BG00012 Phase 2 Combination Study in Participants With Multiple Sclerosis - Full Text View

Purpose

The primary objective of the study is to evaluate the safety and tolerability of BG00012 (dimethyl fumarate) administered in combination with interferon b (IFNß) or glatiramer acetate (GA) in participants with relapsing-remitting multiple sclerosis (RRMS).

Condition	Intervention	Phase
Relapsing-Remitting Multiple Sclerosis Multiple Sclerosis	Drug: dimethyl fumarate	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Open-Label, Multicenter Study in Subjects With Relapsing-Remitting Multiple Sclerosis to Evaluate the Safety of 240 mg BG00012 TID Administered as Add-On Therapy to Beta Interferons (IFNβ) or Glatiramer Acetate (GA)

Resource links provided by NLM:

Genetics Home Reference related topics: multiple sclerosis

MedlinePlus related topics: Multiple Sclerosis

Drug Information available for: Formic acid Dimethyl fumarate Interferon Glatiramer Glatiramer acetate

U.S. FDA Resources

Further study details as provided by Biogen:

Primary Outcome Measures:

Summary of Treatment-emergent Adverse Events (TEAEs) Occurring Post-BG00012 Dosing (Add-on Therapy Period) [ Time Frame: AEs were collected from enrollment until the final study visit (Week 26 +/-5 days). ] [ Designated as safety issue: Yes ]
An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not related to the study drug. A serious adverse event (SAE) was any untoward medical occurrence that, at any dose: resulted in death; in the view of the Investigator, placed the participant at immediate risk of death (a life-threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; was any other medically important event that, in the opinion of the Investigator, jeopardized the participant or required intervention to prevent one of the other outcomes above. TEAE was defined as having an onset date that was on or after the start of study treatment (BG00012), or that worsened after the start of study treatment.
Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy [ Time Frame: collected from the start of BG00012 administration through to Week 26 +/- 5 days ] [ Designated as safety issue: Yes ]
Percentage of participants with potentially clinically significant hematology laboratory abnormalities.
Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy [ Time Frame: collected from the start of BG00012 administration through to Week 26 +/- 5 days ] [ Designated as safety issue: Yes ]
Percentage of participants with post-baseline liver enzyme values above the upper limit of normal (ULN). Liver enzymes included alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and bilirubin. Elevated ALT/AST (ALT/AST ≥ 3*ULN) concurrent with elevated total bilirubin was also evaluated.
Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy [ Time Frame: collected from the start of BG00012 administration through to Week 26 +/- 5 days ] [ Designated as safety issue: Yes ]
Percentage of participants with post-baseline values for selected urinalysis parameters requiring further evaluation. For urine microscopy, results were categorized for male and female participants. For males, normal/negative was considered 0 to 3 red blood cells/high-power field (rbc/hpf), and positive was categorized in the following stages: 4 to 10, 11 to 20, 21 to 149, and ≥ 150 rbc/hpf. For females, normal/negative was considered 0 to 8 rbc/hpf, and positive was categorized in the following stages: 9 to 20, 21 to 30, 31 to 149, and ≥ 150 rbc/hpf.

Other Outcome Measures:

Summary of Adverse Events (AEs) Occurring Before BG00012 Dosing (Monotherapy Period) [ Time Frame: from time of enrollment until day before first administration of BG00012 (Week -8 to Week 0) ] [ Designated as safety issue: Yes ]
Percentage of participants with AEs, serious AEs (SAEs), and discontinuations due to AEs. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not related to the study drug. An SAE was any untoward medical occurrence that, at any dose: resulted in death; in the view of the Investigator, placed the participant at immediate risk of death (a life-threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; was any other medically important event that, in the opinion of the Investigator, jeopardized the participant or required intervention to prevent one of the other outcomes above. AEs were categorized as mild, moderate, or severe. All AEs occurring from enrollment to the day before BG00012 dosing are included.
Average Number of Gadolinium (Gd)-Enhancing Lesions: Week -8, -4, 0 Average Versus Week 16, 20, 24 Average [ Time Frame: Week -8 through Week 24 ] [ Designated as safety issue: No ]
The average is calculated as (total number of lesions in non-missing scans / number of non-missing magnetic resonance imaging [MRI] scans).
Average Number of New Gd-Enhancing Lesions: Weeks -4, 0 Average Versus Weeks 20, 24 Average [ Time Frame: Week -4 through Week 24 ] [ Designated as safety issue: No ]
The average is calculated as (total number of lesions in non-missing scans / number of non-missing MRI scans).
Number of New or Newly Enlarging T2 Lesions [ Time Frame: Week -8 to Week 24 ] [ Designated as safety issue: No ]
The number of new T2 lesions divided by the number of months since the reference visit during the Monotherapy Period and the Add-On Therapy Period.


