We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02097849
Recruitment Status : Completed
First Posted : March 27, 2014
Results First Posted : June 2, 2017
Last Update Posted : June 2, 2017
Sponsor:
Information provided by (Responsible Party):

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].


Condition or disease Intervention/treatment Phase
Relapsing Forms of Multiple Sclerosis Drug: dimethyl fumarate Biological: tetanus diphtheria toxoids vaccine Biological: 23-valent pneumococcal polysaccharide vaccine Biological: meningococcal polysaccharide diphtheria conjugate vaccine (quadrivalent) Drug: non-pegylated interferon Phase 2

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 71 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : February 28, 2015
Primary Completion Date : May 2, 2016
Study Completion Date : May 2, 2016


Arms and Interventions

Arm Intervention/treatment
Active Comparator: Non-Pegylated IFN Treated Plus Vaccinations

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

Biological: tetanus diphtheria toxoids vaccine
Administered as described in the treatment arm
Other Names:
  • Td
  • Tenivac
Biological: 23-valent pneumococcal polysaccharide vaccine
Administered as described in the treatment arm
Other Names:
  • Pneumovax 23
  • PPSV23
Biological: meningococcal polysaccharide diphtheria conjugate vaccine (quadrivalent)
Administered as described in the treatment arm
Other Names:
  • MCV4
  • Menveo
Drug: non-pegylated interferon
Throughout the study participants will remain on their existing, stable dosing regimen of non-pegylated IFN.
Other Name: IFN
Experimental: Tecfidera Treated Plus Vaccinations

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

Drug: dimethyl fumarate
Throughout the study participants will remain on their existing, stable dosing regimen of Tecfidera.
Other Names:
  • DMF
  • BG00012
  • Tecfidera
Biological: tetanus diphtheria toxoids vaccine
Administered as described in the treatment arm
Other Names:
  • Td
  • Tenivac
Biological: 23-valent pneumococcal polysaccharide vaccine
Administered as described in the treatment arm
Other Names:
  • Pneumovax 23
  • PPSV23
Biological: meningococcal polysaccharide diphtheria conjugate vaccine (quadrivalent)
Administered as described in the treatment arm
Other Names:
  • MCV4
  • Menveo


Outcome Measures

Primary Outcome Measures :
  1. Percentage of Tetanus Responders (≥ 2-Fold Rise) at Day 28 Compared to Prevaccination Level [ Time Frame: 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 :
  1. Percentage of Tetanus Responders (≥ 4-Fold Rise) at Day 28 Compared to Prevaccination Level [ Time Frame: 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.

  2. Percentage of Pneumococcal Serotype 3 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level [ Time Frame: 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.

  3. Percentage of Pneumococcal Serotype 3 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level [ Time Frame: 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.

  4. Percentage of Pneumococcal Serotype 8 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level [ Time Frame: 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.

  5. Percentage of Pneumococcal Serotype 8 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level [ Time Frame: 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.

  6. Percentage of Meningococcal Serogroup C Responders (≥ 2-Fold Rise) Compared to Prevaccination Level [ Time Frame: 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.

  7. Percentage of Meningococcal Serogroup C Responders (≥ 4-Fold Rise) Compared to Prevaccination Level [ Time Frame: 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.

  8. Ratio of Serum Tetanus Level at Day 28 to Prevaccination [ Time Frame: Up to Week 4 (Day 28) postvaccination ]
    Median serum titer ratios from prevaccination to 4 weeks after Td vaccination.

  9. Ratio of Serum Pneumococcal Antibodies (Serotype 3) Level at Day 28 to Prevaccination [ Time Frame: Up to Week 4 (Day 28) postvaccination ]
    Median serum titer ratios from prevaccination to 4 weeks after PPSV23 vaccination.

  10. Ratio of Serum Pneumococcal Antibodies (Serotype 8) Level at Day 28 to Prevaccination [ Time Frame: Up to Week 4 (Day 28) postvaccination ]
    Median serum titer ratios from prevaccination to 4 weeks after PPSV23 vaccination.

  11. Ratio of Serum Meningococcal Antibodies (Serogroup C) Level at Day 28 to Prevaccination [ Time Frame: Up to Week 4 (Day 28) postvaccination ]
    Median serum titer ratios from prevaccination to 4 weeks after MCV4 vaccination.

  12. Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs [ Time Frame: 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.

  13. Number of Participants With Shifts From Baseline in Hematology [ Time Frame: 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.

  14. Number of Participants With Shifts From Baseline in Blood Chemistry [ Time Frame: 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.

  15. Number of Participants With Abnormalities in Vital Signs [ Time Frame: 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.


Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02097849


Locations
United States, Arizona
Research Site
Gilbert, Arizona, United States, 85234
United States, Colorado
Research Site
Thornton, Colorado, United States, 80233
United States, Florida
Research Site
Fort Lauderdale, Florida, United States, 33312
Research Site
Sarasota, Florida, United States, 34243
United States, Indiana
Research Site
Indianapolis, Indiana, United States, 46202
United States, Kentucky
Research Site
Lexington, Kentucky, United States, 40513
United States, Maine
Research Site
Auburn, Maine, United States, 04210
United States, New York
Research Site
New York, New York, United States, 10016
United States, North Carolina
Research Site
Charlotte, North Carolina, United States, 28203
United States, Ohio
Research Site
Akron, Ohio, United States, 44320
Research Site
Cleveland, Ohio, United States, 44195
Research Site
Dayton, Ohio, United States, 45417
United States, Texas
Research Site
Round Rock, Texas, United States, 78761
Research Site
San Antonio, Texas, United States, 78258
Sponsors and Collaborators
Biogen
Investigators
Study Director: Medical Director Biogen
More Information

Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT02097849     History of Changes
Other Study ID Numbers: 109MS307
First Posted: March 27, 2014    Key Record Dates
Results First Posted: June 2, 2017
Last Update Posted: June 2, 2017
Last Verified: April 2017

Keywords provided by Biogen:
vaccine
pneumococcal
meningococcal
tetanus diphtheria
immune response

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Vaccines
Dimethyl Fumarate
Heptavalent Pneumococcal Conjugate Vaccine
Interferons
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Dermatologic Agents
Immunosuppressive Agents