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Tecfidera Slow-Titration Study (TITRATION)

Primary Purpose

Multiple Sclerosis

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
dimethyl fumarate
Sponsored by
Biogen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • Diagnosis of MS consistent with locally labeled indication for DMF
  • No prior treatment with DMF
  • Female subjects of childbearing potential who are not surgically sterile and male subjects must practice effective contraception during their participation in the study
  • Have had a recent complete blood count (CBC), including lymphocyte count, that does not preclude participation in the study, in the judgement of the investigator

Key Exclusion Criteria:

  • Have a recent history or ongoing GI illness (e.g., peptic ulcer, irritable bowel syndrome) or any other current condition with GI signs and symptoms (e.g., nausea, vomiting, abdominal pain, or diarrhea) that may interfere with assessment of study endpoints
  • Have other major comorbid conditions that preclude participation in the study, as determined by the investigator
  • Participant is pregnant, breastfeeding, or planning a pregnancy during the study period
  • Are receiving concomitant disease-modifying therapies for MS including, but not limited to, natalizumab, interferon beta, glatiramer acetate, fingolimod, alemtuzumab, teriflunomide, or laquinimod at screening
  • History of severe allergic or anaphylactic reactions or known drug hypersensitivity
  • NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard Treatment (One-Week Titration)

Slow Up-Titration (Six-Week Titration)

Arm Description

120 mg DMF twice daily for 1 week, then 240 mg (as 2 120-mg capsules) DMF twice daily for 11 weeks

120 mg DMF once daily (morning dose) and placebo once daily (evening dose) for 2 weeks, then 120 mg DMF twice daily for 2 weeks, then 240 mg (as 2 120-mg capsules) DMF in the morning and 120 mg in the evening for 2 weeks, then 240 mg (as 2 120-mg capsules) DMF twice daily for 6 weeks

Outcomes

Primary Outcome Measures

Proportion of Participants With a Worsening in Severity of Gastrointestinal (GI) Adverse Events (AEs) on the Gastrointestinal Symptom Rating Scale (GSRS)
The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms. A higher score relative to Baseline indicates worsening of severity.

Secondary Outcome Measures

Average Change From Baseline in GSRS Scores During DMF Treatment
Average change from baseline in GSRS scores over the 12 weeks of DMF treatment as measured by the total change in GSRS scores from baseline divided by the total number of days with GSRS scores recorded. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms.
Time to First Worsening From Baseline in GSRS Score
The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms. A higher score relative to Baseline indicates worsening of severity.
Time to Recovery to Baseline From Last Occurrence of Worst GSRS Score
The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms. A higher score relative to Baseline indicates worsening of severity.
Average Change From Baseline in GSRS Scores to the End of Weeks 4, 6, 8, 10, 12, and 14
Average change from baseline to end of DMF treatment in the GSRS. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms.

Full Information

First Posted
April 23, 2015
Last Updated
March 27, 2017
Sponsor
Biogen
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1. Study Identification

