Episodic Migraine, Headache, Headache, Migraine, Migraine
Conditions
Keywords
Prescription digital therapeutic (PDT), Software as a Medical Device (SaMD), Smartphone app
Brief summary
Randomized study of two digital therapeutics for the prevention of episodic migraine
Detailed description
The purpose of this randomized ReMMi-D trial is to evaluate the effectiveness 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.
Interventions
DEVICEReMMi-D Digital Therapeutic
Evaluate the effectiveness 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.
Sponsors
Click Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A participant will be eligible for entry into the study if all of the following criteria are met: 1. Willing and able to provide written informed consent to participate in the study, attend study visits, and comply with study-related requirements and assessments. 2. Lives in the United States. 3. Adult or late adolescent, 18 years of age or older at the time of informed consent. 4. Fluent in written and spoken English, confirmed by ability to read and understand the informed consent form. 5. 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. 1. Age of onset of migraines prior to 50 years of age 2. Migraine attacks, on average, lasting 4-72 hours if untreated 3. 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) 4. Four to fourteen migraine days during the run-in period 6. Is currently managing migraines with ≥1 prescription acute treatment and/or prescription first or second-line preventive medications, as assessed by a physician. 7. 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. 8. Is willing and able to receive SMS text messages and push messages on their smartphone. 9. Is the owner of, and has regular access to, an email address. 10. 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: 1. History of basilar migraine or hemiplegic migraine. 2. Active chronic pain syndromes, such as fibromyalgia, chronic pelvic pain, or complex regional pain syndrome (CRPS). 3. 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. 4. 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. 5. 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. 6. Currently taking a prescription anti-calcitonin gene-related peptide (CGRP) for either episodic or chronic migraine. 7. Post-traumatic headache, persistent post-traumatic headache, or post-concussion syndrome. 8. 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. 9. 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. 10. Previous enrollment in any digital therapeutics pilot or pivotal study for a migraine indication. 11. Participation in any other investigational clinical study while participating in this clinical study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in MMD (Monthly Migraine Days) | Baseline (28-day Run-in Period) to Week 12 (previous 28 days, Week 9 through Week 12) | Change in the number of MMDs from baseline (28-day Run-in Period) to Week 12 (previous 28 days, Week 9 through Week 12). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Number of MMD Recorded Over the Previous 28 Days at Week 4 and Week 8 | Baseline (28-day Run-in Period) to Weeks 4 and 8 | Change from baseline (28-day Run-in Period) in the number of MMDs recorded over the previous 28 days at Week 4 and at Week 8 |
| Change From Baseline in the Mean Number of MMD Over 12 Weeks | Baseline (28-day Run-in Period) to Week 12 | Change from baseline (28-day Run-in Period) in the mean number of MMDs over 12 weeks. |
| Change in Number of Headaches With at Least Moderate Severity From Baseline to Week 12 | Baseline (28-day Run-in Period) to Week 12 (previous 28 days, Week 9 through Week 12) | Change in the number of headaches with at least moderate severity from baseline (28-day run-in period) to Week 12 (previous 28 days, Week 9 through Week 12). |
| Participants Who Have at Least a 50% Reduction From Baseline | Baseline (28-day Run-in Period) to Week 12 (previous 28 days, Week 9 through Week 12) | Participants who have at least a 50% reduction from baseline (28-day Run-in Period) in the number of MMDs to Week 12 (previous 28 days, Week 9 through Week 12) |
| Change From Baseline (28-day Run-in Period) in the Migraine Disability Assessment (MIDAS) to Week 12 (Previous 28 Days, Week 9 Through Week 12) | Baseline to Weeks 4, 8, and 12 | Change from baseline in the Migraine Disability Assessment (MIDAS) at Week 4, Week 8, and Week 12 The Migraine Disability Assessment (MIDAS) questionnaire is a brief, self report 5-item questionnaire (scale: 0 - 90 for each of 5 subscales) designed to quantify headache-related disability over a 3-month period. The 5 subscale scores are summed to compute the MIDAS total score (scale: 0 - 450). Lower scores indicate less headache-related disability. |
