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
Overview
- Phase
- Phase 3
- Intervention
- dimethyl fumarate
- Conditions
- Multiple Sclerosis
- Sponsor
- Biogen
- Enrollment
- 62
- Locations
- 1
- Primary Endpoint
- Proportion of Participants With a Worsening in Severity of Gastrointestinal (GI) Adverse Events (AEs) on the Gastrointestinal Symptom Rating Scale (GSRS)
- Status
- Terminated
- Last Updated
- 8 years ago
Overview
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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
Standard Treatment (One-Week Titration)
120 mg DMF twice daily for 1 week, then 240 mg (as 2 120-mg capsules) DMF twice daily for 11 weeks
Intervention: dimethyl fumarate
Slow Up-Titration (Six-Week Titration)
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: dimethyl fumarate
Outcomes
Primary Outcomes
Proportion of Participants With a Worsening in Severity of Gastrointestinal (GI) Adverse Events (AEs) on the Gastrointestinal Symptom Rating Scale (GSRS)
Time Frame: from Week 2 (Baseline) to Week 14
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 Outcomes
- Average Change From Baseline in GSRS Scores to the End of Weeks 4, 6, 8, 10, 12, and 14(Week 2 (Baseline), Weeks 4, 6, 8, 10, 12, 14)
- Average Change From Baseline in GSRS Scores During DMF Treatment(Week 2 (Baseline), Week 14)
- Time to First Worsening From Baseline in GSRS Score(Week 2 (Baseline), Week 14)
- Time to Recovery to Baseline From Last Occurrence of Worst GSRS Score(Week 2 (Baseline), Week 14)