Relapsing-Remitting Multiple SclerosisPhase 4PROTECNCT01930708
A Study Evaluating the Effectiveness of Tecfidera (Dimethyl Fumarate) on Multiple Sclerosis (MS) Disease Activity and Patient-Reported Outcomes
A Phase 4 study testing dimethyl fumarate in people with Relapsing-Remitting Multiple Sclerosis and Multiple Sclerosis, run by Biogen at 90 sites in 11 countries.
Trial summary
The primary objective of the study is to estimate the annualized relapse rate (ARR) in participants with Relapsing Remitting Multiple Sclerosis (RRMS) who are treated with dimethyl fumarate (DMF) over a 12-month period. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsing-Remitting Multiple Sclerosis, Multiple Sclerosis
- What is being tested?
- dimethyl fumarate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,114 participants
- Where
- 90 sitesin 11 countries
- Study dates
- 31 Oct 2013to 9 Jan 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- Have a diagnosis of Relapsing-Remitting Multiple Sclerosis (RRMS) and satisfy the approved therapeutic indication for DMF (per the local DMF product information).
- Must be naïve to DMF, Fumaderm®, and other compounded fumarates, and to MS therapies that are primarily prescribed second-line (e.g., natalizumab, fingolimod) and to alemtuzumab.
- Have a recent complete blood count (CBC) that does not preclude the subject's participation in the study, in the judgment of the Investigator.
Who cannot join
- Are unwilling or unable to comply with study requirements, or are deemed unsuitable for study participation as determined by the Investigator.
- Have major comorbid conditions that preclude participation in the study, as determined by the Investigator.
- Are pregnant, unless DMF is clearly needed and the potential benefit of DMF to the subjects justifies the potential risk to the fetus, in the judgment of the Investigator (in all countries except Austria). In Austria, pregnant subjects are excluded from participation in the study.
- Are women of childbearing potential and are not using appropriate contraception (per the local DMF product information) as determined by the Investigator.
- Women who are breastfeeding may be excluded (per the local DMF product information) at the discretion of the Investigator.
- Have previously received or are receiving treatment with MS therapies primarily used second-line (e.g., natalizumab, fingolimod) or alemtuzumab, or are currently receiving and planning to continue on other disease-modifying therapies for RRMS.
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- Are hypersensitive to the active ingredient in the DMF drug product (i.e., DMF) or to any of the excipients listed in the local DMF product information.
- Current enrollment in any clinical trial except for the Biogen Idec DMF Pregnancy Exposure Registry or other studies that, according to the study Medical Director, do not conflict with this study (e.g., health economics studies or local registries).
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
90 sites in 11 countries.
90 sites in 11 countries
France19 sites
Research Site
Besançon, Doubs, 25030
Research Site
Bordeaux, Gironde, 33076
Research Site
Colmar, Haut Rhin, 68024
Research Site
Dijon, Cote dÝOr, 21079
Research Site
Grenoble, Isere, 39043
Research Site
La Roche-sur-Yon, Vendee, 85025
Research Site
Le Chesnay, Yvelines, 78157
Research Site
Lille, Nord, 59020
Research Site
Lille, Nord, 59037
Research Site
Limoges, Haute Vienne, 87042
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Nancy, 54035
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Nantes, Loire Atlantique, 44093
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Nîmes, Gard, 30029
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Poitiers, Vienne, 86021
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Reims, Marne, 51092
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Rennes, Ille Et Vilaine, 35033
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Rouen, 76031
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Strasbourg, Bas Rhin, 67098
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Toulouse, Haute Garonne, 31059
Italy15 sites
Research Site
Ancona, 60126
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Bergamo, 24100
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Bolzano, 39100
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Castelfiorentino, 50051
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Florence, 50139
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Genova, 16153
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Messina, 98121
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Milan, 20133
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Naples, 80131
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Perugia, 06156
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Pozzilli, 86077
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Roma, 00135
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Roma, 00189
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Siena, 53100
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Torino, 10124
Spain11 sites
Research Site
Barcelona, 8035
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Bilbao, 48013
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Córdoba, 14011
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El Palmar, 30120
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Girona, 17007
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Majadahonda, Madrid, 28222
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Málaga, 29010
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Seville, 41009
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Valencia, 46026
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Vigo, 36204
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Zaragoza, 50009
Portugal9 sites
Research Site