| Change From Baseline (28-day Run-in Period) to Week 12 (Previous 28 Days, Week 9 Through Week 12) in the Number of Migraines With Use of an Acute Migraine Medication | Baseline (28-day Run-in Period) to Week 12 (previous 28 days, Week 9 through Week 12) | Change in the number of migraines with use of an acute migraine medications from the run-in period to Weeks 9-12. The number of migraines with use of an acute medication will be counted for the run-in period and for post randomization period. The change from baseline will be calculated as number of migraines in weeks 9-12 minus number of migraines in the run-in period with use of an acute medication. |
| Change in the Number of Monthly Headache Days (MHDs) From Baseline to Week 12 | Baseline (28-day Run-in Period) to Week 12 (previous 28 days, Week 9 through Week 12) | Change in the number of monthly headache days from baseline to Weeks 9-12 |
| Change From Baseline in the Migraine-Specific Quality-of-Life Questionnaire v2.1 (MSQ) Total Score Over the Previous 28 Days at Week 4, Week 8, and Week 12 | Baseline (28-day Run-in Period) to Weeks 4, 8 and 12. | Change from baseline in the Migraine-Specific Quality-of-Life Questionnaire v2.1 (MSQ) at Week 4, Week 8, and Week 12 The MSQ is a self-administered, 14-item instrument that is completed at baseline, Week 4, Week 8, and Week 12. Participants respond to items using a 6-point scale: none of the time, a little bit of the time, some of the time, a good bit of the time, most of the time, and all of the time, which are assigned scores of 1 to 6, respectively. Next, raw dimension scores are computed as a sum of recoded item scores and rescaled from a 0 to 100 scale such that higher scores indicate better quality of life. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A (CT-132) Mobile application A (CT-132) as a software-based intervention for the preventive treatment of episodic migraine in late adolescents and adults. | 285 |
| Arm B (Digital Control) Mobile application B (Digital Control) is an investigational digital therapeutic that is being studied for the preventative treatment of episodic migraine. | 283 |
| Total | 568 |
Baseline characteristics
| Characteristic | Arm A (CT-132) | Total | Arm B (Digital Control) |
|---|---|---|---|
| Age, Continuous | 38.4 years STANDARD_DEVIATION 10.4 | 38.7 years STANDARD_DEVIATION 10.3 | 38.9 years STANDARD_DEVIATION 10.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 23 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 275 Participants | 545 Participants | 270 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 12 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 8 Participants | 20 Participants | 12 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 269 Participants | 530 Participants | 261 Participants |
| Region of Enrollment United States | 285 Participants | 568 Participants | 283 Participants |
| Sex/Gender, Customized Female | 263 Participants | 528 Participants | 265 Participants |
| Sex/Gender, Customized Male | 12 Participants | 25 Participants | 13 Participants |
| Sex/Gender, Customized Other | 10 Participants | 15 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 278 | 0 / 278 |
| other Total, other adverse events | 22 / 278 | 16 / 278 |
| serious Total, serious adverse events | 1 / 278 | 0 / 278 |
Outcome results
Primary
Change in MMD (Monthly Migraine Days)
Change in the number of MMDs from baseline (28-day Run-in Period) to Week 12 (previous 28 days, Week 9 through Week 12).
Time frame: Baseline (28-day Run-in Period) to Week 12 (previous 28 days, Week 9 through Week 12)
Population: Intent-to-treat Population, all enrolled participants who were randomized, based on the assigned intervention in the randomization and recorded in the database.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arm A (CT-132) | Change in MMD (Monthly Migraine Days) | -3.04 migraine days per month |
| Arm B (Digital Control) | Change in MMD (Monthly Migraine Days) | -2.14 migraine days per month |
Secondary
Change From Baseline (28-day Run-in Period) in the Migraine Disability Assessment (MIDAS) to Week 12 (Previous 28 Days, Week 9 Through Week 12)
Change from baseline in the Migraine Disability Assessment (MIDAS) at Week 4, Week 8, and Week 12 The Migraine Disability Assessment (MIDAS) questionnaire is a brief, self report 5-item questionnaire (scale: 0 - 90 for each of 5 subscales) designed to quantify headache-related disability over a 3-month period. The 5 subscale scores are summed to compute the MIDAS total score (scale: 0 - 450). Lower scores indicate less headache-related disability.
