Relapsing Forms of Multiple SclerosisPhase 4MANAGENCT01873417

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

A Phase 4 study testing BG00012 (DMF) in people with Relapsing Forms of Multiple Sclerosis, run by Biogen at 37 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Relapsing Forms of Multiple Sclerosis
What is being tested?: BG00012 (DMF)
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 237 participants
Where: 37 sitesUnited States
Study dates: May 2013to Nov 2013
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

37 sites in 1 country.

City, postcode or hospital

37 sites in 1 country

United States37 sites

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

Other trials in United States

About this study

Official title: 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 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.

Conditions: Relapsing Forms of Multiple Sclerosis
Being tested: BG00012 (DMF)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BG00012 (DMF)Drug
Also called Tecfidera, DMF, dimethyl fumarate

Study groups in NCT01873417
Study group	Role	What they receive
Dimethyl Fumarate	Experimental	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). Receives: Drug: BG00012 (DMF)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 12 Weeks

Secondary outcomes (4)

Percentage of DMF-treated Participants Who Required GI Symptomatic Therapy
Percentage of participants reporting that they required GI symptomatic therapy, based on the MOGISS.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 12 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2013Nov 2013

First posted10 Jun 2013 (estimated)
Study startMay 2013
Primary completionNov 2013
Study completionNov 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Relapsing Forms of Multiple SclerosisStudies of the same condition, open and under way.
More trials run by BiogenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 237 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01873417
Sponsor's protocol ID: 109MS403
Acronym: MANAGE
Status last verified: Feb 2017
First submitted: 9 May 2013
Last updated: 21 Mar 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

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.
PubMed 26917993

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Relapsing Forms of Multiple Sclerosis trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT01873417
Acronym / sponsor ID: MANAGE / 109MS403
Conditions: Relapsing Forms of Multiple Sclerosis
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 237 participants (actual)
Lead sponsor: BiogenIndustry (pharma, biotech, devices)
Study start: May 2013
Primary completion: Nov 2013 (actual)
Study completion: Nov 2013 (actual)
First posted: 10 Jun 2013 (estimated)
Results: Posted 11 Nov 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Dimethyl Fumarate	Experimental	Drug: BG00012 (DMF)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).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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 (4 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BG00012 (DMF)Also: Tecfidera, DMF, dimethyl fumarate	Drug	Dimethyl Fumarate

Primary outcome

Worst Severity Score of Overall Gastrointestinal (GI) Events, Modified Overall GI Symptom Scale (MOGISS)
Time frame: 12 Weeks
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.
Worst Severity Score of Overall GI Events, Modified Acute Gl Symptom Scale
Time frame: 12 Weeks
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.
Percentage of DMF-treated Participants Who Reported GI-related Symptoms and Who Utilized Symptomatic Therapy
Time frame: 12 Weeks
Percentage of participants reporting GI symptoms on the MOGISS, by those who utilized symptomatic therapy.
Duration of GI-related Episodes in DMF-treated Participants
Time frame: 12 Weeks
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.

4 secondary outcomes

Percentage of DMF-treated Participants Who Required GI Symptomatic Therapy
Time frame: 12 Weeks
Participants' Use of Symptomatic Therapy, by Type and Category
Time frame: 12 Weeks
Summary of Use and Days on Symptomatic Therapy, by Category
Time frame: 12 Weeks
Number of DMF-treated Participants Who Discontinued DMF Due to GI-related Events Requiring Symptomatic Therapy
Time frame: 12 Weeks

Results and safety

Results posted to the registry on 11 Nov 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dimethyl Fumarate	237	202

Primary outcome: Worst Severity Score of Overall Gastrointestinal (GI) Events, Modified Overall GI Symptom Scale (MOGISS)

Time frame: 12 Weeks. Mean (Standard Deviation). Unit: units on a scale

Measure	Dimethyl Fumarate n = 128
Value	4.8 (2.34)

Population analysed: Evaluable participants (treated participants who utilized symptomatic therapy during the overall treatment period \[12 weeks\]).

Primary outcome: Worst Severity Score of Overall GI Events, Modified Acute Gl Symptom Scale

Time frame: 12 Weeks. Mean (Standard Deviation). Unit: units on a scale

Measure	Dimethyl Fumarate n = 128
Value	4.7 (2.13)

Population analysed: Evaluable participants (treated participants who utilized symptomatic therapy during the overall treatment period \[12 weeks\]).

Primary outcome: Percentage of DMF-treated Participants Who Reported GI-related Symptoms and Who Utilized Symptomatic Therapy

Time frame: 12 Weeks. Number. Unit: percentage of participants

Measure	Dimethyl Fumarate n = 233
Value	54.1

Population analysed: Safety Population (participants who received at least 1 dose of DMF, recorded in diary data)

Primary outcome: Duration of GI-related Episodes in DMF-treated Participants

Time frame: 12 Weeks. Median (Full Range). Unit: hours

Measure	Dimethyl Fumarate n = 128
Nausea; n=88	2.0 (1.81)
Diarrhea; n=78	1.6 (0.0 to 11.0)
Lower Abdominal Pain; n=67	2.0 (0.0 to 8.0)
Upper Abdominal Pain; n=66	1.8 (0.1 to 9.5)
Vomiting; n=27	0.4 (0.0 to 8.0)
Indigestion; n=52	1.9 (0.0 to 11.0)
Constipation; n=7	6.0 (0.0 to 23.0)
Bloating; n=41	3.0 (0.0 to 12.7)

Population analysed: Evaluable participants (treated participants who utilized symptomatic therapy during the overall treatment period \[12 weeks\]); n=number of participants with evaluable GI symptom specified.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: All serious adverse events (SAEs) from time of signed/dated informed consent through 12 weeks of treatment plus 4 weeks (± 5 days) post last dose.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dimethyl Fumarate	7 of 233 (3%)	0 of 233 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 26917993Fox 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Biogen

37 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing BG00012 (DMF) in people with Relapsing Forms of Multiple Sclerosis, run by Biogen at 37 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Worst Severity Score of Overall Gastrointestinal (GI) Events, Modified Overall GI Symptom Scale (MOGISS) (time frame: 12 Weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01873417, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2017.