derived

Learn more about this trial

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

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