BG00012 Phase 2 Combination Study in Participants With Multiple Sclerosis

Multiple Sclerosis Clinical Trial

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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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01156311
• Other study ID #: 109MS201
• Status: Completed
• Phase: Phase 2
• First received: July 1, 2010
• Last updated: July 21, 2015
• Start date: June 2010
• Est. completion date: March 2012

Study information

• Verified date: July 2015
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: March 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 IFNß (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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing-Remitting Multiple Sclerosis
• Sclerosis

Intervention

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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Summary of Adverse Events (AEs) Occurring Before BG00012 Dosing (Monotherapy Period)	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.	from time of enrollment until day before first administration of BG00012 (Week -8 to Week 0)	Yes
Other	Average Number of Gadolinium (Gd)-Enhancing Lesions: Week -8, -4, 0 Average Versus Week 16, 20, 24 Average	The average is calculated as (total number of lesions in non-missing scans / number of non-missing magnetic resonance imaging [MRI] scans).	Week -8 through Week 24	No
Other	Average Number of New Gd-Enhancing Lesions: Weeks -4, 0 Average Versus Weeks 20, 24 Average	The average is calculated as (total number of lesions in non-missing scans / number of non-missing MRI scans).	Week -4 through Week 24	No
Other	Number of New or Newly Enlarging T2 Lesions	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.	Week -8 to Week 24	No
Primary	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).	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes