Study of Two Digital Therapeutics for the Prevention of Episodic Migraine

Study Overview
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Brief Summary
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Randomized study of two digital therapeutics for the prevention of episodic migraine

Detailed Description
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The purpose of this randomized ReMMi-D trial is to evaluate the efficacy and safety of two prescription mobile applications that provide an interactive, software-based intervention for the preventative treatment of episodic migraine in late adolescents and adults.

Official Title
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A Randomized Double-blind, Parallel-Group, Virtual Study to Evaluate the Efficacy and Safety of Two Digital Therapeutics in Late Adolescents and Adults for the Prevention of Episodic Migraine

Conditions
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Migraine, Episodic Migraine, Headache, Headache, Migraine

Intervention / Treatment
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* Device: ReMMi-D Digital Therapeutic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A participant will be eligible for entry into the study if all of the following criteria are met: Willing and able to provide written informed consent to participate in the study, attend study visits, and comply with study-related requirements and assessments. Lives in the United States. Adult or late adolescent, 18 years of age or older at the time of informed consent. Fluent in written and spoken English, confirmed by ability to read and understand the informed consent form. The following will be physician-reviewed: Participant has at least a 1-year history of migraine (with or without aura) consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd Edition. Age of onset of migraines prior to 50 years of age Migraine attacks, on average, lasting 4-72 hours if untreated Per participant report, 4-14 migraine days per month within the last 3 months prior to the Screening Visit (a month is defined as 28 days) Four to fourteen migraine days during the run-in period Is currently managing migraines with ≥1 prescription acute treatment and/or prescription first or second-line preventive medications, as assessed by a physician. Is the sole user of an iPhone with an iPhone operating system (iOS) 14 or later or a smartphone with an Android operating system (OS) 11 or later and is willing to download and use the Study App required by the protocol. Is willing and able to receive SMS text messages and push messages on their smartphone. Is the owner of, and has regular access to, an email address. Has regular access to the Internet via cellular data plan and/or wifi. Exclusion Criteria: A participant will not be eligible for study entry if any of the following criteria are met: History of basilar migraine or hemiplegic migraine. Active chronic pain syndromes, such as fibromyalgia, chronic pelvic pain, or complex regional pain syndrome (CRPS). Other pain syndromes (including trigeminal neuralgia), psychiatric conditions (such as major depressive episode, bipolar disorder, major depressive disorder, schizophrenia), dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion, might interfere with study assessments. History of, treatment for, or evidence of, alcohol or drug abuse within the past 12 months (48 weeks) or having met DSM-V criteria for any significant substance use disorder within the past 12 months (48 weeks) from the date of the screening visit. History of use of analgesics (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs] or acetaminophen, including opioids) or butalbital on ≥ 15 days per month during the 3 months (12 weeks) prior to the Screening Visit or during the run-in period. Currently taking a prescription anti-calcitonin gene-related peptide (CGRP) for either episodic or chronic migraine. Post-traumatic headache, persistent post-traumatic headache, or post-concussion syndrome. Other significant episodic or chronic medical condition(s) that in the opinion of the Investigator, may confound the interpretation of findings to inform PDT development. Failure to adhere with or inability to complete Study App inputs and onboarding activities during the run-in period. Participants who are not adherent during the run-in period are not eligible for study entry. Previous enrollment in any digital therapeutics pilot or pivotal study for a migraine indication. Participation in any other investigational clinical study while participating in this clinical study.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Mobile application A as a software-based intervention for the preventive treatment of episodic migraine in late adolescents and adults. | Device: ReMMi-D Digital Therapeutic<br>* Evaluate the efficacy and safety of prescription mobile applications that provide an interactive, software-based intervention for the preventative treatment of episodic migraine in late adults and adolescents.<br>|
| Experimental: Arm B<br>Mobile application B is an investigational digital therapeutic that is being studied for the preventative treatment of episodic migraine. | Device: ReMMi-D Digital Therapeutic<br>* Evaluate the efficacy and safety of prescription mobile applications that provide an interactive, software-based intervention for the preventative treatment of episodic migraine in late adults and adolescents.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in MMD (monthly migraine days) | Change from baseline in the number of Monthly Migraine Days (MMD) at Week 12 of intervention | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients with Decrease in MMD | Proportion of participants who have at least a 50% reduction from baseline in the mean number of MMD at Week 12 | Baseline to Week 12 | 
| Decrease in MMD | Change from baseline in the number of MMD recorded over the previous 28 days at Week 4 and Week 8 | Baseline to Weeks 4 and 8 | 
| Decrease in MMD | Change from baseline in the mean number of MMD over 12 weeks | Baseline to Week 12 | 
| Change in average headache severity | Change in the average severity of headache from the run-in period to Weeks 9-12 assessed by Likert-type scale of 1-3 in severity | Run-in to Weeks 9-12 | 
| Change in MSQ | Change from baseline in the Migraine-Specific Quality-of-Life Questionnaire v2.1 (MSQ) at Week 4, Week 8, and Week 12 | Baseline to Weeks 4, 8 and 12 | 
| Change in MIDAS | Change from baseline in the Migraine Disability Assessment (MIDAS) at Week 4, Week 8, and Week 12 | Baseline to Weeks 4, 8, and 12 | 
| Change in frequency of Migraine Medications | Change in the frequency used of acute migraine medications from the run-in period to Weeks 9-12 | Run-in to Weeks 9-12 | 
| Change in dose of Migraine Medications | Change in the dose of acute migraine medications from the run-in period to Weeks 9-12 | Run-in to Weeks 9-12 | 
| Change in type of Migraine Medications | Change in the type of acute migraine medications from the run-in period to Weeks 9-12 | Run-in to Weeks 9-12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prescription digital therapeutic (PDT), Software as a Medical Device (SaMD), Smartphone app