Time frame: Baseline to Weeks 4, 8, and 12
Population: The overall number of participant analyzed present the number of participant with data at the time interval the assessment was complete (at week 4, at week 8, and at week 12).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A (CT-132) | Change From Baseline (28-day Run-in Period) in the Migraine Disability Assessment (MIDAS) to Week 12 (Previous 28 Days, Week 9 Through Week 12) | Change from Baseline at Week 4 | -5.27 score on a scale | Standard Deviation 29.89 |
| Arm A (CT-132) | Change From Baseline (28-day Run-in Period) in the Migraine Disability Assessment (MIDAS) to Week 12 (Previous 28 Days, Week 9 Through Week 12) | Change from Baseline at Week 8 | -7.50 score on a scale | Standard Deviation 31.14 |
| Arm A (CT-132) | Change From Baseline (28-day Run-in Period) in the Migraine Disability Assessment (MIDAS) to Week 12 (Previous 28 Days, Week 9 Through Week 12) | Change from Baseline at Week 12 | -10.55 score on a scale | Standard Deviation 33.03 |
| Arm B (Digital Control) | Change From Baseline (28-day Run-in Period) in the Migraine Disability Assessment (MIDAS) to Week 12 (Previous 28 Days, Week 9 Through Week 12) | Change from Baseline at Week 4 | -0.89 score on a scale | Standard Deviation 30.31 |
| Arm B (Digital Control) | Change From Baseline (28-day Run-in Period) in the Migraine Disability Assessment (MIDAS) to Week 12 (Previous 28 Days, Week 9 Through Week 12) | Change from Baseline at Week 8 | -0.85 score on a scale | Standard Deviation 33.27 |
| Arm B (Digital Control) | Change From Baseline (28-day Run-in Period) in the Migraine Disability Assessment (MIDAS) to Week 12 (Previous 28 Days, Week 9 Through Week 12) | Change from Baseline at Week 12 | -3.30 score on a scale | Standard Deviation 29.52 |
Secondary
Change From Baseline (28-day Run-in Period) to Week 12 (Previous 28 Days, Week 9 Through Week 12) in the Number of Migraines With Use of an Acute Migraine Medication
Change in the number of migraines with use of an acute migraine medications from the run-in period to Weeks 9-12. The number of migraines with use of an acute medication will be counted for the run-in period and for post randomization period. The change from baseline will be calculated as number of migraines in weeks 9-12 minus number of migraines in the run-in period with use of an acute medication.
Time frame: Baseline (28-day Run-in Period) to Week 12 (previous 28 days, Week 9 through Week 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A (CT-132) | Change From Baseline (28-day Run-in Period) to Week 12 (Previous 28 Days, Week 9 Through Week 12) in the Number of Migraines With Use of an Acute Migraine Medication | -2.70 migraine | Standard Deviation 2.38 |
| Arm B (Digital Control) | Change From Baseline (28-day Run-in Period) to Week 12 (Previous 28 Days, Week 9 Through Week 12) in the Number of Migraines With Use of an Acute Migraine Medication | -2.50 migraine | Standard Deviation 2.42 |
Secondary
Change From Baseline in the Mean Number of MMD Over 12 Weeks
Change from baseline (28-day Run-in Period) in the mean number of MMDs over 12 weeks.
Time frame: Baseline (28-day Run-in Period) to Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A (CT-132) | Change From Baseline in the Mean Number of MMD Over 12 Weeks | -3.35 migraine days per month | Standard Deviation 3.63 |
| Arm B (Digital Control) | Change From Baseline in the Mean Number of MMD Over 12 Weeks | -2.26 migraine days per month | Standard Deviation 3.67 |
Secondary
Change From Baseline in the Migraine-Specific Quality-of-Life Questionnaire v2.1 (MSQ) Total Score Over the Previous 28 Days at Week 4, Week 8, and Week 12
Change from baseline in the Migraine-Specific Quality-of-Life Questionnaire v2.1 (MSQ) at Week 4, Week 8, and Week 12 The MSQ is a self-administered, 14-item instrument that is completed at baseline, Week 4, Week 8, and Week 12. Participants respond to items using a 6-point scale: none of the time, a little bit of the time, some of the time, a good bit of the time, most of the time, and all of the time, which are assigned scores of 1 to 6, respectively. Next, raw dimension scores are computed as a sum of recoded item scores and rescaled from a 0 to 100 scale such that higher scores indicate better quality of life.
Time frame: Baseline (28-day Run-in Period) to Weeks 4, 8 and 12.
Population: The overall number of participant analyzed present the number of participant with data at the time-interval the assessment was complete (at week 4, at week 8 and at week 12).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A (CT-132) | Change From Baseline in the Migraine-Specific Quality-of-Life Questionnaire v2.1 (MSQ) Total Score Over the Previous 28 Days at Week 4, Week 8, and Week 12 | Change from Baseline to Week 4 | 6.16 score on a scale | Standard Deviation 13.48 |
| Arm A (CT-132) | Change From Baseline in the Migraine-Specific Quality-of-Life Questionnaire v2.1 (MSQ) Total Score Over the Previous 28 Days at Week 4, Week 8, and Week 12 | Change from Baseline to Week 8 | 9.13 score on a scale | Standard Deviation 15.82 |
| Arm A (CT-132) | Change From Baseline in the Migraine-Specific Quality-of-Life Questionnaire v2.1 (MSQ) Total Score Over the Previous 28 Days at Week 4, Week 8, and Week 12 | Change from Baseline to Week 12 | 11.95 score on a scale | Standard Deviation 15.52 |
| Arm B (Digital Control) | Change From Baseline in the Migraine-Specific Quality-of-Life Questionnaire v2.1 (MSQ) Total Score Over the Previous 28 Days at Week 4, Week 8, and Week 12 | Change from Baseline to Week 4 | 2.12 score on a scale | Standard Deviation 13.42 |
| Arm B (Digital Control) | Change From Baseline in the Migraine-Specific Quality-of-Life Questionnaire v2.1 (MSQ) Total Score Over the Previous 28 Days at Week 4, Week 8, and Week 12 | Change from Baseline to Week 8 | 4.30 score on a scale | Standard Deviation 13.85 |
| Arm B (Digital Control) | Change From Baseline in the Migraine-Specific Quality-of-Life Questionnaire v2.1 (MSQ) Total Score Over the Previous 28 Days at Week 4, Week 8, and Week 12 | Change from Baseline to Week 12 | 5.03 score on a scale | Standard Deviation 16.26 |
Secondary
Change From Baseline in the Number of MMD Recorded Over the Previous 28 Days at Week 4 and Week 8
Change from baseline (28-day Run-in Period) in the number of MMDs recorded over the previous 28 days at Week 4 and at Week 8
Time frame: Baseline (28-day Run-in Period) to Weeks 4 and 8
Population: The overall number of participant analyzed present the number of participant with data at the time interval the assessment was complete (at week 4 and at week 8).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A (CT-132) | Change From Baseline in the Number of MMD Recorded Over the Previous 28 Days at Week 4 and Week 8 | Change from Baseline at Week 4 | -1.58 migraine days per month | Standard Deviation 3.55 |
| Arm A (CT-132) | Change From Baseline in the Number of MMD Recorded Over the Previous 28 Days at Week 4 and Week 8 | Change from Baseline at Week 8 | -2.24 migraine days per month | Standard Deviation 3.92 |
| Arm B (Digital Control) | Change From Baseline in the Number of MMD Recorded Over the Previous 28 Days at Week 4 and Week 8 | Change from Baseline at Week 4 | -1.20 migraine days per month | Standard Deviation 3.31 |
| Arm B (Digital Control) | Change From Baseline in the Number of MMD Recorded Over the Previous 28 Days at Week 4 and Week 8 | Change from Baseline at Week 8 | -1.87 migraine days per month | Standard Deviation 3.65 |
Secondary
Change in Number of Headaches With at Least Moderate Severity From Baseline to Week 12
Change in the number of headaches with at least moderate severity from baseline (28-day run-in period) to Week 12 (previous 28 days, Week 9 through Week 12).
Time frame: Baseline (28-day Run-in Period) to Week 12 (previous 28 days, Week 9 through Week 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A (CT-132) | Change in Number of Headaches With at Least Moderate Severity From Baseline to Week 12 | -3.48 headaches | Standard Deviation 2.66 |
| Arm B (Digital Control) | Change in Number of Headaches With at Least Moderate Severity From Baseline to Week 12 | -2.87 headaches | Standard Deviation 2.64 |
Secondary
Change in the Number of Monthly Headache Days (MHDs) From Baseline to Week 12
Change in the number of monthly headache days from baseline to Weeks 9-12
Time frame: Baseline (28-day Run-in Period) to Week 12 (previous 28 days, Week 9 through Week 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A (CT-132) | Change in the Number of Monthly Headache Days (MHDs) From Baseline to Week 12 | -4.86 headache days per month | Standard Deviation 4.29 |
| Arm B (Digital Control) | Change in the Number of Monthly Headache Days (MHDs) From Baseline to Week 12 | -3.69 headache days per month | Standard Deviation 4.08 |
Secondary
Participants Who Have at Least a 50% Reduction From Baseline
Participants who have at least a 50% reduction from baseline (28-day Run-in Period) in the number of MMDs to Week 12 (previous 28 days, Week 9 through Week 12)
Time frame: Baseline (28-day Run-in Period) to Week 12 (previous 28 days, Week 9 through Week 12)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A (CT-132) | Participants Who Have at Least a 50% Reduction From Baseline | Responder | 141 Participants |
| Arm A (CT-132) | Participants Who Have at Least a 50% Reduction From Baseline | Non-responder | 125 Participants |
| Arm B (Digital Control) | Participants Who Have at Least a 50% Reduction From Baseline | Responder | 113 Participants |
| Arm B (Digital Control) | Participants Who Have at Least a 50% Reduction From Baseline | Non-responder | 151 Participants |