Enrollment:	108
Study Start Date:	June 2010
Study Completion Date:	March 2012
Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Glatiramer acetate (GA) and dimethyl fumarate Participants taking a stable dose of GA for at least 12 months prior to the study remain on that dose throughout the study. Dimethyl fumarate is administered at 120 mg three times a day (TID) on Days 1-7, and 240 mg TID on Day 8 until the end of treatment (approximately 6 months).	Drug: dimethyl fumarate Days 1-7: 120 mg three times a day (TID) for a total daily dose of 360 mg. Day 8 to Week 24: 240 mg TID for a total daily dose of 720 mg. Drug supplied as a capsule taken orally. Other Names: Tecfidera DMF BG00012
Experimental: Interferon beta (IFNβ) and dimethyl fumarate Participants taking a stable dose of one of the IFNβ products for at least 12 months prior to the study remain on that product and dose throughout the study. Dimethyl fumarate is administered at 120 mg three times a day (TID) on Days 1-7, and 240 mg TID on Day 8 until the end of treatment (approximately 6 months).	Drug: dimethyl fumarate Days 1-7: 120 mg three times a day (TID) for a total daily dose of 360 mg. Day 8 to Week 24: 240 mg TID for a total daily dose of 720 mg. Drug supplied as a capsule taken orally. Other Names: Tecfidera DMF BG00012

Eligibility


Ages Eligible for Study:	18 Years to 55 Years (Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Key Inclusion Criteria:

Must have a confirmed diagnosis of relapsing-remitting multiple sclerosis (RRMS) according to McDonald criteria #1-4 (Polman et al, 2005 [Appendix I]), and have a prior brain magnetic resonance imaging (MRI) demonstrating lesion (s) consistent with multiple sclerosis (MS) from any point in time.
Must have an Expanded Disability Status Scale (EDSS) between 0.0 and 5.0, inclusive.
Must be taking the same dose of a prescribed IFNβ (either Avonex, Betaseron, Rebif) or GA for at least 12 months consecutively at the time of enrollment and remain on this treatment for the duration of the study. Participants receiving Rebif must be prescribed 44 μg by subcutaneous injection three times per week.

Key Exclusion Criteria:

Primary progressive, secondary progressive, or progressive relapsing MS (as defined by Polman et al. 2005).
Other chronic disease of the immune system, malignancies, acute urologic, or pulmonary disease.
Pregnant or nursing women.
Participation within 6 months prior to study enrollment in any other drug, biologic, or device study.

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: NCT01156311

Locations


United States, Arizona
Research Site
Gilbert, Arizona, United States
Research Site
Phoenix, Arizona, United States
United States, Connecticut
Research Site
Danbury, Connecticut, United States
United States, Georgia
Research Site
Atlanta, Georgia, United States
United States, Indiana
Research Site
Fort Wayne, Indiana, United States
United States, Maryland
Research Site
Baltimore, Maryland, United States
United States, Massachusetts
Research Site
Boston, Massachusetts, United States
United States, Minnesota
Research Site
Golden Valley, Minnesota, United States
United States, New Jersey
Research Site
Teaneck, New Jersey, United States
United States, New York
Research Site
Patchogue, New York, United States
United States, Ohio
Research Site
Cleveland, Ohio, United States
Research Site
Dayton, Ohio, United States
United States, Oregon
Research Site
Portland, Oregon, United States
United States, Tennessee
Research Site
Cordova, Tennessee, United States
Research Site
Franklin, Tennessee, United States
United States, Wisconsin
Research Site
Milwaukee, Wisconsin, United States

Sponsors and Collaborators

Biogen

Investigators


Study Director:	Medical Director	Biogen

More Information


Responsible Party:	Biogen
ClinicalTrials.gov Identifier:	NCT01156311 History of Changes
Other Study ID Numbers:	109MS201
Study First Received:	July 1, 2010
Results First Received:	May 26, 2015
Last Updated:	July 21, 2015
Health Authority:	United States: Food and Drug Administration

Keywords provided by Biogen:


BG00012 MS RRMS

Additional relevant MeSH terms:


Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting Sclerosis Pathologic Processes Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Nervous System Diseases Demyelinating Diseases Autoimmune Diseases Immune System Diseases Interferons	Glatiramer Acetate Dimethyl Fumarate Antineoplastic Agents Antiviral Agents Anti-Infective Agents Adjuvants, Immunologic Immunologic Factors Physiological Effects of Drugs Immunosuppressive Agents Antirheumatic Agents Dermatologic Agents

ClinicalTrials.gov processed this record on September 23, 2016

BG00012 Phase 2 Combination Study in Participants With Multiple Sclerosis (EXPLORE)