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

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ClinicalTrials.gov Identifier: NCT01156311
Recruitment Status : Completed
First Posted : July 2, 2010
Results First Posted : June 9, 2015
Last Update Posted : March 21, 2017
Sponsor:
Information provided by (Responsible Party):
Biogen

Tracking Information
First Submitted Date  ICMJE July 1, 2010
First Posted Date  ICMJE July 2, 2010
Results First Submitted Date  ICMJE May 26, 2015
Results First Posted Date  ICMJE June 9, 2015
Last Update Posted Date March 21, 2017
Study Start Date  ICMJE June 2010
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 12, 2015)
  • 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). ]
    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 ]
    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 ]
    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 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 1, 2010)
The primary objective of the study is to evaluate the safety and tolerability of BG00012 administered in combination with IFNβ or GA in subjects with RRMS. [ Time Frame: 9 Months ]
Change History Complete list of historical versions of study NCT01156311 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: July 1, 2010)
  • Explore the efficacy of BG00012 in combination with IFNβ or GA. [ Time Frame: 9 Months ]
  • Explore the effect of combination therapy on potential biomarkers of BG00012 and neopterin for IFNβ and IFNβ with BG00012. [ Time Frame: 9 Months ]
Current Other Pre-specified Outcome Measures
 (submitted: June 12, 2015)
  • 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) ]
    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 ]
    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 ]
    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 ]
    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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE BG00012 Phase 2 Combination Study in Participants With Multiple Sclerosis
Official Title  ICMJE 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)
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Relapsing-Remitting Multiple Sclerosis
  • Multiple Sclerosis
Intervention  ICMJE 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
Study Arms  ICMJE
  • 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).
    Intervention: Drug: dimethyl fumarate
  • 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).
    Intervention: Drug: dimethyl fumarate
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 2, 2014)
108
Original Estimated Enrollment  ICMJE
 (submitted: July 1, 2010)
100
Actual Study Completion Date  ICMJE March 2012
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01156311
Other Study ID Numbers  ICMJE 109MS201
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Biogen
Study Sponsor  ICMJE Biogen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Biogen
PRS Account Biogen
Verification Date February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP