Study to Evaluate Whether a Medication Event Monitoring System (MEMS) Can Improve Adherence to Tecfidera Treatment in Multiple Sclerosis Patients.

Study Overview
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Brief Summary
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The primary objective of the study is to determine whether a Medication Event Monitoring System (MEMS®) cap with a liquid crystal display (LCD) reader (a smart cap) along with additional patient counseling intervention (Arm 3) can improve adherence to dimethyl fumarate (DMF) treatment in Multiple Sclerosis (MS) patients as compared to a MEMS cap without an LCD reader (a standard cap) and no patient counseling intervention (standard of care, Arm 1) at Month 12. The secondary objectives of this study in this study population are: to determine if data display on a smart MEMS cap with an LCD reader (Arm 2) can improve adherence as compared to a standard MEMS cap without an LCD reader (Arm 1) at Month 12; to determine whether the addition of patient counseling intervention based on MEMS data (Arm 3), or data display from a MEMS cap with an LCD reader (Arm 2) can improve adherence compared to standard MEMS cap without an LCD reader (Arm 1) at Month 6; to assess persistence and compliance at Months 6 and 12 for all arms; to assess the association between adherence and patient- reported outcomes (PROs) for all arms including Multiple Sclerosis Impact Scale (MSIS-29), and the Work Productivity and Activity Impairment Questionnaire (WPAI): MS v2.0.

Official Title
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A Multicenter, Open-label Phase IV Study to Evaluate Whether a Medication Event Monitoring System (MEMS®) Can Improve Adherence to Tecfidera® (Delayed-release Dimethyl Fumarate) Treatment in Multiple Sclerosis Patients.

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: dimethyl fumarate
* Device: Medication Event Monitoring System (MEMS)
* Behavioral: Adherence counseling


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: The candidate is a DMF-naïve patient Have a diagnosis of relapsing forms of MS and satisfy the approved therapeutic indication for DMF Have a recent (i.e., within the previous 6 months) complete blood count with results that do not preclude the patient's participation in the study, in the judgment of the Investigator Key Exclusion Criteria: Have comorbid conditions that preclude participation in the study, as determined by the Investigator History of severe allergic or anaphylactic reactions or known drug hypersensitivity Are participating, planning to participate, or have participated in the Tecfidera QuickStart Program NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Standard MEMS Cap<br>A standard MEMS cap that records the time and date when the bottle is opened without a visual LCD reader. Standard-of-care commercial supply of DMF (BID oral capsule) will be used in this study. | Drug: dimethyl fumarate<br>* 120 mg and 240 mg delayed release capsules<br>* Other names: BG000012;Device: Medication Event Monitoring System (MEMS)<br>* The MEMS automatically compiles drug dosing history data by electronically recording the date and time of each opening of the medication container<br>|
| Experimental: Arm 2: Smart MEMS Cap<br>A smart MEMS cap with feedback (an LCD reader that allows the participant to monitor DMF bottle openings). Standard-of-care commercial supply of DMF (BID oral capsule) will be used in this study. | Drug: dimethyl fumarate<br>* 120 mg and 240 mg delayed release capsules<br>* Other names: BG000012;Device: Medication Event Monitoring System (MEMS)<br>* The MEMS automatically compiles drug dosing history data by electronically recording the date and time of each opening of the medication container<br>|
| Experimental: Arm 3: Smart MEMS Cap + Counseling<br>A smart MEMS cap with feedback (an LCD reader that allows the participant to monitor DMF bottle openings) and an adherence counseling intervention. Standard-of-care commercial supply of DMF (BID oral capsule) will be used in this study. | Drug: dimethyl fumarate<br>* 120 mg and 240 mg delayed release capsules<br>* Other names: BG000012;Device: Medication Event Monitoring System (MEMS)<br>* The MEMS automatically compiles drug dosing history data by electronically recording the date and time of each opening of the medication container<br>Behavioral: Adherence counseling<br>* A telephone call to discuss adherence and individualized strategies based on data collected via smart device (i.e., LCD reader)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Adherence Rates at Month 12: Arm 3 vs. Arm 1 | Adherence is defined as the proportion of time on treatment over the study observation time period, times the proportion of actual DMF doses taken per label according to feedback from MEMS data over the total expected DMF doses per label during a treatment period. | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Adherence Rates at Month 12: Arm 2 vs. Arm 1 | Adherence is defined as the proportion of time on treatment over the study observation time period, times the proportion of actual DMF doses taken per label according to feedback from MEMS data over the total expected DMF doses per label during a treatment period. | Month 12 | 
| Overall Adherence Rates at Month 6: Arm 3 vs. Arm 1 | Adherence is defined as the proportion of time on treatment over the study observation time period, times the proportion of actual DMF doses taken per label according to feedback from MEMS data over the total expected DMF doses per label during a treatment period. | Month 6 | 
| Overall Adherence Rates at Month 6: Arm 2 vs. Arm 1 | Adherence is defined as the proportion of time on treatment over the study observation time period, times the proportion of actual DMF doses taken per label according to feedback from MEMS data over the total expected DMF doses per label during a treatment period. | Month 6 | 
| Persistence Rates at Months 6 and 12 | Persistence rates defined as the proportion of time on treatment over the study observation time period. | Month 6, Month 12 | 
| Compliance Rates at Month 6 and 12 | Compliance rates defined as the proportion of actual DMF doses taken per label according to feedback from MEMS data over total expected DMF doses per label during treatment period. | Month 6, Month 12 | 
| Multiple Sclerosis Impact Scale (MSIS-29) | The 29-item MSIS-29 is a participant-reported outcome measure to assess the impact of MS on day-to-day life during the past 2 weeks from a participants perspective; it measures 20 physical items and 9 psychological items. The physical score is generated by summing individual items and then transforming to a scale with a range of 0 to 100, where high scores indicate worse health. | Month 6, Month 12 | 
| Work Productivity and Activity Impairment Questionnaire (WPAI: MS Version 2.0) | The WPAI questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (work time missed) 2. Presenteesism (impairment at work / reduced on-the-job effectiveness) 3. Work productivity loss (overall work impairment / absenteeism plus presenteeism) 4. Activity Impairment. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. | Month 6, Month 12 |