A Study Evaluating the Effectiveness of Tecfidera (Dimethyl Fumarate) on Multiple Sclerosis (MS) Disease Activity and Patient-Reported Outcomes (PROTEC)

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Relapsing-Remitting Multiple Sclerosis
• Intervention / Treatment: Drug: dimethyl fumarate

• Study Type: Interventional
• Enrollment (Actual): 1114
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Research Site
  • Klagenfurt, Austria, 9026
    • Research Site
  • Linz, Austria, 4020
    • Research Site
  • Salzburg, Austria, 5020
    • Research Site
  • St. Polten, Austria, 3100
    • Research Site
  • Villach, Austria, 9500
    • Research Site
  • Wien, Austria, 1090
    • Research Site
  • Wien, Austria, 1220
    • Research Site
• Belgium
  • Brugge, Belgium, 8000
    • Research Site
  • Bruxelles, Belgium, 1200
    • Research Site
  • Melsbroek, Belgium, 1820
    • Research Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Research Site
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 1J6
      • Research Site
  • New Brunswick
    • St. John's, New Brunswick, Canada, E2K 5S9
      • Research Site
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Research Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • Research Site
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • Research Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H8A 2B4
      • Research Site
• Czechia
  • Brno, Czechia, 625 00
    • Research Site
  • Havirov, Czechia, 736 00
    • Research Site
  • Hradec Kralove, Czechia, 500 05
    • Research Site
  • Olomouc, Czechia, 775 20
    • Research Site
  • Pardubice, Czechia, 532 03
    • Research Site
  • Praha 10, Czechia, 100 34
    • Research Site
  • Praha 2, Czechia, 128 08
    • Research Site
• France
  • Nancy, France, 54035
    • Research Site
  • Rouen Cedex, France, 76031
    • Research Site
  • Bas Rhin
    • Strasbourg Cedex, Bas Rhin, France, 67098
      • Research Site
  • Cote dÝOr
    • Dijon Cedex, Cote dÝOr, France, 21079
      • Research Site
  • Doubs
    • Besancon cedex, Doubs, France, 25030
      • Research Site
  • Gard
    • Nimes, Gard, France, 30029
      • Research Site
  • Gironde
    • Bordeaux Cedex, Gironde, France, 33076
      • Research Site
  • Haut Rhin
    • Colmar cedex, Haut Rhin, France, 68024
      • Research Site
  • Haute Garonne
    • Toulouse cedex 1, Haute Garonne, France, 31059
      • Research Site
  • Haute Vienne
    • Limoges cedex, Haute Vienne, France, 87042
      • Research Site
  • Ille Et Vilaine
    • Rennes cedex 09, Ille Et Vilaine, France, 35033
      • Research Site
  • Isere
    • Grenoble cedex 09, Isere, France, 39043
      • Research Site
  • Loire Atlantique
    • Nantes cedex 1, Loire Atlantique, France, 44093
      • Research Site
  • Marne
    • Reims, Marne, France, 51092
      • Research Site
  • Nord
    • Lille Cedex, Nord, France, 59020
      • Research Site
    • Lille Cedex, Nord, France, 59037
      • Research Site
  • Vendee
    • La Roche sur Yon, Vendee, France, 85025
      • Research Site
  • Vienne
    • Poitiers cedex, Vienne, France, 86021
      • Research Site
  • Yvelines
    • Le Chesnay Cedex, Yvelines, France, 78157
      • Research Site
• Hungary
  • Budapest, Hungary, 1083
    • Research Site
  • Budapest, Hungary, 1076
    • Research Site
  • Debrecen, Hungary, 4032
    • Research Site
  • Pecs, Hungary, 7623
    • Research Site
  • Szeged, Hungary, 6725
    • Research Site
  • Veszprem, Hungary, 8200
    • Research Site
• Italy
  • Ancona, Italy, 60126
    • Research Site
  • Bergamo, Italy, 24100
    • Research Site
  • Bolzano, Italy, 39100
    • Research Site
  • Castelfiorentino, Italy, 50051
    • Research Site
  • Firenze, Italy, 50139
    • Research Site
  • Genova, Italy, 16153
    • Research Site
  • Messina, Italy, 98121
    • Research Site
  • Milano, Italy, 20133
    • Research Site
  • Napoli, Italy, 80131
    • Research Site
  • Perugia, Italy, 06156
    • Research Site
  • Pozzilli, Italy, 86077
    • Research Site
  • Roma, Italy, 00135
    • Research Site
  • Roma, Italy, 00189
    • Research Site
  • Siena, Italy, 53100
    • Research Site
  • Torino, Italy, 10124
    • Research Site
• Portugal
  • Almada, Portugal, 2801-915
    • Research Site
  • Amadora, Portugal, 2720-276
    • Research Site
  • Guimarães, Portugal, 4835-044
    • Research Site
  • Lisboa, Portugal, 1169-050
    • Research Site
  • Lisboa, Portugal, 1649-035
    • Research Site
  • Loures, Portugal, 2674-514
    • Research Site
  • Porto, Portugal, 4099-001
    • Research Site
  • Porto, Portugal, 4200-319
    • Research Site
  • Setúbal, Portugal, 2910-446
    • Research Site
• Slovakia
  • Bratislava, Slovakia, 81369
    • Research Site
  • Presov, Slovakia, 8081
    • Research Site
• Slovenia
  • Ljubljana, Slovenia, SI-1525
    • Research Site
  • Maribor, Slovenia, 2000
    • Research Site
• Spain
  • Barcelona, Spain, 8035
    • Research Site
  • Bilbao, Spain, 48013
    • Research Site
  • Córdoba, Spain, 14011
    • Research Site
  • El Palmar, Spain, 30120
    • Research Site
  • Girona, Spain, 17007
    • Research Site
  • Malaga, Spain, 29010
    • Research Site
  • Sevilla, Spain, 41009
    • Research Site
  • Valencia, Spain, 46026
    • Research Site
  • Vigo, Spain, 36204
    • Research Site
  • Zaragoza, Spain, 50009
    • Research Site
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• 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:

• 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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DMF; 120 mg capsule oral twice daily (BID) during the first week and 240 mg BID thereafter.	Drug: dimethyl fumarate; Administered as per the approved dosage in all countries where DMF has received marketing authorization.; Other Names: BG00012; DMF; Tecfidera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Annualized Relapse Rate (ARR)	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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).	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.	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.	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.	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.	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.	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.	12 Months
Annualized Relapse Rate (ARR) at Baseline (i.e., over the 12 months prior to enrollment) and at Month 6		Baseline, 6 Months
The proportion of participants relapsed		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		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		12 Months
Proportion of participants who report taking the prescribed DMF dose		12 Months
Percentage of participants who report taking the prescribed DMF dose		12 Months
Reasons reported by participants for not taking prescribed DMF dose		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).	12 Months

Collaborators and Investigators

• Sponsor: Biogen

Publications and helpful links

General 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. Erratum In: Mult Scler J Exp Transl Clin. 2020 Apr 29;6(2):2055217320921146.

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2013
• Primary Completion (Actual): March 31, 2016
• Study Completion (Actual): January 9, 2020

Study Registration Dates

• First Submitted: August 15, 2013
• First Submitted That Met QC Criteria: August 26, 2013
• First Posted (Estimate): August 29, 2013

Study Record Updates

• Last Update Posted (Actual): March 19, 2020
• Last Update Submitted That Met QC Criteria: March 18, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: BG-12
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Dimethyl Fumarate
• Other Study ID Numbers: 109MS408; 2013-001656-35 (EudraCT Number)