Phase 4 Study of Effect of Aspirin on Flushing in Dimethyl Fumarate-Treated Participants With Relapsing-Remitting Multiple Sclerosis (ASSURE)

Biogen

Status and phase: Completed; Phase 4

Conditions: Relapsing-Remitting Multiple Sclerosis

Treatments: Drug: ASA-Placebo; Drug: acetylsalicylic acid; Drug: dimethyl fumarate

Study type: Interventional

Funder types: Industry

Identifiers

NCT02090413

109MS406

2013-001895-40 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 241 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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

Key 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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241 participants in 3 patient groups

DMF + ASA 150 mg BID

Experimental group

Description:

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.)

Treatment:

Drug: acetylsalicylic acid

Drug: dimethyl fumarate

DMF + ASA 75 mg QAM

Experimental group

Description:

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.)

Treatment:

Drug: acetylsalicylic acid

Drug: dimethyl fumarate

Drug: ASA-Placebo

DMF + ASA-Placebo BID

Experimental group

Description:

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.)

Treatment:

Drug: dimethyl fumarate

Drug: ASA-Placebo