A Study to Evaluate the Efficacy and Safety of Oral Zavegepant in Migraine Prevention

Study Overview
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Brief Summary
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The purpose of this is study is to compare the efficacy of BHV-3500 (zavegepant) to placebo as a preventive treatment for migraine, as measured by the reduction in the number of migraine days per month.

Official Title
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A Phase 2/3 Randomized, Double-Blind, Placebo- Controlled Study to Evaluate the Efficacy and Safety of Oral Zavegepant in Migraine Prevention

Conditions
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Migraine

Intervention / Treatment
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* Drug: BHV-3500 (zavegepant)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has at least 1 year history of migraine (with or without aura) consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd Edition, including the following: Age of onset of migraines prior to 50 years of age Migraine attacks, on average, lasting 4 - 72 hours if untreated Per subject report, at least 15 headache days per month, at lest 8 migraine days per month, and at least 1 headache-free day per month within the last 3 months prior to the Screening Visit Eight or more migraine days during the Observation Period 15 or more headache days during the Observation Period One or more non-headache days during the Observation Period Ability to distinguish migraine attacks from tension/cluster headaches Subjects on prophylactic migraine medication are permitted to remain on 1 medication with possible migraine-prophylactic effects if the dose has been stable for at least 3 months prior to the Screening Visit, and the dose is not expected to change during the course of the study. Exclusion Criteria: Subject with a history of HIV disease Subject history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. Subjects with Myocardial Infarction (MI), Acute Coronary Syndrome (ACS), Percutaneous Coronary Intervention (PCI), cardiac surgery, stroke or transient ischemic attack (TIA) during the 6 months prior to screening Uncontrolled hypertension (high blood pressure), or uncontrolled diabetes (however subjects can be included who have stable hypertension and/or diabetes for at least 3 months prior to screening). Subjects with major depressive episode or anxiety disorder which require more than 1 daily medication for each disorder or subjects with a major depressive episode within the last 12 months. Medications to treat major depressive disorder or an anxiety disorder must have been at a stable dose for at least 3 months prior to the Screening Visit. Subjects with active chronic pain syndromes, other pain syndromes (including trigeminal neuralgia), psychiatric conditions, dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion interfere with study assessments of safety or efficacy. Subject has a history of gastric, or small intestinal surgery (including Gastric Bypass, Gastric Banding, Gastric Sleeve, Gastric Balloon, etc.), or has disease or condition (e.g. chronic pancreatitis, ulcerative colitis, etc.) that causes malabsorption. Body mass index > 33 kg/m2 History of gallstones or cholecystectomy. The subject has a history or current evidence of any unstable medical conditions (e.g., history of congenital heart disease or arrhythmia, known or suspected infection, hepatitis B or C, or cancer) that, in the investigator's opinion, would expose them to undue risk of a significant adverse event (AE) or interfere with assessments of safety or efficacy during the course of the trial

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: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BHV-3500 200mg<br>Zavegepant 200mg oral soft gel capsule. | Drug: BHV-3500 (zavegepant)<br>* BHV-3500 (zavegepant) softgel capsule.<br>|
| Placebo Comparator: Placebo 200mg<br>Matching placebo 200mg oral soft gel capsule. | Drug: Placebo<br>* Matching placebo softgel capsule.<br>|
| Active Comparator: BHV-3500 100mg<br>Zavegepant 100mg oral soft gel capsule. | Drug: BHV-3500 (zavegepant)<br>* BHV-3500 (zavegepant) softgel capsule.<br>|
| Placebo Comparator: Placebo 100mg<br>Matching placebo 100mg oral soft gel capsule. | Drug: Placebo<br>* Matching placebo softgel capsule.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of zavegepant compared to placebo as a preventive treatment for migraine | Measured by the mean reduction from baseline (i.e., Observation Phase) in the number of migraine days per month over the entire Double-blind Treatment Phase. | Number of migraine during weeks 1 to 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of zavegepant compared to placebo with the number of subjects that had a ≥ 50% reduction from Observational Phase. | Measured by the number of moderate to severe migraine days per month over the entire double-blind treatment phase. | Number of migraine days during weeks 1 to 12 | 
| Efficacy of zavegepant to placebo on mean reduction from Observational Phase. | Measured by the number of migraine days in the last 4 weeks of the Double-Blind Treatment Phase. | Number of migraine days during per month during weeks 9 to 12 | 
| Efficacy of zavegepant to placebo on mean reduction from Observational Phase. | Measured by the number of migraine days per month in the first 4 weeks of the Double-Blind Treatment Phase. | Number of migraine days per month during weeks 1 to 4 | 
| Efficacy of zavegepant to placebo in the mean number of acute migraine specific medication days per month. | Measured by the number of acute migraine specific medication days over the entire Double-Blind Treatment Phase. | Number of migraine days per month during weeks 1 to 12 | 
| Mean Change From Baseline in the Migraine Specific Quality of Life (MSQoL) Role Function-Restrictive Domain Score at Week 12 of the DBT Phase. | The change from baseline is calculated as the MSQoL restrictive role function domain score at Week 12 of the DBT phase minus the MSQoL restrictive role function domain score at baseline. | Week 12 of the double-blind treatment phase. | 
| Mean Change From Baseline in the Migraine Disability Assessment (MIDAS) Total Score at Week 12 of the DBT Phase. | The change from baseline is calculated as the MIDAS total score at Week 12 of the DBT phase minus the MIDAS total score at baseline. | Week 12 of the double-blind treatment phase. | 
| Evaluate the safety and tolerability of zavegepant. | This will be evaluated by the number of participants with treatment related adverse events by severity measured as mild, moderate, or severe. | From Baseline through Week 12 | 
| The frequency of ALT or AST elevations > 3x ULN, concurrently with bilirubin elevations > 2x ULN in subjects treated with zavegepent during the double-blind and open label phases. |  | From Baseline through Week 12 | 
| The frequency of hepatic related adverse events. | Measured by discontinuations in subjects treated with zavegepant due to elevated Liver Function Tests during the double-blind and open label phases | From Baseline through Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine Prevention, Phonophobia, Photophobia, Nausea