A study to evaluate the effect of aspirin on flushing in patients with RRMS treated with Tecfidera

• Register: EUCTR
• Last refreshed on: 18 January 2016
• Main ID: EUCTR2013-001895-40-IE
• Date of registration: 06/03/2014
• Prospective Registration: Yes
• Primary sponsor: Biogen Idec Research Limited
• Public title: A study to evaluate the effect of aspirin on flushing in patients with RRMS treated with Tecfidera
• Scientific 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 (ASSURE) - ASSURE
• Date of first enrolment: 02/05/2014
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001895-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Ireland, United Kingdom

Contacts

• Name: Clinical Trials - Neurology
• Affiliation: Biogen Idec Research Limited

• Name: Clinical Trials - Neurology
• Affiliation: Biogen Idec Research Limited

Key inclusion & exclusion criteria

Inclusion criteria:
To be eligible to participate in this study, candidates must meet the following eligibility criteria at the Screening/Baseline Visit or at the time point specified in the individual eligibility criterion listed:

1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent in accordance with national and local subject privacy regulations.
2. Age =18 years at the time of informed consent.
3. Naïve to fumaric acid esters (e.g., DMF, Fumaderm®, compounded fumarates).
4. Diagnosed with RRMS and satisfies the approved therapeutic indication for DMF.
5. Subjects of childbearing potential must practice effective contraception and be willing and able to continue contraception during the study through at least the Week 12 Visit. For further details of contraceptive requirements for this study.
6. Ability to complete the tolerability scales accurately using the eDiary and ability to complete the paper Flushing Diaries.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 220
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
Candidates will be excluded from study entry if any of the following exclusion criteria exist at the Screening/Baseline Visit or at the time point specified in the individual criterion listed:

1. Inability or unwillingness to comply with study requirements or, at the discretion of the Investigator, is deemed unsuitable for study participation.
2. 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.
3. Known active malignancies (subjects with cutaneous basal cell carcinoma that has been completely excised prior to study entry remain eligible).
4. Chronic use (=7 consecutive days) of ASA- or NSAID-containing products within the month prior to enrolment in the study.
5. A known intolerance to ASA.
6. Active peptic ulceration or a history of peptic ulceration, hemophilia or other clotting disorders, or gout.
7. Known hypersensitivity reactions (e.g., bronchospasm, rhinitis, urticaria) in response to ASA or NSAID administration.
8. Impaired hepatic or renal function, in the opinion of the Investigator.
9. Female subject is pregnant, lactating, or will be attempting to become pregnant during the Double-Blind Period of the study.
10. Currently participating in another interventional clinical trial.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Relapsing-Remitting Multiple Sclerosis
MedDRA version: 16.1 Level: SOC Classification code 10029205 Term: Nervous system disorders System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 16.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: Tecfidera
Product Name: Tecfidera
Product Code: BG00012
Pharmaceutical Form: Gastro-resistant capsule, hard
INN or Proposed INN: DIMETHYL FUMARATE
CAS Number: 624-49-7
Current Sponsor code: BG00012
Other descriptive name: DIMETHYL FUMARATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 120-

Trade Name: Tecfidera
Product Name: Tecfidera
Product Code: BG00012
Pharmaceutical Form: Gastro-resistant capsule, hard
INN or Proposed INN: DIMETHYL FUMARATE
CAS Number: 624-49-7
Current Sponsor code: BG00012
Other descriptive name: DIMETHYL FUMARATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 240-

Trade Name: Micropirin
Pharmaceutical Form: Capsule
INN or Proposed INN: ACETYLSALICYLIC ACID
CAS Number: 50-78-2
Other descriptive name: ASA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: The secondary objectives of this study in this study population are:

1. To evaluate the safety and tolerability of DMF administered with and without enteric-coated ASA in the clinical practice setting.

2. 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.

Primary end point(s): The primary endpoints are as follows:

1. The incidence of subject-reported flushing events based on the Modified Global Flushing Severity Scale (MGFSS) and Modified Flushing Severity Scale (MFSS) data recorded on the hand-held subject reporting device (eDiary) during the first 4 weeks of the study

2. The severity of subject-reported flushing events based on the MGFSS and MFSS data recorded on the eDiary during the first 4 weeks of the study

Main Objective: The primary objective of the study is to evaluate whether 150 mg enteric-coated ASA taken BID with 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 RRMS compared with ASA-placebo administered with DMF in the clinical practice setting.

Timepoint(s) of evaluation of this end point: The first 4 weeks of the study

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. During Weeks 5 through 8 and Weeks 9 through 12 of the study
2. During Week 5 through 8 and Weeks 9 through 12 of the study
3. During Weeks 1 through 4, Weeks 5 through 8, and Weeks 9 through 12 of the study
4. During Weeks 13 through 48 of the study
5. When the subject withdraws from treatment/the study, or at week 48
6. When the subject withdraws from treatment/the study, or at week 48
7. When the subject withdraws from treatment/the study, or at week 48
8. At week 48
9. Week 24 and then Week 48

Secondary end point(s): The secondary endpoints are as follows:
1. Overall incidence of subject-reported flushing events during Weeks 5 through 8 and Weeks 9 through 12 of the study using MGFSS and MFSS data recorded on the eDiary
2. Severity of subject-reported flushing events during Week 5 through 8 and Weeks 9 through 12 of the study using MGFSS and MFSS data recorded on the eDiary
3. Duration of subject-reported flushing events during Weeks 1 through 4, Weeks 5 through 8, and Weeks 9 through 12 of the study based on the MGFSS and MFSS data recorded on the eDiary
4. Overall incidence of subject-reported flushing events using data obtained from the paper Flushing Diaries during Weeks 13 through 48 of the study
5. Incidence of treatment discontinuation and study withdrawal due to any AE
6. Incidence of treatment discontinuation and study withdrawal due to flushing events
7. Incidence of treatment-emergent AEs (excluding nonserious flushing events or flushing events that lead to treatment discontinuation or study withdrawal)
8. Incidence of SAEs
9. Change from Baseline to Week 24 and Week 48 in SF-36 and EQ-5D-5L assessments (quality-of-life measurements)

Secondary ID(s)

109MS406

Source(s) of Monetary Support

Biogen Idec Research Limited