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

• Register: EUCTR
• Last refreshed on: 30 April 2018
• Main ID: EUCTR2014-004562-22-BE
• Date of registration: 09/04/2015
• Prospective Registration: Yes
• Primary sponsor: Biogen Idec Research Limited
• Public title: 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
• Scientific 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
• Date of first enrolment: 10/06/2015
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004562-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: slower dose titration vs. the standard dose titration Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, Czech Republic, France, Germany, Hungary, Italy, Spain, United States

Contacts

• Name: n/a
• Affiliation: Biogen Idec Research Limited

• Name: n/a
• Affiliation: Biogen Idec Research Limited

Key inclusion & exclusion criteria

Inclusion criteria:
To be eligible to participate in this study, candidates must meet the following eligibility criteria at the baseline visit:
1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations
2. Aged 18 to 65 years old, inclusive, at the time of informed consent
3. Diagnosis of MS consistent with locally labeled indication for BG00012
4. No prior treatment with BG00012
5. Female subjects of childbearing potential who are not surgically sterile must practice effective contraception (see Section 15.5.3) during their participation in the study
6. Have had a recent (i.e., at screening or within the previous 6 months) complete blood count (CBC), including lymphocyte count, that does not preclude the subject’s participation in the study, in the judgment of the Investigator
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 285
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion criteria:
Candidates will be excluded from study entry if any of the following exclusion criteria exist at the baseline visit, unless specified otherwise:
1. Are unwilling or unable to comply with study requirements, or are deemed unsuitable for study participation as determined by the Investigator
2. Have a recent history or ongoing GI illness (e.g., peptic ulcer, irritable bowl 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, as determined by the Investigator
3. Have other major comorbid conditions that preclude participation in the study, as determined by the Investigator
4. Subject is pregnant, breastfeeding, or planning a pregnancy during the study period
5. Are receiving concomitant disease-modifying therapies for MS including, but not limited to, natalizumab, IFN-ß, glatiramer acetate, fingolimod, alemtuzumab, teriflunomide, or laquinimod at screening
6. History of severe allergic or anaphylactic reactions or known drug hypersensitivity
7. Current enrollment in any clinical study or Biogen Idec-sponsored study or other studies that may conflict with this study (e.g., health economics studies or local registries)



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Multiple Sclerosis
MedDRA version: 17.1 Level: SOC Classification code 10029205 Term: Nervous system disorders System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 17.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: BG00012
Product Code: BG00012
Pharmaceutical Form: Gastro-resistant capsule, hard
INN or Proposed INN: DIMETHYL FUMARATE
CAS Number: 624-49-7
Current Sponsor code: BG00012
Other descriptive name: DIMETHYL FUMARATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 120-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: 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 BG00012 treatment in this study population.

Main Objective: 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 BG00012-related GI AEs in subjects with MS.

Primary end point(s): The primary endpoint is the proportion of subjects with a worsening in severity of GI AEs, defined as a positive average change from baseline to the end of BG00012 treatment in the Gastrointestinal Symptom Rating Scale (GSRS).

Timepoint(s) of evaluation of this end point: Subjects will be required to record their GI symptoms in the eDiary every day from the baseline visit until the end of the 12-week BG00012 treatment period (Week 14). Timepoint for evaluation of the change in GSRS score from baseline will be Week 14.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Timepoint for evaluation of:
1. Timepoint for evaluation of the change in GSRS score from baseline will be Week 14.
2 and 3. will be evaluated as they occur.
4. Timepoint for evaluation will be Weeks 4, 6, 8, 10, 12, and 14

Secondary end point(s): The secondary endpoints are as follows:
1. Average change from baseline in GSRS scores over the 12 weeks of BG00012 treatment as measured by the total change in GSRS scores from baseline divided by the total number of days with GSRS scores recorded
2. Time to first worsening in GSRS score from baseline
3. Time to recovery to baseline score from the last occurrence of worst GSRS score
4. Average change from baseline in GSRS scores to the end of Weeks 4, 6, 8, 10, 12, and 14

Secondary ID(s)

109MS416

Source(s) of Monetary Support

Biogen Idec Research Limited