Tecfidera Slow-Titration Study (TITRATION)

March 27, 2017 updated by: Biogen

A Multicenter, Treatment-Blind Phase 3b Study to Evaluate Whether 6-Week Up-Titration in Tecfidera® Dose is Effective in Reducing the Incidence of Gastrointestinal Adverse Events in Patients With Multiple Sclerosis

The primary objective of the study is to assess whether a 6-week titration (compared with a 1-week titration) is effective in reducing the incidence of dimethyl fumarate (DMF [Tecfidera])-related gastrointestinal (GI) adverse events (AEs) in participants with multiple sclerosis (MS). The secondary objective of this study is to assess whether a 6-week titration (compared with a 1-week titration) is effective in reducing the average severity and duration of GI symptoms over 12 weeks of DMF treatment in this study population.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
62

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium
        • Research Site
      • Wilrijk, Belgium
        • Research Site
  • Czech Republic
      • Prague, Czech Republic
        • Research Site
  • Italy
      • Montichiari, Italy
        • Research Site
    • Bolzano
      • Merano, Bolzano, Italy
        • Research Site
  • United States
    • Arizona
      • Gilbert, Arizona, United States
        • Research Site
      • Phoenix, Arizona, United States
        • Research Site
    • California
      • Long Beach, California, United States
        • Research Site
    • Florida
      • Miami, Florida, United States
        • Research Site
    • Indiana
      • Avon, Indiana, United States
        • Research Site
      • Franklin, Indiana, United States
        • Research Site
    • Kansas
      • Overland Park, Kansas, United States
        • Research Site
    • Maine
      • Lewiston, Maine, United States
        • Research Site
    • North Carolina
      • Asheville, North Carolina, United States
        • Research Site
      • Cary, North Carolina, United States
        • Research Site
      • Charlotte, North Carolina, United States
        • Research Site
      • Wilmington, North Carolina, United States
        • Research Site
    • Ohio
      • Cincinnati, Ohio, United States
        • Research Site
    • Texas
      • Dallas, Texas, United States
        • Research Site
    • Washington
      • Wenatchee, Washington, United States
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  • Diagnosis of MS consistent with locally labeled indication for DMF
  • No prior treatment with DMF
  • Female subjects of childbearing potential who are not surgically sterile and male subjects must practice effective contraception during their participation in the study
  • Have had a recent complete blood count (CBC), including lymphocyte count, that does not preclude participation in the study, in the judgement of the investigator

Key Exclusion Criteria:

  • Have a recent history or ongoing GI illness (e.g., peptic ulcer, irritable bowel syndrome) or any other current condition with GI signs and symptoms (e.g., nausea, vomiting, abdominal pain, or diarrhea) that may interfere with assessment of study endpoints
  • Have other major comorbid conditions that preclude participation in the study, as determined by the investigator
  • Participant is pregnant, breastfeeding, or planning a pregnancy during the study period
  • Are receiving concomitant disease-modifying therapies for MS including, but not limited to, natalizumab, interferon beta, glatiramer acetate, fingolimod, alemtuzumab, teriflunomide, or laquinimod at screening
  • History of severe allergic or anaphylactic reactions or known drug hypersensitivity
  • NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Standard Treatment (One-Week Titration)
120 mg DMF twice daily for 1 week, then 240 mg (as 2 120-mg capsules) DMF twice daily for 11 weeks
Drug: dimethyl fumarate
Participants will be dosed twice daily for 12 weeks.
Other Names:
  • BG00012
  • DMF
  • Tecfidera
Experimental: Slow Up-Titration (Six-Week Titration)
120 mg DMF once daily (morning dose) and placebo once daily (evening dose) for 2 weeks, then 120 mg DMF twice daily for 2 weeks, then 240 mg (as 2 120-mg capsules) DMF in the morning and 120 mg in the evening for 2 weeks, then 240 mg (as 2 120-mg capsules) DMF twice daily for 6 weeks
Drug: dimethyl fumarate
Participants will be dosed twice daily for 12 weeks.
Other Names:
  • BG00012
  • DMF
  • Tecfidera

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Proportion of Participants With a Worsening in Severity of Gastrointestinal (GI) Adverse Events (AEs) on the Gastrointestinal Symptom Rating Scale (GSRS)
Time Frame: from Week 2 (Baseline) to Week 14
The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms. A higher score relative to Baseline indicates worsening of severity.
from Week 2 (Baseline) to Week 14

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Average Change From Baseline in GSRS Scores During DMF Treatment
Time Frame: Week 2 (Baseline), Week 14
Average change from baseline in GSRS scores over the 12 weeks of DMF treatment as measured by the total change in GSRS scores from baseline divided by the total number of days with GSRS scores recorded. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms.
Week 2 (Baseline), Week 14
Time to First Worsening From Baseline in GSRS Score
Time Frame: Week 2 (Baseline), Week 14
The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms. A higher score relative to Baseline indicates worsening of severity.
Week 2 (Baseline), Week 14
Time to Recovery to Baseline From Last Occurrence of Worst GSRS Score
Time Frame: Week 2 (Baseline), Week 14
The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms. A higher score relative to Baseline indicates worsening of severity.
Week 2 (Baseline), Week 14
Average Change From Baseline in GSRS Scores to the End of Weeks 4, 6, 8, 10, 12, and 14
Time Frame: Week 2 (Baseline), Weeks 4, 6, 8, 10, 12, 14
Average change from baseline to end of DMF treatment in the GSRS. The GSRS is a weekly recall scale to rate the severity of GI symptoms in participants. It was modified for daily recall in this study. GSRS is a rating scale consisting of 15 items for assessment of GI symptoms (see Appendix 1). Items are scored for intensity on a 7-grade Likert scale, defined by descriptive anchors such that 0 = none, 1 = minor, 2 = mild, 3 =moderate, 4 = moderately severe, 5 = severe, and 6 = very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 0 to 6; a score of 0 indicates that no symptoms are present, and a score of 6 indicates the worst possible degree of all symptoms.
Week 2 (Baseline), Weeks 4, 6, 8, 10, 12, 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Biogen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 23, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 23, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 28, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 5, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 27, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 109MS416
  • 2014-004562-22 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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