Phase 4 Gastrointestinal Tolerability Study of Dimethyl Fumarate in Patients With Relapsing Forms of Multiple Sclerosis in the United States (MANAGE)

A Multicenter, Open-Label, Single-Arm Study of Gastrointestinal Tolerability in Patients With Relapsing Forms of Multiple Sclerosis Receiving Tecfidera™ (Dimethyl Fumarate) Delayed-release Capsules

The primary objective of this study is to evaluate the effect of symptomatic therapies on gastrointestinal (GI)-related events reported by participants with relapsing forms of multiple sclerosis (MS) initiating therapy with dimethyl fumarate (DMF) in the clinical practice setting.

The secondary objectives of this study are as follows:

• To evaluate GI-related events requiring symptomatic therapy and the role of those therapies over time in participants with relapsing forms of MS initiating therapy with DMF in the clinical practice setting.
• To evaluate GI-related events that lead to DMF discontinuation after the use of symptomatic therapy in participants with relapsing forms of MS initiating therapy with DMF in the clinical practice setting.

Study Overview

• Status: Completed
• Conditions: Relapsing Forms of Multiple Sclerosis
• Intervention / Treatment: Drug: BG00012 (DMF)

• Study Type: Interventional
• Enrollment (Actual): 237
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Cullman, Alabama, United States, 35058
      • Research Site
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Research Site
    • Scottsdale, Arizona, United States, 85258
      • Research Site
  • California
    • Fullerton, California, United States, 92835
      • Research Site
    • Newport Beach, California, United States, 92663
      • Research Site
    • Pasadena, California, United States, 91105
      • Research Site
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Research Site
    • Fort Collins, Colorado, United States, 80528
      • Research Site
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Research Site
  • Florida
    • Maitland, Florida, United States, 32751
      • Research Site
    • Naples, Florida, United States, 34102
      • Research Site
    • North Palm Beach, Florida, United States, 33408
      • Research Site
    • Port Charlotte, Florida, United States, 33952
      • Research Site
    • Sarasota, Florida, United States, 34239
      • Research Site
    • St. Petersburg, Florida, United States, 33713
      • Research Site
    • Tampa, Florida, United States, 33612
      • Research Site
    • Tampa, Florida, United States, 33609
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30327
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Research Site
  • Massachusetts
    • Milford, Massachusetts, United States, 01757
      • Research Site
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • Research Site
  • New York
    • Patchogue, New York, United States, 11772
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Research Site
    • Greensboro, North Carolina, United States, 27405
      • Research Site
    • High Point, North Carolina, United States, 27262
      • Research Site
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97225
      • Research Site
  • Pennsylvania
    • Monroeville, Pennsylvania, United States, 15215
      • Research Site
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Research Site
    • Franklin, Tennessee, United States, 37064
      • Research Site
    • Knoxville, Tennessee, United States, 37934
      • Research Site
  • Texas
    • Round Rock, Texas, United States, 78681
      • Research Site
  • Utah
    • Salt Lake City, Utah, United States, 84103
      • Research Site
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Research Site
    • Roanoke, Virginia, United States, 24018
      • Research Site
  • Washington
    • Tacoma, Washington, United States, 98405
      • Research Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Decision to treat with DMF must precede enrollment.
• Naïve to DMF or fumaric acid esters.
• Resides in the US and has a confirmed diagnosis of a relapsing form of MS.
• Satisfies the approved therapeutic indication(s) for DMF.

Key Exclusion Criteria:

• Inability to comply with study requirements or, at the discretion of the Investigator, is deemed unsuitable for study participation.
• History of significant GI disease, chronic use of GI symptomatic therapy, active malignancies.
• Is participating in any other interventional clinical trial.

NOTE: Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dimethyl Fumarate; 120 mg DMF twice daily (BID) for the first 7 days and 240 mg DMF BID thereafter for 12 weeks of treatment. Participants will be instructed to take the DMF dose with food (with a meal or within 1 hour after a meal).	Drug: BG00012 (DMF); Other Names: DMF; Tecfidera; dimethyl fumarate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Worst Severity Score of Overall Gastrointestinal (GI) Events, Modified Overall GI Symptom Scale (MOGISS)	Severity of GI-related events in DMF-treated participants using the MOGISS to measure GI symptoms, based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms.	12 Weeks
Worst Severity Score of Overall GI Events, Modified Acute Gl Symptom Scale	Severity of GI-related events in DMF-treated participants using the MAGISS to measure GI symptoms, based on a 0- to 10-point scale, with 0 representing absence of symptoms and 10 representing the most severe symptoms.	12 Weeks
Percentage of DMF-treated Participants Who Reported GI-related Symptoms and Who Utilized Symptomatic Therapy	Percentage of participants reporting GI symptoms on the MOGISS, by those who utilized symptomatic therapy.	12 Weeks
Duration of GI-related Episodes in DMF-treated Participants	In participants who took symptomatic therapy, the median duration of acute GI episodes (in hours) was summarized for the overall treatment period, by symptom (nausea, diarrhea, lower abdominal pain, upper abdominal pain, vomiting, indigestion, constipation, bloating, and flatulence). Table only includes the symptom duration for those symptoms with start and stop times entered in the eDiary (evaluable GI episodes), based on the MAGISS.	12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of DMF-treated Participants Who Required GI Symptomatic Therapy	Percentage of participants reporting that they required GI symptomatic therapy, based on the MOGISS.	12 Weeks
Participants' Use of Symptomatic Therapy, by Type and Category	The symptomatic therapies used by DMF-treated participants were self-reported by type and category. Each participant may have taken more than one symptomatic therapy type but was counted only once within each therapy category. Acetylsalicylic acid (ASA) is abbreviated in the table.	12 Weeks
Summary of Use and Days on Symptomatic Therapy, by Category	The total duration (in days) of use of each symptomatic therapy by participants as a result of GI symptoms experienced by DMF-treated participants is presented. If a participant had multiple different therapies on the same day, the days on symptomatic therapy was calculated as 1 day in the 'All Therapies' category.	12 Weeks
Number of DMF-treated Participants Who Discontinued DMF Due to GI-related Events Requiring Symptomatic Therapy	The last symptomatic therapy prior to last dose of study medication was used to summarize the number of participants who discontinued DMF due to GI-related events. Participants may have taken more than one symptomatic therapy but are counted only once in the 'All Therapies' category.	12 Weeks

Collaborators and Investigators

• Sponsor: Biogen

Publications and helpful links

General Publications

• Fox EJ, Vasquez A, Grainger W, Ma TS, von Hehn C, Walsh J, Li J, Zambrano J. Gastrointestinal Tolerability of Delayed-Release Dimethyl Fumarate in a Multicenter, Open-Label Study of Patients with Relapsing Forms of Multiple Sclerosis (MANAGE). Int J MS Care. 2016 Jan-Feb;18(1):9-18. doi: 10.7224/1537-2073.2014-101.

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: May 9, 2013
• First Submitted That Met QC Criteria: June 6, 2013
• First Posted (Estimate): June 10, 2013

Study Record Updates

• Last Update Posted (Actual): March 21, 2017
• Last Update Submitted That Met QC Criteria: February 14, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Dimethyl Fumarate
• Other Study ID Numbers: 109MS403