Almada, 2801-915
Research Site
Amadora, 2720-276
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Guimarães, 4835-044
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Lisbon, 1169-050
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Lisbon, 1649-035
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Loures, 2674-514
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Porto, 4099-001
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Porto, 4200-319
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Setúbal, 2910-446
Austria8 sites
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Innsbruck, 6020
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Klagenfurt, 9026
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Linz, 4020
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Salzburg, 5020
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Sankt Pölten, 3100
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Vienna, 1090
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Vienna, 1220
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Villach, 9500
Canada8 sites
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Calgary, Alberta, T2N 2T9
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Halifax, Nova Scotia, B3H 3A7
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London, Ontario, N6A 5A5
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Montreal, Quebec, H8A 2B4
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Ottawa, Ontario, K1H 8L6
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Saint John's, New Brunswick, E2K 5S9
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St. John's, Newfoundland and Labrador, A1B 3V6
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Victoria, British Columbia, V8R 1J6
Czechia7 sites
Research Site
Brno, 625 00
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Havířov, 736 00
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Hradec Králové, 500 05
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Olomouc, 775 20
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Pardubice, 532 03
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Prague, 100 34
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Prague, 128 08
Hungary6 sites
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Budapest, 1076
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Budapest, 1083
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Debrecen, 4032
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Pécs, 7623
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Szeged, 6725
Research Site
Veszprém, 8200
Belgium3 sites
Research Site
Bruges, 8000
Research Site
Brussels, 1200
Research Site
Melsbroek, 1820
About this study
Official title: A Multicenter, Open-Label Study Evaluating the Effectiveness of Oral Tecfidera™ (Dimethyl Fumarate) on MS Disease Activity and Patient-Reported Outcomes in Subjects With Relapsing-Remitting Multiple Sclerosis in the Real-World Setting
The primary objective of the study is to estimate the annualized relapse rate (ARR) in participants with Relapsing Remitting Multiple Sclerosis (RRMS) who are treated with dimethyl fumarate (DMF) over a 12-month period.
The secondary objectives of this study in this population are to assess the impact of DMF over a 12-month period on participants -reported health-related quality of life (HRQoL) outcomes, additional clinical effectiveness outcomes, and health economics-related outcomes, and to characterize participants-reported adherence to DMF.
- Being tested
- dimethyl fumarate
- Keywords
- BG-12
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dimethyl fumarateDrug
Also called Tecfidera, DMF, BG00012
Administered as per the approved dosage in all countries where DMF has received marketing authorization.
| Study group | Role | What they receive |
|---|---|---|
| DMF | Experimental | 120 mg capsule oral twice daily (BID) during the first week and 240 mg BID thereafter. Receives: Drug: dimethyl fumarate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annualized Relapse Rate (ARR)
Measured: 12 Months
Secondary outcomes (16)
Change from Baseline in Multiple Sclerosis Impact Scale (MSIS-29) score
This is a validated, 29-item, MS-specific HRQoL scale that measures the physical (20 items) and psychological (9 items) impact of MS on the participant's day-to-day life during the previous 2 weeks. For each item, the subject is asked to circle the number that best describes his or her situation. The numbers for each item range from 1 (not at all) to 5 (extremely).
Measured: 12 Months
Change from Baseline in Modified Fatigue Impact Scale-5 Item (MFIS-5) score
This scale consists of 5 statements that describe how fatigue may affect a person. For each statement, the participant is asked to circle the number that best indicates how often fatigue has affected him or her during the previous 4 weeks. The numbers for each question range from 0 (never) to 4 (almost always).
Measured: 12 Months
Change from Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) score
This is a validated, 14-item questionnaire that measures a participant's level of satisfaction/dissatisfaction with medication.
Measured: 12 Months
Change from Baseline in EQ-5D 5 level version (EQ-5D-5L) index
The widely validated EQ-5D includes 2 components, the EQ-5D descriptive system and the EQ VAS. The EQ-5D 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 subject is instructed to indicate whether he or she has "no problems" (level 1), "slight problems" (level 2), "moderate problems" (level 3), "severe problems (level 4), or "extreme problems/inability" (level 5) on that day. For the EQ VAS, the participant is instructed to mark an "x" on a vertical scale at the point that best describes his or her own health on that day, where 0 represents the "worst health" he or she can imagine and 100 the "best health" he or she can imagine.
