Relapsing Remitting Multiple Sclerosis
Conditions
Brief summary
Single site, open label, randomized design in patients with relapsing forms of Multiple Sclerosis. At the Screening Visit, the patient will be given a diary containing the MAGIS scale to be completed once a day for the first two weeks while on Dimethyl Fumarate (DMF), including the titration period. After two weeks or if a patient experiences 3 or more consecutive days of GI symptoms in any category of ≥3.5, the patient will return for a Baseline Visit. The MAGIS diary will be reviewed by the coordinator. Any patient who has reported an average MAGIS score of greater than or equal to 3.5 in at least one of the key categories will be randomized to a standard therapy or treatment arm. Patients who report a MAGIS of less than 3.5 during this period will be terminated from the study at this visit. Patients with an average reported MAGIS of greater than 6.5 at Baseline will be placed in the treatment arm. Patients who are randomized to the treatment arm will be instructed to take 125 mg simethicone and one tablespoon of a high fat food (peanut butter) 10 minutes prior to each DMF dose. If the average MAGIS score is greater than 3.5 in the diarrhea category they will also be instructed to take 2 mg loperamide three times daily. Patients randomized to the standard therapy arm will be instructed to follow the normal dosing regimen for DMF with a food bolus of their choice prior to dosing. If severe symptoms (MAGIS \>6.5) are noted at any time post randomization in any MAGIS category, crossover to the treatment arm will be allowed. Both groups will be asked to rate their GI symptoms over the past 24 hours using the MAGIS scale once daily. Both treatment arms will be observed for 6 weeks. MAGIS will be recorded once daily. Patients will return to the clinic at Week 3 and Week 6/End of Treatment for diary and compliance review. After Week 6, patients will be instructed to return to a standard therapy. MAGIS will be recorded for one more week and collected at Week 7/End of Study.
Interventions
Sponsors
Biogen
Rocky Mountain MS Research Group, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Decision to treat with DMF must precede enrollment 2. Ability to understand the purpose and risk of the study and provide authorization for the use of protected health information in accordance with the monitoring agency 3. Men or women 18 years of age or older at the time of informed consent 4. Naïve to DMF or fumaric acid esters 5. Confirmed diagnosis of a relapsing form of multiple sclerosis as verified by the Principal Investigator
Exclusion criteria
1. Unable to unwilling to comply with study requirements as outlined in the informed consent 2. Known active malignancies or any other major comorbidities that, in the opinion of the Investigator, would affect the outcome of the study 3. Pregnant or breastfeeding or likely to become pregnant during the course of the study. Women of child-bearing potential must practice an acceptable form of birth control 4. Previous treatment with dimethyl fumarate 5. Past history of GI malignancy, gastric ulceration refractory to medical resolution, history of gastrectomy. At the discretion of the PI, resolved GI ulceration, gastroesophageal reflux will not be exclusionary 6. Known sensitivity or allergic reaction to peanuts, simethicone, or loperamide
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reported GI Symptoms | 7 Weeks | The primary endpoint will be severity of GI events as measured by the MAGIS scale for subjects in the treatment arm compared to the standard therapy arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Diarrhea Reduction | 7 Weeks | The secondary objective is to assess the reduction in diarrhea in the treatment group compared to the control. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Pre-Existing GI Conditions | 7 Weeks | The tertiary objective is to gather further data regarding pre-existing conditions (GE reflex, gastric bypass, stomach ulcer, etc) and their possible relationship to GI symptoms when initiating DMF. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Group Patients randomized to the standard therapy arm will be instructed to follow the normal dosing regimen for DMF with a food bolus of their choice prior to dosing. If severe symptoms (MAGIS \>6.5) are noted at any time post randomization in any MAGIS category, crossover to the treatment arm will be allowed. Both groups will be asked to rate their GI symptoms over the past 24 hours using the MAGIS scale once daily. | 1 |
| Treatment Arm Patients who are randomized to the treatment arm will be instructed to take 125 mg simethicone and one tablespoon of a high fat food (peanut butter)10 minutes prior to each DMF dose. If the average MAGIS score is greater than 3.5 in the diarrhea category they will also be instructed to take 2 mg loperamide three times daily.
Simethicone
Loperamide
Peanut Butter | 4 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Trial discontinued | 1 | 0 |
Baseline characteristics
| Characteristic | Control Group | Treatment Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 4 Participants | 5 Participants |
| Region of Enrollment United States | 1 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 4 |
| serious Total, serious adverse events | 0 / 1 | 0 / 4 |
Outcome results
Primary
Reported GI Symptoms
The primary endpoint will be severity of GI events as measured by the MAGIS scale for subjects in the treatment arm compared to the standard therapy arm.
Time frame: 7 Weeks
Population: Trial was shut down early as not enough patients qualified with GI symptoms their first 2 weeks after initiating DMF therapy
| Arm | Measure | Value |
|---|---|---|
| Control Group | Reported GI Symptoms | 0 |
| Treatment Arm | Reported GI Symptoms | 0 |
Secondary
Diarrhea Reduction
The secondary objective is to assess the reduction in diarrhea in the treatment group compared to the control.
Time frame: 7 Weeks
Population: Not enough patients qualified and the study was terminated early.
| Arm | Measure | Value |
|---|---|---|
| Control Group | Diarrhea Reduction | 0 |
| Treatment Arm | Diarrhea Reduction | 0 |
Other Pre-specified
Number of Participants With Pre-Existing GI Conditions
The tertiary objective is to gather further data regarding pre-existing conditions (GE reflex, gastric bypass, stomach ulcer, etc) and their possible relationship to GI symptoms when initiating DMF.
Time frame: 7 Weeks