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

Relapsing-Remitting Multiple Sclerosis Clinical Trial

— ASSURE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02090413
• Other study ID #: 109MS406
• Secondary ID: 2013-001895-40
• Status: Completed
• Phase: Phase 4
• First received: March 14, 2014
• Last updated: July 25, 2016
• Start date: May 2014
• Est. completion date: November 2015

Study information

• Verified date: July 2016
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Ireland: Irish Medicines BoardUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study is to evaluate whether 150 mg enteric-coated aspirin (acetyl salicylic acid [ASA]) taken twice a day (BID) with DMF (dimethyl fumarate) 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.

Description:

There are two parts to this study: Double-Blind Period from randomization through Week 12; Safety Extension Period from Week 13 to Week 48

Recruitment information / eligibility

• Status: Completed
• Enrollment: 241
• Est. completion date: November 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 able 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 enrolment 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Flushing
• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing-Remitting Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• dimethyl fumarate
Administered as specified in the treatment arm
• acetylsalicylic acid
Administered as specified in the treatment arm
• ASA-Placebo
Matched placebo

Locations

Country	Name	City	State
Ireland	Research Site	Dublin
Ireland	Research Site	Dublin
United Kingdom	Research Site	Basingstoke
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Exeter
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Newcastle upon Tyne
United Kingdom	Research Site	Norwich
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Plymouth
United Kingdom	Research Site	Salford
United Kingdom	Research Site	Swansea

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of 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 to Week 4	No
Primary	Incidence of participant-reported flushing events during the first 4 weeks 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 has been administered and should 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).	Day 1 to Week 4	No
Primary	Severity of participant-reported flushing events during the first 4 weeks of treatment recorded on the eDiary as assessed by MGFSS		Day 1 to Week 4	No
Primary	Severity of participant-reported flushing events during the first 4 weeks of treatment recorded on the eDiary as assessed by MFSS		Day 1 to Week 4	No
Secondary	Incidence of participant-reported flushing events during weeks 5-8 and weeks 9-12 of the study recorded on the eDiary as assessed by MGFSS		Week 5 to Week 12	No
Secondary	Incidence of participant-reported flushing events during weeks 5-8 and weeks 9-12 of the study recorded on the eDiary as assessed by MFSS		Week 5 to Week 12	No
Secondary	Severity of participant-reported flushing events during weeks 5-8 and weeks 9-12 of the study recorded on the eDiary as assessed by MGFSS		Week 5 to Week 12	No
Secondary	Severity of participant-reported flushing events during weeks 5-8 and weeks 9-12 of the study recorded on the eDiary as assessed by MFSS		Week 5 to Week 12	No
Secondary	Duration of participant-reported flushing events during weeks 1-4, 5-8 and 9-12 of the study recorded on the eDiary as assessed by MGFSS		Day 1 to Week 12	No
Secondary	Duration of participant-reported flushing events during weeks 1-4, 5-8 and 9-12 of the study recorded on the eDiary as assessed by MFSS		Day 1 to Week 12	No
Secondary	Incidence of participant-reported flushing events recorded in the paper diary during the safety extension period as assessed by MGFSS		Week 13 to Week 48	Yes
Secondary	Incidence of participant-reported flushing events recorded in the paper diary during the safety extension period as assessed by MFSS		Week 13 to Week 48	Yes
Secondary	Incidence of treatment discontinuation and study withdrawal due to any adverse event (AE)		Day 1 to Week 48	Yes
Secondary	Incidence of treatment discontinuation and study withdrawal due to flushing events		Day 1 to Week 48	Yes
Secondary	Number of participants experiencing treatment-emergent AEs		Day 1 to Week 48	Yes
Secondary	Number of participants experiencing serious adverse events (SAEs)		Day 1 to Week 48	Yes
Secondary	Change from baseline to week 24 and week 48 in quality of life measurements as assessed by SF-36 questionnaire	SF-36 is a self-administered, generic health status questionnaire consisting of 36 questions that measure 8 health concepts: physical functioning, role limitations due to physical problems, bodily pain, general health perception, vitality, social functioning, role limitations due to emotional problems and mental health.	Day 1 to Week 48	No
Secondary	Change from baseline to week 24 and week 48 in quality of life measurements as assessed by the EQ-5D-5L questionnaire	The EQ-5D-3L is a standardized instrument for use as a measure of health outcome. It is a health questionnaire that consists of 2 pages - the EQ-5D descriptive system (page 2) and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, extreme problems.	Day 1 to Week 48	No