A Phase 4, Randomized, Double-Blind Study With a Safety Extension Period to Evaluate the Effect of Aspirin on Flushing Events in Subjects With Relapsing-Remitting Multiple Sclerosis Treated With Tecfidera® (Dimethyl Fumarate) Delayed-Release Capsules
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Biogen
- Enrollment
- 241
- Locations
- 1
- Primary Endpoint
- Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS)
Study Overview
Brief Summary
The primary objective of the study is to evaluate whether 150 mg enteric-coated aspirin (acetylsalicylic acid [ASA]) taken twice a day (BID) with dimethyl fumarate (DMF) administration or 75 mg enteric-coated ASA taken once daily in the morning (QAM) with DMF administration reduces the incidence and/or severity of flushing events in subjects with relapsing-remitting multiple sclerosis (RRMS) compared with ASA-placebo administered with DMF in the clinical practice setting.
Secondary objectives of this study are: to evaluate the safety and tolerability of DMF administered with and without enteric-coated ASA in the clinical practice setting; to evaluate the impact of DMF administration on quality of life as measured by the Short Form 36 (SF-36®) and European Quality of Life - 5 Dimensions - 5 Levels (EQ-5D-5L) questionnaires.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Naïve to fumaric acid esters (e.g. DMF, Fumaderm, compounded fumarates)
- •Diagnosed with RRMS and satisfies the approved therapeutic indication for DMF
- •Participants of childbearing potential must practice effective contraception and be willing and able to continue contraception throughout the study
- •Ability to complete the tolerability scales accurately using the electronic diary (eDiary) and ability to complete the paper Flushing Diaries
Exclusion Criteria
- •Inability or unwillingness to comply with study requirements or, at the discretion of the Investigator, is deemed unsuitable for study participation
- •One or more major comorbidities that, in the opinion of the Investigator, may affect the outcome of the study or otherwise makes the subject an unsuitable candidate for study participation. The prevailing product labels for both DMF and ASA should be used as guides
- •Known active malignancies (subjects with cutaneous basal cell carcinoma that has been completely excised prior to study entry remain eligible)
- •Chronic use (≥7 consecutive days) of ASA- or nonsteroidal anti-inflammatory drugs (NSAID)-containing products within the month prior to enrollment in the study
- •A known intolerance to ASA
- •Active peptic ulceration or a history of peptic ulceration, hemophilia or other clotting disorders, or gout
- •Known hypersensitivity reactions (e.g., bronchospasm, rhinitis, urticaria) in response to ASA or NSAID administration
- •Impaired hepatic or renal function, in the opinion of the investigator
- •Female subject is pregnant, lactating, or will be attempting to become pregnant during the Double-Blind Period (first 12 weeks) of the study
- •Currently participating in another interventional clinical trial
- •NOTE: Other protocol-defined inclusion/exclusion criteria may apply
Arms & Interventions
DMF + ASA 150 mg BID
DMF 120 mg taken BID for the first 7 days and 240 mg BID from Week 2 through Week 48.
ASA 150 mg is taken BID from Day 1 through Week 4. (Between Weeks 5 and 8, ASA is prohibited; between Weeks 9 and 48, ASA is allowed as needed.)
Intervention: dimethyl fumarate (Drug)
DMF + ASA 150 mg BID
DMF 120 mg taken BID for the first 7 days and 240 mg BID from Week 2 through Week 48.
ASA 150 mg is taken BID from Day 1 through Week 4. (Between Weeks 5 and 8, ASA is prohibited; between Weeks 9 and 48, ASA is allowed as needed.)
Intervention: acetylsalicylic acid (Drug)
DMF + ASA 75 mg QAM
DMF 120 mg taken BID for the first 7 days and 240 mg BID from Week 2 through Week 48.
ASA 75 mg is taken in the morning (QAM) and ASA-Placebo is taken in the evening (QPM) from Day 1 through Week 4. (Between Weeks 5 and 8, ASA is prohibited; between Weeks 9 and 48, ASA is allowed as needed.)
Intervention: dimethyl fumarate (Drug)
DMF + ASA 75 mg QAM
DMF 120 mg taken BID for the first 7 days and 240 mg BID from Week 2 through Week 48.
