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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-004562-22 | EudraCT Number |
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Sponsor decision
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard Treatment (One-Week Titration) | Active Comparator | 120 mg DMF twice daily for 1 week, then 240 mg (as 2 120-mg capsules) DMF twice daily for 11 weeks |
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| Slow Up-Titration (Six-Week Titration) | Experimental | 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 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| dimethyl fumarate | Drug | Participants will be dosed twice daily for 12 weeks. |
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| 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) | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Average Change From Baseline in GSRS Scores During DMF Treatment | 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. |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Biogen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Gilbert | Arizona | United States | |||
| Research Site |
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| ID | Title | Description |
|---|---|---|
| FG000 | Standard Treatment (One-Week Titration) | Following a 2-week placebo run-in baseline period, 120 mg dimethyl fumarate (DMF) twice daily for 1 week, then 240 mg (as 2 120-mg capsules) DMF twice daily for 11 weeks. |
| FG001 | Slow Up-Titration (Six-Week Titration) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Week 2 (Baseline), Week 14 |
| Time to First Worsening From Baseline in GSRS Score | 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 | 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 | 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 |
| Phoenix |
| Arizona |
| United States |
| Research Site | Long Beach | California | United States |
| Research Site | Miami | Florida | United States |
| Research Site | Avon | Indiana | United States |
| Research Site | Franklin | Indiana | United States |
| Research Site | Overland Park | Kansas | United States |
| Research Site | Lewiston | Maine | United States |
| Research Site | 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 | Cincinnati | Ohio | United States |
| Research Site | Dallas | Texas | United States |
| Research Site | Wenatchee | Washington | United States |
| Research Site | Leuven | Belgium |
| Research Site | Wilrijk | Belgium |
| Research Site | Prague | Czechia |
| Research Site | Merano | Bolzano | Italy |
| Research Site | Montichiari | Italy |
Following a 2-week placebo run-in baseline period, 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 two 120-mg capsules) DMF twice daily for 6 weeks. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Standard Treatment (One-Week Titration) | Following a 2-week placebo run-in baseline period, 120 mg DMF twice daily for 1 week, then 240 mg (as 2 120-mg capsules) DMF twice daily for 11 weeks. |
| BG001 | Slow Up-Titration (Six-Week Titration) | Following a 2-week placebo run-in baseline period, 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 two 120-mg capsules) DMF twice daily for 6 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Proportion of Participants With a Worsening in Severity of Gastrointestinal (GI) Adverse Events (AEs) on the Gastrointestinal Symptom Rating Scale (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. A higher score relative to Baseline indicates worsening of severity. | The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis. | Posted | from Week 2 (Baseline) to Week 14 |
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| Secondary | Average Change From Baseline in GSRS Scores During DMF Treatment | 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. | The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis. | Posted | Week 2 (Baseline), Week 14 |
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| Secondary | Time to First Worsening From Baseline in GSRS Score | 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. | The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis. | Posted | Week 2 (Baseline), Week 14 |
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| Secondary | Time to Recovery to Baseline From Last Occurrence of Worst GSRS Score | 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. | The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis. | Posted | Week 2 (Baseline), Week 14 |
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| Secondary | Average Change From Baseline in GSRS Scores to the End of Weeks 4, 6, 8, 10, 12, and 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. | The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis. | Posted | Week 2 (Baseline), Weeks 4, 6, 8, 10, 12, 14 |
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From start of study through Week 14 plus 2 weeks (±5 days) follow-up. Serious events were collected from time of informed consent and non-serious events were collected from the first dose and throughout the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Standard 1-Week Titration Arm | Following a 2-week placebo run-in baseline period, 120 mg DMF twice daily for 1 week, then 240 mg (as 2 120-mg capsules) DMF twice daily for 11 weeks. | 2 | 30 | 18 | 30 | ||
| EG001 | 6-Week Titration Arm | Following a 2-week placebo run-in baseline period, 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 two 120-mg capsules) DMF twice daily for 6 weeks. | 1 | 32 | 14 | 32 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal infection | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Hip fracture | Injury, poisoning and procedural complications | MedDRA 18.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
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| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Gastroenteritis viral | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
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| Multiple sclerosis relapse | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
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| Flushing | Vascular disorders | MedDRA 18.1 | Systematic Assessment |
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The Sponsor decided to terminate the study as a result of an evaluation of ongoing development programs.
Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Biogen Study Medical Director | Biogen | clinicaltrials@biogen.com |
| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000069462 | Dimethyl Fumarate |
| ID | Term |
|---|---|
| D005650 | Fumarates |
| D003998 | Dicarboxylic Acids |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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