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

Sponsor

Biogen (Industry)

Overall Status

Completed

CT.gov ID

NCT01930708

Collaborator

(none)

1,114

Enrollment

Locations

Arm

74.3

Actual Duration (Months)

12.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

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.

Condition or Disease	Intervention/Treatment	Phase
Relapsing-Remitting Multiple Sclerosis Multiple Sclerosis	Drug: dimethyl fumarate	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

1114 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 31, 2013

Actual Primary Completion Date :

Mar 31, 2016

Actual Study Completion Date :

Jan 9, 2020

Arms and Interventions

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: Tecfidera DMF BG00012

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:

Tecfidera

DMF

BG00012

Outcome Measures

Primary Outcome Measures

Annualized Relapse Rate (ARR) [12 Months]

Secondary Outcome Measures

Change from Baseline in Multiple Sclerosis Impact Scale (MSIS-29) score [12 Months]
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).
Change from Baseline in Modified Fatigue Impact Scale-5 Item (MFIS-5) score [12 Months]
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).
Change from Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) score [12 Months]
This is a validated, 14-item questionnaire that measures a participant's level of satisfaction/dissatisfaction with medication.
Change from Baseline in EQ-5D 5 level version (EQ-5D-5L) index [12 Months]
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.
Change from Baseline in participants-Reported Indices for Multiple Sclerosis-Activity Limitations (PRIMUS-Activity Limitations) score [12 Months]
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.
Change from Baseline in Work Productivity and Activity Impairment-Multiple Sclerosis version (WPAI-MS) score [12 Months]
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.
Change from Baseline in Beck Depression Inventory-Fast Screen (BDI-Fast Screen) score [12 Months]
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.
Proportion of participants with confirmed (24-week) Expanded Disability Status Scale (EDSS) progression [12 Months]
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.
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 [12 Months]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Innsbruck		Austria	6020
2	Research Site	Klagenfurt		Austria	9026
3	Research Site	Linz		Austria	4020
4	Research Site	Salzburg		Austria	5020
5	Research Site	St. Polten		Austria	3100
6	Research Site	Villach		Austria	9500
7	Research Site	Wien		Austria	1090
8	Research Site	Wien		Austria	1220
9	Research Site	Brugge		Belgium	8000
10	Research Site	Bruxelles		Belgium	1200
11	Research Site	Melsbroek		Belgium	1820
12	Research Site	Calgary	Alberta	Canada	T2N 2T9
13	Research Site	Victoria	British Columbia	Canada	V8R 1J6
14	Research Site	St. John's	New Brunswick	Canada	E2K 5S9
15	Research Site	St. John's	Newfoundland and Labrador	Canada	A1B 3V6
16	Research Site	Halifax	Nova Scotia	Canada	B3H 3A7
17	Research Site	London	Ontario	Canada	N6A 5A5
18	Research Site	Ottawa	Ontario	Canada	K1H 8L6
19	Research Site	Montreal	Quebec	Canada	H8A 2B4
20	Research Site	Brno		Czechia	625 00
21	Research Site	Havirov		Czechia	736 00
22	Research Site	Hradec Kralove		Czechia	500 05
23	Research Site	Olomouc		Czechia	775 20
24	Research Site	Pardubice		Czechia	532 03
25	Research Site	Praha 10		Czechia	100 34
26	Research Site	Praha 2		Czechia	128 08
27	Research Site	Strasbourg Cedex	Bas Rhin	France	67098
28	Research Site	Dijon Cedex	Cote dÝOr	France	21079
29	Research Site	Besancon cedex	Doubs	France	25030
30	Research Site	Nimes	Gard	France	30029
31	Research Site	Bordeaux Cedex	Gironde	France	33076
32	Research Site	Colmar cedex	Haut Rhin	France	68024
33	Research Site	Toulouse cedex 1	Haute Garonne	France	31059
34	Research Site	Limoges cedex	Haute Vienne	France	87042
35	Research Site	Rennes cedex 09	Ille Et Vilaine	France	35033
36	Research Site	Grenoble cedex 09	Isere	France	39043
37	Research Site	Nantes cedex 1	Loire Atlantique	France	44093
38	Research Site	Reims	Marne	France	51092
39	Research Site	Lille Cedex	Nord	France	59020
40	Research Site	Lille Cedex	Nord	France	59037
41	Research Site	La Roche sur Yon	Vendee	France	85025
42	Research Site	Poitiers cedex	Vienne	France	86021
43	Research Site	Le Chesnay Cedex	Yvelines	France	78157
44	Research Site	Nancy		France	54035
45	Research Site	Rouen Cedex		France	76031
46	Research Site	Budapest		Hungary	1076
47	Research Site	Budapest		Hungary	1083
48	Research Site	Debrecen		Hungary	4032
49	Research Site	Pecs		Hungary	7623
50	Research Site	Szeged		Hungary	6725
51	Research Site	Veszprem		Hungary	8200
52	Research Site	Ancona		Italy	60126
53	Research Site	Bergamo		Italy	24100
54	Research Site	Bolzano		Italy	39100
55	Research Site	Castelfiorentino		Italy	50051
56	Research Site	Firenze		Italy	50139
57	Research Site	Genova		Italy	16153
58	Research Site	Messina		Italy	98121
59	Research Site	Milano		Italy	20133
60	Research Site	Napoli		Italy	80131
61	Research Site	Perugia		Italy	06156
62	Research Site	Pozzilli		Italy	86077
63	Research Site	Roma		Italy	00135
64	Research Site	Roma		Italy	00189
65	Research Site	Siena		Italy	53100
66	Research Site	Torino		Italy	10124
67	Research Site	Almada		Portugal	2801-915
68	Research Site	Amadora		Portugal	2720-276
69	Research Site	Guimarães		Portugal	4835-044
70	Research Site	Lisboa		Portugal	1169-050
71	Research Site	Lisboa		Portugal	1649-035
72	Research Site	Loures		Portugal	2674-514
73	Research Site	Porto		Portugal	4099-001
74	Research Site	Porto		Portugal	4200-319
75	Research Site	Setúbal		Portugal	2910-446
76	Research Site	Bratislava		Slovakia	81369
77	Research Site	Presov		Slovakia	8081
78	Research Site	Ljubljana		Slovenia	SI-1525
79	Research Site	Maribor		Slovenia	2000
80	Research Site	Majadahonda	Madrid	Spain	28222
81	Research Site	Barcelona		Spain	8035
82	Research Site	Bilbao		Spain	48013
83	Research Site	Córdoba		Spain	14011
84	Research Site	El Palmar		Spain	30120
85	Research Site	Girona		Spain	17007
86	Research Site	Malaga		Spain	29010
87	Research Site	Sevilla		Spain	41009
88	Research Site	Valencia		Spain	46026
89	Research Site	Vigo		Spain	36204
90	Research Site	Zaragoza		Spain	50009