Measured: 12 Months
Change from Baseline in participants-Reported Indices for Multiple Sclerosis-Activity Limitations (PRIMUS-Activity Limitations) score
This 15-item component of the PRIMUS assesses a participant's ability to carry out various activities of daily living during the previous week without the use of aids (e.g., cane, walker, or wheelchair) or assistance. For each item, the participant is asked whether he or she can perform the activity without difficulty or with difficulty, or is unable to perform the activity.
Measured: 12 Months
Change from Baseline in Work Productivity and Activity Impairment-Multiple Sclerosis version (WPAI-MS) score
This 6-item instrument assesses employment status, and, during the previous 7 days, hours of missed work due to MS or other reasons, hours worked (if employed), effect on productivity due to MS while working, and activity impairment attributable to health problems.
Measured: 12 Months
Change from Baseline in Beck Depression Inventory-Fast Screen (BDI-Fast Screen) score
This is a 7-item scale that evaluates depression in participants with medical illness during the prior 2 weeks. It has been validated in subjects with MS.
Measured: 12 Months
Proportion of participants with confirmed (24-week) Expanded Disability Status Scale (EDSS) progression
The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist.
Measured: 12 Months
Annualized Relapse Rate (ARR) at Baseline (i.e., over the 12 months prior to enrollment) and at Month 6
Measured: Baseline, 6 Months
The proportion of participants relapsed
Measured: 12 Months
Number of participants who are hospitalized/have emergency room visits due to MS relapses or have relapses requiring intravenous (IV) steroid treatment during the study, or who make visits to neurologists/other specialists due to MS
Measured: 12 Months
Proportion of participants who are hospitalized/have emergency room visits due to MS relapses or have relapses requiring intravenous (IV) steroid treatment during the study, or who make visits to neurologists/other specialists due to MS
Measured: 12 Months
Proportion of participants who report taking the prescribed DMF dose
Measured: 12 Months
Percentage of participants who report taking the prescribed DMF dose
Measured: 12 Months
Reasons reported by participants for not taking prescribed DMF dose
Measured: 12 Months
Change from baseline in EQ Visual Analog Scale (EQVAS) score
A component of the EQ-5D, where participants are asked to rate their overall health-related quality of life on a standard vertical 20 cm visual analogue scale (similar to a thermometer) between 100 (best health imaginable) and 0 (worst health imaginable).
Measured: 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2013 (estimated)
- Study start31 Oct 2013
- Primary completion31 Mar 2016
- Study completion9 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1,114 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01930708
- Sponsor's protocol ID
- 109MS408
- Other IDs
- 2013-001656-35
- Acronym
- PROTEC
- Status last verified
- Mar 2020
- First submitted
- 15 Aug 2013
- Last updated
- 19 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Berger T, Brochet B, Brambilla L, Giacomini PS, Montalban X, Vasco Salgado A, Su R, Bretagne A. Effectiveness of delayed-release dimethyl fumarate on patient-reported outcomes and clinical measures in patients with relapsing-remitting multiple sclerosis in a real-world clinical setting: PROTEC. Mult Scler J Exp Transl Clin. 2019 Dec 2;5(4):2055217319887191. doi: 10.1177/2055217319887191. eCollection 2019 Oct-Dec.
PubMed 31832225
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-Label Study Evaluating the Effectiveness of Oral Tecfidera™ (Dimethyl Fumarate) on MS Disease Activity and Patient-Reported Outcomes in Subjects With Relapsing-Remitting Multiple Sclerosis in the Real-World Setting
- ClinicalTrials.gov ID
- NCT01930708
- Acronym / sponsor ID
- PROTEC / 109MS408
- Keywords
- BG-12
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,114 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- 31 Oct 2013 (actual)
- Primary completion
- 31 Mar 2016 (actual)
- Study completion
- 9 Jan 2020 (actual)
- First posted
- 29 Aug 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of the study is to estimate the annualized relapse rate (ARR) in participants with Relapsing Remitting Multiple Sclerosis (RRMS) who are treated with dimethyl fumarate (DMF) over a 12-month period.
The secondary objectives of this study in this population are to assess the impact of DMF over a 12-month period on participants -reported health-related quality of life (HRQoL) outcomes, additional clinical effectiveness outcomes, and health economics-related outcomes, and to characterize participants-reported adherence to DMF.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DMF | Experimental | Drug: dimethyl fumarate120 mg capsule oral twice daily (BID) during the first week and 240 mg BID thereafter. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Have a diagnosis of Relapsing-Remitting Multiple Sclerosis (RRMS) and satisfy the approved therapeutic indication for DMF (per the local DMF product information).
