Study of Oral Atogepant When Added to OnabotulinumtoxinA (BOTOX) to Assess Adverse Events and Change in Disease Activity in Adult Participants With Chronic Migraine

Study Overview
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Brief Summary
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Migraine is characterized by attacks of throbbing, moderate or severe headache, often associated with nausea, vomiting, and/or sensitivity to light and/or sound. The study will assess safety and tolerability of atogepant when added to BOTOX, as well as prospectively evaluate the efficacy of add-on atogepant for migraine prevention. Adverse events and change in disease activity will be monitored. Atogepant is an investigational drug being developed to prevent chronic migraine. Approximately 125 adult participants will be enrolled at approximately 30 sites in the United States. All participants will receive atogepant oral tablet once a day (QD) during the 24-week treatment period, in addition to their standard of care Botox. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Official Title
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A Phase 3 Multicenter 24-Week Open-Label Study to Evaluate the Safety, Tolerability, and Efficacy of Atogepant When Added to OnabotulinumtoxinA (BOTOX) for the Preventive Treatment of Chronic Migraine

Conditions
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Chronic Migraine

Intervention / Treatment
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* Drug: Atogepant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least a 1-year history of chronic migraine (CM), with or without aura, consistent with a diagnosis according to International Classification of Headache Disorders 3rd edition (ICHD-3 2018) and with or without acute medication overuse as defined in the protocol. Must be currently treated with BOTOX for CM: treated with >= 2 treatment cycles in the 8 months prior to Visit 2 (Day 1) with documentation of payer authorization to support continued use of BOTOX. Must have 8 to 23 (inclusive) migraine days in the electronic diary [eDiary] screening/baseline period (eDiary data must have been collected for at least 20 days). Exclusion Criteria: Use of opioid-containing products for more than 4 days for acute treatment of headache in the 3 months prior to Screening or during the screening/baseline period. Treatment of study target muscles using acupuncture, transcutaneous electrical nerve stimulation (TENS), cranial traction, dental splints for headache, or head and/or neck injections of anesthetics/steroids within 4 weeks prior to Screening. Concurrent use of any migraine prevention treatment other than BOTOX (required concomitant medication; or topiramate <100mg daily) including use of oral gepants in the 4 weeks prior to screening nor during the screening/baseline period. Current use or use within the 6 months (24 weeks) prior to Screening, of mAbs blocking the CGRP pathway. Concurrent use of oral gepants for acute migraine treatment in the 4 weeks prior to screening nor during the screening/baseline period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atogepant<br>Participants will receive atogepant once a day (QD) during the 24-week treatment period. | Drug: Atogepant<br>* Oral Tablet<br>* Other names: QULIPTA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. | Up to approximately 28 Weeks | 
| Responder Status of at least 25% Reduction in the Frequency of Monthly Migraine Days Collected via Daily Electronic Diary (eDiary) | Percentage of participants achieving at least 25% reduction from baseline in the frequency of monthly migraine days will be assessed. | Baseline (Week 0) through 24 Weeks | 
| Responder Status of at least 30% Reduction in the Frequency of Monthly Migraine Days Collected via eDiary | Percentage of participants achieving at least 30% reduction from baseline in the frequency of monthly migraine days will be assessed. | Baseline (Week 0) through 24 Weeks | 
| Responder Status of at least 50% Reduction in the Frequency of Monthly Migraine Days Collected via eDiary | Percentage of participants achieving at least 50% reduction from baseline in the frequency of monthly migraine days will be assessed. | Baseline (Week 0) through 24 Weeks | 
| Responder Status of at least 75% Reduction in the Frequency of Monthly Migraine Days Collected via eDiary | Percentage of participants achieving at least 75% reduction from baseline in the frequency of monthly migraine days will be assessed. | Baseline (Week 0) through 24 Weeks | 
| Responder Status of at least 100% Reduction in the Frequency of Monthly Migraine Days Collected via eDiary | Percentage of participants achieving at least 100% reduction from baseline in the frequency of monthly migraine days will be assessed. | Baseline (Week 0) through 24 Weeks | 
| Change From Baseline in Monthly Migraine Days | Change from Baseline in monthly migraine days, defined by International Headache Society (IHS) Guidelines 2018 will be assessed. | Baseline (Week 0) through 24 Weeks | 
| Change from Baseline in Monthly Headache Days, Moderate or Severe Headache Days, Cumulative Hours of Headache, Acute Treatment Medication Use Days, Headache Free Days, and Migraine Symptom-Free Days | Change from baseline in monthly headache days, moderate or severe headache days, cumulative hours of headache, acute treatment medication use days, headache free days, and migraine symptom-free days, defined by IHS Guidelines 2018 will be assessed. | Baseline (Week 0) through 24 Weeks | 
| Change from Baseline in Monthly days with Non-Headache Migraine Symptoms | Change from baseline in monthly days with non-headache migraine symptoms such as photophobia, phonophobia, nausea and/or vomiting, dizziness, neck pain, tiredness, mood change, yawning, thirst, cravings, urinary frequency, cranial autonomic symptoms | Baseline (Week 0) through 24 Weeks | 
| Change from Baseline in Monthly Activity Impairment in Migraine - Diary (AIM-D) | The AIM-D is an 11-item daily diary measure that assesses the impact of migraine and is comprised of two domains that evaluate performance of daily activities (7 items) and physical impairment (4 items). | Baseline (Week 0) through 24 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Migraine, Migraine, Atogepant, OnabotulinumtoxinA, BOTOX, QULIPTA