BG00012 Phase 2 Combination Study in Participants With Multiple Sclerosis

NCT01156311 | Completed Phase 2 Results

• 1 other identifier: 109MS201
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 16

Brief Summary

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).

Conditions

Relapsing-Remitting Multiple Sclerosis; Multiple Sclerosis

Keywords

BG00012; MS; RRMS

Outcome Measures

Primary Outcomes (4)

• Summary of Treatment-emergent Adverse Events (TEAEs) Occurring Post-BG00012 Dosing (Add-on Therapy Period)

  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.

  AEs were collected from enrollment until the final study visit (Week 26 +/-5 days).

• Potentially Clinically Significant Hematology Laboratory Abnormalities for Combination Therapy

  Percentage of participants with potentially clinically significant hematology laboratory abnormalities.

  collected from the start of BG00012 administration through to Week 26 +/- 5 days

• Maximum Post-Baseline Values: Liver Enzymes for Combination Therapy

  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.

  collected from the start of BG00012 administration through to Week 26 +/- 5 days

• Worst Post-Baseline Values for Selected Urinalysis Parameters That Require Further Evaluation for Combination Therapy

  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.

  collected from the start of BG00012 administration through to Week 26 +/- 5 days

Other Outcomes (4)

• Summary of Adverse Events (AEs) Occurring Before BG00012 Dosing (Monotherapy Period)

  from time of enrollment until day before first administration of BG00012 (Week -8 to Week 0)

• Average Number of Gadolinium (Gd)-Enhancing Lesions: Week -8, -4, 0 Average Versus Week 16, 20, 24 Average

  Week -8 through Week 24

• Average Number of New Gd-Enhancing Lesions: Weeks -4, 0 Average Versus Weeks 20, 24 Average

  Week -4 through Week 24

Study Arms (2)

Glatiramer acetate (GA) and dimethyl fumarate

EXPERIMENTAL

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

Interferon beta (IFNβ) and dimethyl fumarate

EXPERIMENTAL

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

Interventions

dimethyl fumarate DRUG

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.

Also known as: Tecfidera, DMF, BG00012

Glatiramer acetate (GA) and dimethyl fumarate; Interferon beta (IFNβ) and dimethyl fumarate

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biogen: lead

Study Sites (16)

Research Site

Gilbert, Arizona, United States

Location

Research Site

Phoenix, Arizona, United States

Location

Research Site

Danbury, Connecticut, United States

Location

Research Site

Atlanta, Georgia, United States

Location

Research Site

Fort Wayne, Indiana, United States

Location

Research Site

Baltimore, Maryland, United States

Location

Research Site

Boston, Massachusetts, United States

Location

Research Site

Golden Valley, Minnesota, United States

Location

Research Site

Teaneck, New Jersey, United States

Location

Research Site

Patchogue, New York, United States

Location

Research Site

Cleveland, Ohio, United States

Location

Research Site

Dayton, Ohio, United States

Location

Research Site

Portland, Oregon, United States

Location

Research Site

Cordova, Tennessee, United States

Location

Research Site

Franklin, Tennessee, United States

Location

Research Site

Milwaukee, Wisconsin, United States

Location

Related Publications (1)

• Calkwood J, Vollmer T, Fox RJ, Zhang R, Novas M, Sheikh SI, Viglietta V. Safety and Tolerability of Delayed-Release Dimethyl Fumarate Administered with Interferon Beta or Glatiramer Acetate in Relapsing-Remitting Multiple Sclerosis. Int J MS Care. 2016 May-Jun;18(3):138-46. doi: 10.7224/1537-2073.2015-020.

  PMID: 27252601 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Interventions

Dimethyl Fumarate

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Results Point of Contact

• Title: Biogen Study Medical Director
• Organization: Biogen

clinicaltrials@biogen.com

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2010
• First Posted: July 2, 2010
• Study Start: June 1, 2010
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: March 21, 2017
• Results First Posted: June 9, 2015

Record last verified: 2017-02

Locations

US (16)