- Must be naïve to DMF, Fumaderm®, and other compounded fumarates, and to MS therapies that are primarily prescribed second-line (e.g., natalizumab, fingolimod) and to alemtuzumab.
- Have a recent complete blood count (CBC) that does not preclude the subject's participation in the study, in the judgment of the Investigator.
Key exclusion criteria (9 listed)
- Are unwilling or unable to comply with study requirements, or are deemed unsuitable for study participation as determined by the Investigator.
- Have major comorbid conditions that preclude participation in the study, as determined by the Investigator.
- Are pregnant, unless DMF is clearly needed and the potential benefit of DMF to the subjects justifies the potential risk to the fetus, in the judgment of the Investigator (in all countries except Austria). In Austria, pregnant subjects are excluded from participation in the study.
- Are women of childbearing potential and are not using appropriate contraception (per the local DMF product information) as determined by the Investigator.
- Women who are breastfeeding may be excluded (per the local DMF product information) at the discretion of the Investigator.
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: Tecfidera, DMF, BG00012Administered as per the approved dosage in all countries where DMF has received marketing authorization. | Drug | DMF |
Primary outcome
Annualized Relapse Rate (ARR)
Time frame: 12 Months
16 secondary outcomes
Change from Baseline in Multiple Sclerosis Impact Scale (MSIS-29) score
Time frame: 12 Months
Change from Baseline in Modified Fatigue Impact Scale-5 Item (MFIS-5) score
Time frame: 12 Months
Change from Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) score
Time frame: 12 Months
Change from Baseline in EQ-5D 5 level version (EQ-5D-5L) index
Time frame: 12 Months
Change from Baseline in participants-Reported Indices for Multiple Sclerosis-Activity Limitations (PRIMUS-Activity Limitations) score
Time frame: 12 Months
Change from Baseline in Work Productivity and Activity Impairment-Multiple Sclerosis version (WPAI-MS) score
Time frame: 12 Months
Change from Baseline in Beck Depression Inventory-Fast Screen (BDI-Fast Screen) score
Time frame: 12 Months
Proportion of participants with confirmed (24-week) Expanded Disability Status Scale (EDSS) progression
Time frame: 12 Months
Annualized Relapse Rate (ARR) at Baseline (i.e., over the 12 months prior to enrollment) and at Month 6
Time frame: Baseline, 6 Months
The proportion of participants relapsed
Time frame: 12 Months
Number of participants who are hospitalized/have emergency room visits due to MS relapses or have relapses requiring intravenous (IV) steroid treatment during the study, or who make visits to neurologists/other specialists due to MS
Time frame: 12 Months
Proportion of participants who are hospitalized/have emergency room visits due to MS relapses or have relapses requiring intravenous (IV) steroid treatment during the study, or who make visits to neurologists/other specialists due to MS
Time frame: 12 Months
Proportion of participants who report taking the prescribed DMF dose
Time frame: 12 Months
Percentage of participants who report taking the prescribed DMF dose
Time frame: 12 Months
Reasons reported by participants for not taking prescribed DMF dose
Time frame: 12 Months
Change from baseline in EQ Visual Analog Scale (EQVAS) score
Time frame: 12 Months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2020.
- Derived from this study: PubMed 31832225Berger T, Brochet B, Brambilla L, Giacomini PS, Montalban X, Vasco Salgado A, Su R, Bretagne A. Effectiveness of delayed-release dimethyl fumarate on patient-reported outcomes and clinical measures in patients with relapsing-remitting multiple sclerosis in a real-world clinical setting: PROTEC. Mult Scler J Exp Transl Clin. 2019 Dec 2;5(4):2055217319887191. doi: 10.1177/2055217319887191. eCollection 2019 Oct-Dec.
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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
90 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing dimethyl fumarate in people with Relapsing-Remitting Multiple Sclerosis and Multiple Sclerosis, run by Biogen at 90 sites in 11 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 3 inclusion and 9 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 19 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 90 sites in France, Italy, Spain, Portugal, Austria and 6 more countries. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Annualized Relapse Rate (ARR) (time frame: 12 Months). 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 NCT01930708, which also lists 1 linked publication.
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 19 Mar 2020.