BG00012 Monotherapy Safety and Efficacy Extension Study in Multiple Sclerosis (MS) (ENDORSE)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Biogen
ClinicalTrials.gov Identifier:
NCT00835770
First received: February 2, 2009
Last updated: October 16, 2015
Last verified: October 2015
  Purpose
The primary objective of this study is to evaluate the long-term safety profile of BG00012 (dimethyl fumarate). Secondary objectives of this study are to evaluate the long-term efficacy of BG00012 using clinical endpoints and disability progression, to evaluate further the long-term effects of BG00012 on multiple sclerosis (MS) brain lesions on magnetic resonance imaging (MRI) scans in participants who had MRI scans as part of Studies 109MS301 (NCT00420212) and 109MS302 (NCT00451451) and to evaluate the long-term effects of BG00012 on health economics assessments and the visual function test.

Condition Intervention Phase
Relapsing-Remitting Multiple Sclerosis
Drug: dimethyl fumarate
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Dose-Blind, Multicenter, Extension Study to Determine the Long-Term Safety and Efficacy of Two Doses of BG00012 Monotherapy in Subjects With Relapsing-Remitting Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by Biogen:

Primary Outcome Measures:
  • Number of Participants with Adverse Events [ Time Frame: Day 1 up to 8 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of Participants Who Had Relapses [ Time Frame: Day 1 up to 8 years ] [ Designated as safety issue: No ]
  • Annualized Relapse Rate (ARR) [ Time Frame: Day 1 up to 8 years ] [ Designated as safety issue: No ]
  • Change from Baseline in the Expanded Disability Status Scale (EDSS) up to 8 years [ Time Frame: Day 1 up to 8 years ] [ Designated as safety issue: No ]
    Progression of disability is defined as at least a 1.0 point increase on the EDSS from baseline EDSS 1.0 that is sustained for 24 weeks or at least a 1.5 point increase on the EDSS from baseline EDSS =0 that is sustained for 24 weeks. 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.

  • Number and volume of Gd-enhancing lesions as Measured by Magnetic Resonance Imaging (MRI) [ Time Frame: Day 1 up to 8 years ] [ Designated as safety issue: No ]
  • Number and volume of new or newly-enlarging T2 lesions as Measured by Magnetic Resonance Imaging (MRI) [ Time Frame: Day 1 up to 8 years ] [ Designated as safety issue: No ]
  • Number and volume of T1 hypointense lesions [ Time Frame: Day 1 up to 8 years ] [ Designated as safety issue: No ]
  • Change from Baseline in Brain atrophy up to 8 years [ Time Frame: Day 1 up to 8 years ] [ Designated as safety issue: No ]
  • Summary of Magnetization Transfer Ratio (MTR) [ Time Frame: Day 1 up to 8 years ] [ Designated as safety issue: No ]
    MTR is used in neuroradiology to highlight abnormalities in brain structures

  • Change from Baseline in EQ-5D Health Survey (EQ-5D) up to 8 years [ Time Frame: Day 1 up to 8 years ] [ Designated as safety issue: No ]
    EQ-5D is a self-administered questionnaire consisting of 5 sets of 3 questions pertaining to specific health states (i.e., mobility, self-care, pain, usual activities, anxiety), a health status rating scale, and demographic questions.

  • Change from baseline in SF-36® Health Survey (SF-36) up to 8 years [ Time Frame: Day 1 up to 8 years ] [ Designated as safety issue: No ]
    The 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.

  • Change from Baseline in Visual Function test scores up to 8 years [ Time Frame: Day 1 up to 8 years ] [ Designated as safety issue: No ]

Enrollment: 1738
Study Start Date: February 2009
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BG00012 plus placebo
In the first phase, participants will receive BG00012 240 mg (two 120 mg capsules) twice a day (BID) and 2 placebo capsules once a day. In the second phase participants will receive open-label BG00012 240 mg BID, for up to 8 years.
Drug: dimethyl fumarate
BG00012 capsules
Other Names:
  • BG00012
  • Tecfidera
  • DMF
Drug: Placebo
Capsules taken to maintain the blind in the 240 mg BID treatment group.
Experimental: BG00012
In the first phase participants will receive BG00012 240 mg (two 120 mg capsules) three times a day (TID). In the second phase participants will receive open-label BG00012 240 mg BID for up to 8 years.
Drug: dimethyl fumarate
BG00012 capsules
Other Names:
  • BG00012
  • Tecfidera
  • DMF

Detailed Description:
The initial BG00012 dosage for the extension study (240 mg BID or 240 mg TID) was the same as that used in the Phase 3 Studies 109MS301 (NCT00420212) and 109MS302 (NCT00451451). Subsequent to the initiation of this study, BG00012 was approved in several countries for the treatment of MS at a dose of 240 mg BID. For this reason, all participants continuing in this study will receive the currently marketed dose of 240 mg BID.
  Eligibility

Ages Eligible for Study:   19 Years to 58 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

-Subjects who participated in and completed as per protocol previous BG00012 clinical studies 109MS301 (NCT00420212) or 109MS302 (NCT00451451).

Key Exclusion Criteria:

  • Any significant change in medical history from 109MS301 or 109MS302 that would have excluded subject's participation from their previous study.
  • Subjects from 109MS301 or 109MS302 who discontinued oral study treatment due to an AE or due to reasons other than protocol-defined relapse/disability progression.
  • Subjects from 109MS301 or 109MS302 who discontinued study treatment due to disability progression or relapses and did not follow the modified visit schedule up to Week 96.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00835770

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Sponsors and Collaborators
Biogen
Investigators
Study Director: Medical Director Biogen
  More Information

No publications provided

Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT00835770     History of Changes
Other Study ID Numbers: 109MS303  2008-004753-14 
Study First Received: February 2, 2009
Last Updated: October 16, 2015
Health Authority: Israel: Ministry of Health
Belgium: Federal Agency for Medicinal Products and Health Products
Bulgaria: Bulgarian Drug Agency
Romania: National Agency for Medicines and Medical Devices
Switzerland: Swissmedic
Ukraine: State Pharmacological Center - Ministry of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Macedonia: Ministry of Health
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Guatemala: Ministry of Public Health and Social Assistance
Australia: Department of Health and Ageing Therapeutic Goods Administration
New Zealand: Ministry of Health
Bosnia: Federal Ministry of Health
Serbia: Medicines and Medical Devices Agency of Serbia
Italy: The Italian Medicines Agency
Mexico: Federal Commission for Sanitary Risks Protection
Estonia: The State Agency of Medicine
Austria: Agency for Health and Food Safety
South Africa: Medicines Control Council
Czech Republic: State Institute for Drug Control
Greece: National Organization of Medicines
Slovakia: State Institute for Drug Control
Germany: Federal Institute for Drugs and Medical Devices
Croatia: Ministry of Health and Social Care
Belarus: Ministry of Health
Canada: Health Canada
Ireland: Health Products Regulatory Authority
France: Agence Nationale de Sécurité du Médicament et des produits de santé (ANSM)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
United States: Food and Drug Administration
India: Drugs Controller General of India
Latvia: State Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Moldova: Ministry of Health

Keywords provided by Biogen:
relapsing
multiple sclerosis
remitting
oral

Additional relevant MeSH terms:
Dimethyl fumarate
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes
Dermatologic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 11, 2016