Relapsing-Remitting Multiple SclerosisPhase 4ASSURENCT02090413

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

A Phase 4 study testing dimethyl fumarate and acetylsalicylic acid in people with Relapsing-Remitting Multiple Sclerosis, run by Biogen at 21 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Relapsing-Remitting Multiple Sclerosis
What is being tested?: dimethyl fumarate and acetylsalicylic acid
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 241 participants
Where: 21 sitesin 2 countries
Study dates: May 2014to Nov 2015
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

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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 locations and contacts

21 sites in 2 countries.

Country

City, postcode or hospital

21 sites in 2 countries

United Kingdom17 sites

Research Site
Basingstoke, RG24 9NA
Research Site
Birmingham, B15 2TH
Research Site
Cardiff, CF14 4XW
Research Site
Edinburgh, EHA 2XU
Research Site
Exeter, EX2 5DW
Research Site
Glasgow, G51 4TH
Research Site
Leicester, LE5 4PW
Research Site
Liverpool, L9 7LJ
Research Site
London, SE5 9RS
Research Site
London, SW17 0QT
Research Site
London, WC1N 3BG
Research Site
Newcastle upon Tyne, NE1 4LP
Research Site
Norwich, NR4 7UY
Research Site
Nottingham, NG7 2UH
Research Site
Plymouth, PL6 8BX
Research Site
Salford, M6 8HD
Research Site
Swansea, SA6 6NL

Other trials in United Kingdom

Ireland4 sites

Research Site
Cork
Research Site
Dublin, Dublin 4
Research Site
Dublin, Dublin 7
Research Site
Dublin, Dublin 9

Other trials in Ireland

About this study

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

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.

Conditions: Relapsing-Remitting Multiple Sclerosis
Being tested: dimethyl fumarate, acetylsalicylic acid, ASA-Placebo
Keywords: multiple sclerosis, flushing, aspirin
Medical subject headings: Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Flushing

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

dimethyl fumarateDrug
Also called BG00012, Tecfidera, DMF
acetylsalicylic acidDrug
Also called ASA, aspirin
enteric-coated capsule
ASA-PlaceboDrug
Also called placebo
matched placebo

Study groups in NCT02090413
Study group	Role	What they receive
DMF + ASA 150 mg BID	Experimental	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.) Receives: Drug: dimethyl fumarate; Drug: acetylsalicylic acid
DMF + ASA 75 mg QAM	Experimental	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.) Receives: Drug: dimethyl fumarate; Drug: acetylsalicylic acid; Drug: ASA-Placebo
DMF + ASA-Placebo BID	Experimental	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.) Receives: Drug: dimethyl fumarate; Drug: ASA-Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS)
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.
Measured: Day 2 to Week 4
Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS)
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).
Measured: Day 1 to Week 4
Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MGFSS
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.
Measured: Day 2 to Week 4
Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS
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).
Measured: Day 1 to Week 4

Secondary outcomes (19)

Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MGFSS
Participant-reported flushing events during Weeks 5-8 and Weeks 9-12 of the study 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).
Measured: 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
Participant-reported flushing events during Weeks 5-8 and Weeks 9-12 of the study 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).
Measured: 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
Worst 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. 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).
Measured: 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
Worst 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. 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).
Measured: 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
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. 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).
Measured: 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
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. 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). For participants with more than 1 flushing event during a visit interval, the average duration for the visit interval was used.
Measured: Day 1 to Week 12
Number of Participants With Self-Reported Flushing Events During Weeks 13 to 48
Participant-reported flushing events (which include redness, warmth, tingling, and/or itching of the skin) during Weeks 13 to 48 of treatment were recorded in the CRF.
Measured: 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
AE: any untoward medical occurrence that does not necessarily have a causal relationship with treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity, or; results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above. A treatment-emergent AE is defined as any AE that occurs after the first administration of DMF or ASA/Placebo drug.
Measured: Day 1 to Week 12
Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48
AE: any untoward medical occurrence that does not necessarily have a causal relationship with treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity, or; results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above. A treatment-emergent AE is defined as any AE that occurs after the first administration of DMF or ASA/Placebo drug.
Measured: 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
A treatment-emergent AE is defined as any AE that occurs after the first administration of DMF or ASA/Placebo drug. Flushing AEs include redness, warmth, tingling, and/or itching of the skin.
Measured: 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
A treatment-emergent AE is defined as any AE that occurs after the first administration of DMF or ASA/Placebo drug. Flushing AEs include redness, warmth, tingling, and/or itching of the skin.
Measured: 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)
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. The score for a domain is an average of the individual question scores, which are scaled 0 (worst health-related quality of life) to 100 (best health-related quality of life). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0 (lowest level of physical functioning) to 100 (highest level of physical functioning).
Measured: 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)
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. The score for a domain is an average of the individual question scores, which are scaled 0 (worst health-related quality of life) to 100 (best health-related quality of life). Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0 (lowest level of physical functioning) to 100 (highest level of physical functioning).
Measured: 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
EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-Visual Analog Scale (EQ-VAS). The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has "no problems" (1), "some problems" (2), or "severe problems" (3). A negative change from Baseline indicates improvement.
Measured: 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
EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-VAS. The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has "no problems" (1), "some problems" (2), or "severe problems" (3). A negative change from Baseline indicates improvement.
Measured: 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
EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-VAS. The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has "no problems" (1), "some problems" (2), or "severe problems" (3). A negative change from Baseline indicates improvement.
Measured: 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
EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-VAS. The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has "no problems" (1), "some problems" (2), or "severe problems" (3). A negative change from Baseline indicates improvement.
Measured: 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
EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-VAS. The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has "no problems" (1), "some problems" (2), or "severe problems" (3). A negative change from Baseline indicates improvement.
Measured: 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
For the EQ-VAS, the participant was instructed to draw a line on a 20-cm vertical scale at the point that best describes his or her own health, where 0 represents the "worst imaginable health state" and 100 represents the "best imaginable health state."
Measured: Baseline, Week 24, Week 48 or ET

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2014Nov 2015

First posted18 Mar 2014 (estimated)
Study startMay 2014
Primary completionFeb 2015
Study completionNov 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Relapsing-Remitting Multiple SclerosisStudies of the same condition, open and under way.
More trials run by BiogenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 241 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02090413
Sponsor's protocol ID: 109MS406
Other IDs: 2013-001895-40
Acronym: ASSURE
Status last verified: Nov 2016
First submitted: 14 Mar 2014
Last updated: 28 Dec 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 28 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02090413
Acronym / sponsor ID: ASSURE / 109MS406
Conditions: Relapsing-Remitting Multiple Sclerosis
Keywords: multiple sclerosis, flushing, aspirin
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 241 participants (actual)
Lead sponsor: BiogenIndustry (pharma, biotech, devices)
Study start: May 2014
Primary completion: Feb 2015 (actual)
Study completion: Nov 2015 (actual)
First posted: 18 Mar 2014 (estimated)
Results: Posted 28 Dec 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
DMF + ASA 150 mg BID	Experimental	Drug: dimethyl fumarate, Drug: acetylsalicylic acidDMF 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.)
DMF + ASA 75 mg QAM	Experimental	Drug: dimethyl fumarate, Drug: acetylsalicylic acid, Drug: ASA-PlaceboDMF 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.)
DMF + ASA-Placebo BID	Experimental	Drug: dimethyl fumarate, Drug: ASA-PlaceboDMF 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.)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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 (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
dimethyl fumarateAlso: BG00012, Tecfidera, DMF	Drug	DMF + ASA 150 mg BID, DMF + ASA 75 mg QAM, DMF + ASA-Placebo BID
acetylsalicylic acidAlso: ASA, aspirinenteric-coated capsule	Drug	DMF + ASA 150 mg BID, DMF + ASA 75 mg QAM
ASA-PlaceboAlso: placebomatched placebo	Drug	DMF + ASA 75 mg QAM, DMF + ASA-Placebo BID

Primary outcome

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).