Unique Protocol Identification Number
NCT02428231
Brief Title
Tecfidera Slow-Titration Study
Acronym
TITRATION
Official Title
A Multicenter, Treatment-Blind Phase 3b Study to Evaluate Whether 6-Week Up-Titration in Tecfidera® Dose is Effective in Reducing the Incidence of Gastrointestinal Adverse Events in Patients With Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision
Study Start Date
April 2015 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
January 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
The primary objective of the study is to assess whether a 6-week titration (compared with a 1-week titration) is effective in reducing the incidence of dimethyl fumarate (DMF [Tecfidera])-related gastrointestinal (GI) adverse events (AEs) in participants with multiple sclerosis (MS). The secondary objective of this study is to assess whether a 6-week titration (compared with a 1-week titration) is effective in reducing the average severity and duration of GI symptoms over 12 weeks of DMF treatment in this study population.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
62 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard Treatment (One-Week Titration)
Arm Type
Active Comparator
Arm Description
120 mg DMF twice daily for 1 week, then 240 mg (as 2 120-mg capsules) DMF twice daily for 11 weeks
Arm Title
Slow Up-Titration (Six-Week Titration)
Arm Type
Experimental
Arm Description
120 mg DMF once daily (morning dose) and placebo once daily (evening dose) for 2 weeks, then 120 mg DMF twice daily for 2 weeks, then 240 mg (as 2 120-mg capsules) DMF in the morning and 120 mg in the evening for 2 weeks, then 240 mg (as 2 120-mg capsules) DMF twice daily for 6 weeks
Intervention Type
Drug
Intervention Name(s)
dimethyl fumarate
Other Intervention Name(s)
DMF, Tecfidera, BG00012
Intervention Description
Participants will be dosed twice daily for 12 weeks.
Primary Outcome Measure Information:
Title
Proportion of Participants With a Worsening in Severity of Gastrointestinal (GI) Adverse Events (AEs) on the Gastrointestinal Symptom Rating Scale (GSRS)
Description
The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms. A higher score relative to Baseline indicates worsening of severity.
Time Frame
from Week 2 (Baseline) to Week 14
Secondary Outcome Measure Information:
Title
Average Change From Baseline in GSRS Scores During DMF Treatment
Description
Average change from baseline in GSRS scores over the 12 weeks of DMF treatment as measured by the total change in GSRS scores from baseline divided by the total number of days with GSRS scores recorded. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms.
Time Frame
Week 2 (Baseline), Week 14
Title
Time to First Worsening From Baseline in GSRS Score
Description
The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms. A higher score relative to Baseline indicates worsening of severity.
Time Frame
Week 2 (Baseline), Week 14
Title
Time to Recovery to Baseline From Last Occurrence of Worst GSRS Score
Description
The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms. A higher score relative to Baseline indicates worsening of severity.
Time Frame
Week 2 (Baseline), Week 14
Title
Average Change From Baseline in GSRS Scores to the End of Weeks 4, 6, 8, 10, 12, and 14
Description
Average change from baseline to end of DMF treatment in the GSRS. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms.
Time Frame
Week 2 (Baseline), Weeks 4, 6, 8, 10, 12, 14

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Diagnosis of MS consistent with locally labeled indication for DMF No prior treatment with DMF Female subjects of childbearing potential who are not surgically sterile and male subjects must practice effective contraception during their participation in the study Have had a recent complete blood count (CBC), including lymphocyte count, that does not preclude participation in the study, in the judgement of the investigator Key Exclusion Criteria: Have a recent history or ongoing GI illness (e.g., peptic ulcer, irritable bowel syndrome) or any other current condition with GI signs and symptoms (e.g., nausea, vomiting, abdominal pain, or diarrhea) that may interfere with assessment of study endpoints Have other major comorbid conditions that preclude participation in the study, as determined by the investigator Participant is pregnant, breastfeeding, or planning a pregnancy during the study period Are receiving concomitant disease-modifying therapies for MS including, but not limited to, natalizumab, interferon beta, glatiramer acetate, fingolimod, alemtuzumab, teriflunomide, or laquinimod at screening History of severe allergic or anaphylactic reactions or known drug hypersensitivity 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
Country
United States
Facility Name
Research Site
City
Phoenix
State/Province
Arizona
Country
United States
Facility Name
Research Site
City
Long Beach
State/Province
California
Country
United States
Facility Name
Research Site
City
Miami
State/Province
Florida
Country
United States
Facility Name
Research Site
City
Avon
State/Province
Indiana
Country
United States
Facility Name
Research Site
City
Franklin
State/Province
Indiana
Country
United States
Facility Name
Research Site
City
Overland Park
State/Province
Kansas
Country
United States
Facility Name
Research Site
City
Lewiston
State/Province
Maine
Country
United States
Facility Name
Research Site
City
Asheville
State/Province
North Carolina
Country
United States
Facility Name
Research Site
City
Cary
State/Province
North Carolina
Country
United States
Facility Name
Research Site
City
Charlotte
State/Province
North Carolina
Country
United States
Facility Name
Research Site
City
Wilmington
State/Province
North Carolina
Country
United States
Facility Name
Research Site
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
Research Site
City
Dallas
State/Province
Texas
Country
United States
Facility Name
Research Site
City
Wenatchee
State/Province
Washington
Country
United States
Facility Name
Research Site
City
Leuven
Country
Belgium
Facility Name
Research Site
City
Wilrijk
Country
Belgium
Facility Name
Research Site
City
Prague
Country
Czech Republic
Facility Name
Research Site
City
Merano
State/Province
Bolzano
Country
Italy
Facility Name
Research Site
City
Montichiari
Country
Italy

12. IPD Sharing Statement

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Tecfidera Slow-Titration Study

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