ASA 75 mg is taken in the morning (QAM) and ASA-Placebo is taken in the evening (QPM) from Day 1 through Week 4. (Between Weeks 5 and 8, ASA is prohibited; between Weeks 9 and 48, ASA is allowed as needed.)
Intervention: acetylsalicylic acid (Drug)
DMF + ASA 75 mg QAM
DMF 120 mg taken BID for the first 7 days and 240 mg BID from Week 2 through Week 48.
ASA 75 mg is taken in the morning (QAM) and ASA-Placebo is taken in the evening (QPM) from Day 1 through Week 4. (Between Weeks 5 and 8, ASA is prohibited; between Weeks 9 and 48, ASA is allowed as needed.)
Intervention: ASA-Placebo (Drug)
DMF + ASA-Placebo BID
DMF 120 mg taken BID for the first 7 days and 240 mg BID from Week 2 through Week 48.
ASA-Placebo is taken BID from Day 1 through Week 4. (Between Weeks 5 and 8, ASA is prohibited; between Weeks 9 and 48, ASA is allowed as needed.)
Intervention: dimethyl fumarate (Drug)
DMF + ASA-Placebo BID
DMF 120 mg taken BID for the first 7 days and 240 mg BID from Week 2 through Week 48.
ASA-Placebo is taken BID from Day 1 through Week 4. (Between Weeks 5 and 8, ASA is prohibited; between Weeks 9 and 48, ASA is allowed as needed.)
Intervention: ASA-Placebo (Drug)
Outcomes
Primary Outcomes
Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS)
Time Frame: Day 2 to Week 4
Participant-reported flushing events during the first 4 weeks treatment, recorded on the hand-held participant reporting device (eDiary) as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). Day 1 data are not included in the analysis because MGFSS question refers to last 24 hours flushing score.
Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS)
Time Frame: Day 1 to Week 4
Participant-reported flushing events during the first 4 weeks of treatment recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin. This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects).
Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MGFSS
Time Frame: Day 2 to Week 4
Worst severity of participant-reported flushing events during the first 4 weeks of treatment recorded on the eDiary as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). Day 1 data are not included in the analysis because MGFSS question refers to last 24 hours flushing score.
Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS
Time Frame: Day 1 to Week 4
Worst severity of participant-reported flushing events during the first 4 weeks of treatment recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin.This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects).
Secondary Outcomes
- Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MGFSS(Week 5 to Week 12)
- Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS(Week 5 to Week 12)
- Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MGFSS(Week 5 to Week 12)
- Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS(Week 5 to Week 12)
- Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MGFSS(Day 1 to Week 12)
- Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MFSS(Day 1 to Week 12)
- Number of Participants With Self-Reported Flushing Events During Weeks 13 to 48(Week 13 to Week 48)
- Number of Participants Experiencing Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs in the First 12 Weeks(Day 1 to Week 12)
- Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48(Week 13 to Week 48)
- Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-emergent Flushing AEs in the First 12 Weeks(Day 1 to Week 12)
- Number of Participants Discontinuing Treatment and Discontinuing the Study Due to Treatment-Emergent Flushing AEs in Weeks 13 to 48(Week 13 to Week 48)
- Change From Baseline at Weeks 24 and 48 in Quality of Life Measurements as Assessed by Short Form-36 (SF-36) Questionnaire: Physical Component Summary (PCS)(Baseline, Week 24, Week 48 or early termination (ET))
- Change From Baseline at Weeks 24 and 48 in Quality of Life Measurements as Assessed by Short Form-36 (SF-36) Questionnaire: Mental Component Summary (MCS)(Baseline, Week 24, Week 48 or ET)
- Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the European Quality of Life 5-Dimensions Questionnaire (EQ-5D-5L) Questionnaire: Mobility(Baseline, Week 24, Week 48 or ET)
- Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Self-Care(Baseline, Week 24, Week 48 or ET)
- Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Usual Activities(Baseline, Week 24, Week 48 or ET)
- Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Pain/Discomfort(Baseline, Week 24, Week 48 or ET)
- Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-5D-5L Questionnaire: Anxiety/Depression(Baseline, Week 24, Week 48 or ET)
- Change From Baseline to Week 24 and Week 48 in Quality of Life Measurements as Assessed by the EQ-VAS(Baseline, Week 24, Week 48 or ET)