19 secondary outcomes

Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MGFSS
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day 1 to Week 12
Number of Participants With Self-Reported Flushing Events During Weeks 13 to 48
Time frame: 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
Time frame: Day 1 to Week 12
Number of Participants Experiencing Treatment-Emergent AEs, SAEs, and Discontinuations Due to AEs in Weeks 13 to 48
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline, Week 24, Week 48 or ET

Results and safety

Results posted to the registry on 28 Dec 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
DMF + ASA-Placebo BID	81	62
DMF + ASA 75 mg QAM	80	60
DMF + ASA 150 mg BID	80	57

Primary outcome: 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. Number. Unit: percentage of participants

Measure	DMF + ASA-Placebo BID n = 80	DMF + ASA 75 mg QAM n = 79	DMF + ASA 150 mg BID n = 80
Weeks 1-4 combined; n=80, 79, 80	90.0	92.4	88.8
Week 1; n=80, 77, 80	83.8	85.7	83.8
Week 2; n=77, 76, 79	76.6	61.8	69.6
Week 3; n=74, 74, 76	73.0	55.4	53.9
Week 4; n=72, 71, 71	59.7	54.9	54.9

DMF + ASA-Placebo BID vs DMF + ASA 75 mg QAM: Difference in percentage: 2.4 (95% CI -6.4 to 11.2)
DMF + ASA-Placebo BID vs DMF + ASA 150 mg BID: Difference in percentage: -1.3 (95% CI -10.8 to 8.3)
DMF + ASA-Placebo BID vs DMF + ASA 75 mg QAM: Difference in percentage: 2.0 (95% CI -9.3 to 13.2)

Population analysed: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug); n=number of participants evaluable at given time point.

Primary outcome: 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. Number. Unit: percentage of participants

Measure	DMF + ASA-Placebo BID n = 80	DMF + ASA 75 mg QAM n = 78	DMF + ASA 150 mg BID n = 80
Overall flushing events	91.3	96.2	96.3
Overall redness events	90.0	88.5	88.8
Overall warmth events	92.5	97.4	97.5
Overall tingling events	81.3	87.2	86.3
Overall itching events	87.5	79.5	76.3

DMF + ASA-Placebo BID vs DMF + ASA 75 mg QAM: Difference in percentage: 4.9 (95% CI -2.6 to 12.4)
DMF + ASA-Placebo BID vs DMF + ASA 150 mg BID: Difference in percentage: 5.0 (95% CI -2.5 to 12.5)
DMF + ASA-Placebo BID vs DMF + ASA 75 mg QAM: Difference in percentage: -1.5 (95% CI -11.2 to 8.1)

Population analysed: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).

Primary outcome: Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MGFSS

Time frame: Day 2 to Week 4. Mean (Standard Deviation). Unit: units on a scale

Measure	DMF + ASA-Placebo BID n = 80	DMF + ASA 75 mg QAM n = 79	DMF + ASA 150 mg BID n = 80
Value	4.36 (2.66)	3.99 (2.63)	3.93 (2.47)

Population analysed: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).

Primary outcome: Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS

Time frame: Day 1 to Week 4. Mean (Standard Deviation). Unit: units on a scale

Measure	DMF + ASA-Placebo BID n = 80	DMF + ASA 75 mg QAM n = 78	DMF + ASA 150 mg BID n = 80
Overall flushing	4.84 (2.77)	4.73 (2.43)	4.78 (2.53)
Redness	4.83 (2.69)	4.65 (2.73)	4.34 (2.67)
Warmth	5.03 (2.54)	4.88 (2.38)	4.9 (2.46)
Tingling	3.31 (2.38)	3.62 (2.53)	3.3 (2.30)
Itching	3.7 (2.55)	3.64 (2.76)	3.23 (2.66)

Population analysed: Evaluable participants in the Safety Population (randomized participants who received at least 1 dose of study drug).

19 secondary outcomes are reported in the full results.

Adverse events

Time frame: Screening through Week 48. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
DMF + ASA-Placebo BID	4 of 81 (4.9%)	77 of 81 (95.1%)	Not reported
DMF + ASA 75 mg QAM	8 of 80 (10%)	76 of 80 (95%)	Not reported
DMF + ASA 150 mg BID	5 of 80 (6.3%)	76 of 80 (95%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Biogen

21 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing dimethyl fumarate and acetylsalicylic acid in people with Relapsing-Remitting Multiple Sclerosis, run by Biogen at 21 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United Kingdom, Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02090413.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2016.