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Completed

NCT Number: NCT02090413

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

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.

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Key information

Conditions

Relapsing-Remitting Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Flushing Immune System Diseases Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting Nervous System Diseases Pathological Conditions, Signs and Symptoms Signs and Symptoms Skin Manifestations

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Research Site, Cork, Ireland

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

dimethyl fumarate

Drug

Other names: BG00012, Tecfidera, DMF

acetylsalicylic acid

Drug

enteric-coated capsule

Other names: ASA, aspirin

ASA-Placebo

Drug

matched placebo

Other names: placebo

Primary outcomes

  1. 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.

  2. 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).

  3. 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.

  4. 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

  1. 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

    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).

  2. 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

    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).

  3. 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 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).

  4. 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

    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).

  5. 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 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).

  6. 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

    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.

  7. Number of Participants With Self-Reported Flushing Events During Weeks 13 to 48

    Time frame: Week 13 to Week 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.

  8. 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

    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.

  9. 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

    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.

  10. 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

    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.

  11. 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

    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.

  12. 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)

    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).

  13. 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

    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).

  14. 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

    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.

  15. 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

    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.

  16. 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

    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.

  17. 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

    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.

  18. 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

    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.

  19. 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

    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."

Sponsors and collaborators

Lead sponsor

Biogen

Industry

Registry information

Official study 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

Acronym: ASSURE

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
Mar 18, 2014
Registry last updated
Dec 28, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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