Study of BOTOX Injections in Prevention of Migraine in Adult Participants With Episodic Migraine

Study Overview
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Brief Summary
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Migraine is a neurological disease characterized by moderate or severe headache, associated with nausea, vomiting, and/or sensitivity to light and sound (ICHD 2018). Migraine can be further categorized according to the frequency of attacks as episodic migraine (EM) or chronic migraine (CM). This study will assess the effects of BOTOX in preventing migraine in adult participants with EM. BOTOX is being developed for the prevention of migraine in adults with episodic migraine (EM). Participants will be enrolled in 3 different treatment groups. There is 1 in 3 chance that participants will be assigned to receive placebo. Approximately 777 adult participants with EM will be enrolled in approximately 125 sites across the world. Participants will receive intramuscular injections (injected into the muscle) of BOTOX or Placebo on Week 0 and Week 12. Eligible participants will receive BOTOX on Week 24 and Week 36. 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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Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Study of BOTOX (Botulinum Toxin Type A) for the Prevention of Migraine in Subjects With Episodic Migraine

Conditions
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Episodic Migraine

Intervention / Treatment
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* Drug: BOTOX
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of migraine headache disorder meeting International Classification of Headache Disorders (ICHD)-3 diagnostic criteria for migraine with aura or migraine without aura for >= 12 months. Onset of migraine before 50 years of age. History of 6 to 14 migraine days/month in each of the 3 months prior to Visit 1. Six to 14 migraine/probable migraine days during the 4-week screening/baseline phase. Less than 15 headache days/month in each of the 3 months prior to Visit 1 and during the 4-week screening/baseline phase. Exclusion Criteria: Current diagnosis of chronic migraine according to ICHD-3. History or current diagnosis of migraine with brainstem aura, retinal migraine, complications of migraine, tension-type headache, trigeminal autonomic cephalalgias, hypnic headache, hemicrania continua, or new daily persistent headache. History of headache attributed to another disorder (eg, secondary headaches), except medication overuse headache. History of an inadequate response to >4 medications (2 of which have different mechanisms of action) prescribed for the prevention of migraine. Pregnant or nursing females.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BOTOX Dose A<br>Participants will receive BOTOX Dose A on Week 0 and Week 12. Eligible participants will receive BOTOX Dose A on Week 24 and Week 36. | Drug: BOTOX<br>* Intramuscular Injection<br>* Other names: Botulinum Toxin Type A;|
| Experimental: BOTOX Dose B<br>Participants will receive BOTOX Dose B on Week 0 and Week 12. Eligible participants will receive BOTOX Dose A on Week 24 and Week 36. | Drug: BOTOX<br>* Intramuscular Injection<br>* Other names: Botulinum Toxin Type A;|
| Placebo Comparator: Placebo<br>Participants will receive placebo on Week 0 and Week 12. Eligible participants will receive BOTOX Dose A on Week 24 and Week 36. | Drug: BOTOX<br>* Intramuscular Injection<br>* Other names: Botulinum Toxin Type A;Drug: Placebo<br>* Intramuscular Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Frequency of Monthly Migraine Days | Change from baseline in the frequency of monthly migraine days (i.e., migraine or probable migraine headache days) will be assessed. | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Frequency of Monthly Headache Days | Change from baseline in the frequency of monthly headache days will be assessed. | 6 Months | 
| Responder Status of 50% Reduction From Baseline in the Frequency of Monthly Migraine Days | Percentage of participants achieving 50% reduction from baseline in the frequency of monthly migraine days will be assessed. | 6 Months | 
| Change From Baseline in the Frequency of Monthly Acute Headache Medication Days | The change from baseline in acute migraine medication use days will be assessed. | 6 Months | 
| Change From Baseline in Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ v2.1) Role Function - Restrictive (RFR) Domain Score | Role Function Restrictive (RFR) domain assesses how migraines limit one's daily social and work-related activities using a 6-point scale ranging from none of the time to all of the time. | 6 Months | 
| Change From Baseline in the Activity Impairment in Migraine - Diary (AIM-D) Physical Impairment Domain Score | AIM-D Physical impairment Domain Score asks participants to rate the level of difficulty experienced with physical impairment using a 6-point rating scale ranging from not difficult at all to I could not do it at all. | 6 Months | 
| Change From Baseline in the Frequency of Monthly Neck Pain Days Associated With Headache Among Participants Who Report at least 1 day of Neck Pain Associated With Headache During Baseline | Change from baseline in the frequency of monthly neck pain days associated with headache will be assessed among participants who report at least 1 day of neck pain associated with headache during baseline. | 6 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine, Episodic Migraine, BOTOX, Botulinum Toxin Type A)