Randomized Study in Children and Adolescents With Migraine: Acute Treatment

Study Overview
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Brief Summary
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The purpose of this study is to test the safety and efficacy of BHV-3000 versus placebo in the acute treatment of moderate or severe migraine in children and adolescents.

Official Title
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Phase 3, Multicenter, Randomized, Double-blind, Group Sequential, Placebo-controlled Study to Assess Efficacy and Safety of Rimegepant for the Treatment of Migraine (With or Without Aura) in Children and Adolescents ≥ 6 to < 18 Years of Age

Conditions
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Pediatric Migraine

Intervention / Treatment
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* Drug: Rimegepant/BHV3000
* Drug: Matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of migraine (with or without aura) for > 6 months before Screening according to the IHS Classification ICHD-319 specifications for pediatric migraine. History may be verified using both medical records and recall by the participant and/or participant's parent(s)/legal representative(s). History of 1 to 8 moderate or severe attacks per month during the 2 months prior to enrollment, with attacks lasting > 3 hours without treatment, and attacks occurring at intervals > 24 hours. Prophylactic migraine medication are permitted if the dose has been stable for at least 12 weeks prior to the Baseline Visit, and the dose is not expected to change during the course of the study. Participants may remain on one (1) medication with possible migraine prophylactic effects, excluding CGRP antagonists [biologic or small molecule], during the treatment phases. Concomitant use of a CGRP antagonist, such as erenumab or fremanezumab, is prohibited. Previously discontinued prophylactic migraine medication must have done so at least 90 days prior to the Screening Visit. Verbally distinguish between migraine and other types of headaches. Participants must have a weight > 40 kg at the Screening Visit. Adequate venous access for blood sampling. Male and female participants ≥ 6 to < 18 years of age (participants must not reach their 18th birthday during the study). Exclusion Criteria: History of cluster headache or hemiplegic migraine headache. Confounding and clinically significant pain syndrome that may interfere with the participant's ability to participate in this study. Current psychiatric condition that is uncontrolled and/or untreated for a minimum of 6 months prior to the Screening Visit. Participants with a lifetime history of psychosis and/or mania. History of suicidal behavior or major psychiatric disorder. Current diagnosis or history of substance abuse; positive drug test at Screening. History of moderate or severe head trauma or other neurological disorder (including seizure disorder) or systemic medical disease that is likely to affect central nervous system functioning. Recent or planned surgery, requiring general anesthesia, <8 weeks prior to the Screening Visit. Participant has had gastrointestinal surgery that interferes with physiological absorption and motility (i.e., gastric bypass, duodenectomy, or gastric banding). Current diagnosis of viral hepatitis or a history of liver disease. Conditions considered clinically relevant in the context of the study such as uncontrolled hypertension (high blood pressure), diabetes, a life-threatening allergy

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 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: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BHV3000 (active drug)<br>BHV3000 (rimegepant) 75 mg or 50 mg ODT | Drug: Rimegepant/BHV3000<br>* BHV3000 (rimegepant) 75 mg or 50 mg ODT<br>|
| Placebo Comparator: Placebo<br>Matching 75 mg or 50 mg ODT placebo | Drug: Matching placebo<br>* Matching 75 mg or 50 mg ODT placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the efficacy of rimegepant compared with placebo in the acute treatment of migraine in adolescent population (≥ 12 to <18 years of age) as measured by pain freedom using the number of patients reporting no pain. | Pain freedom will be assessed in adolescent population (≥ 12 to < 18 years of age) on a 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe). | 2 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare rimegepant with placebo for pain freedom in children and adolescents combined. | Pain freedom will be assessed in children and adolescents (≥ 6 to < 18 years of age) using a 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe). Pain freedom will be assessed in children (> 6 to < 12 years of age) using the 5-Face VAS (Face 5 = 'severe pain', Faces 4 and 3 = 'moderate pain', Face 2 = 'mild pain', Face 1 = 'no pain'). | 2 hours post-dose | 
| To compare rimegepant with placebo on freedom from the most bothersome symptom (MBS) associated with migraine in adolescents. | Freedom from MBS (nausea, phonophobia or photophobia) will be measured using a binary scale (0=absent, 1=present). | 2 hours post-dose | 
| To compare rimegepant with placebo on the probabilities of requiring rescue medication within in adolescents. | Use of rescue medication will be assessed using the numbers of participants that take rescue medication. | Within 24 hours and 48 hours of initial treatment | 
| To compare rimegepant with placebo on sustained pain freedom in adolescents. | Sustained pain freedom will be assessed using the number of participants that do not use any rescue medications and do not experience any headache pain post dose. | 2 to 24 hours post-dose | 
| To compare rimegepant with placebo on sustained pain freedom in adolescents. | Sustained pain freedom will be assessed using the number of participants that do not use any rescue medications and do not experience any headache pain post dose. | 2 to 48 hours post-dose | 
| To compare rimegepant with placebo on the ability to function normally as reported on the Functional Disability scale in adolescents. | The proportion of participants able to function normally will be assessed using the number that self-report as normal on the Functional Disability scale. | 2 hours post-dose | 
| To compare rimegepant with placebo for pain freedom in children. | Pain freedom will be assessed using the number of children (≥ 6 to < 12 years of age) that report no pain measured by a 5-Face VAS (Face 5 = 'severe pain', Faces 4 and 3 = 'moderate pain', Face 2 = 'mild pain', Face 1 = 'no pain'). | 2 hours post-dose | 
| To compare rimegepant with placebo on freedom from the most bothersome symptom (MBS) associated with migraine in children and combined children and adolescents. | Freedom from the most bothersome symptom (nausea, phonophobia or photophobia) will be assessed using the number of participants that report the absence of MBS measured using a binary scale (0=absent, 1=present). | 2 hours post-dose | 
| To compare rimegepant with placebo on the probabilities of requiring rescue medication in children and combined children and adolescents. | The probabilities of requiring rescue medication will be assessed using the numbers of participants that take rescue medication within initial treatment. | Within 24 hours and 48 hours of initial treatment. | 
| To compare rimegepant with placebo on sustained pain freedom in children and combined children and adolescents. | Sustained pain freedom will be assessed using the number of participants that do not use any rescue medications and do not experience any headache pain post dose. | 2 to 24 hours post-dose | 
| To compare rimegepant with placebo on sustained pain freedom in children and combined children and adolescents. | Sustained pain freedom will be assessed using the number of participants that do not use any rescue medications and do not experience any headache pain post dose. | 2 to 48 hours post-dose | 
| To compare rimegepant with placebo on freedom from photophobia in adolescents, children and combined children and adolescents. | Freedom from photophobia will be assessed by the number of participants that report the absence of photophobia post dose that reported the presence of photophobia at baseline. | 2 hours post-dose | 
| To compare rimegepant with placebo on freedom from phonophobia in adolescents, children and combined children and adolescents. | Freedom from phonophobia will be assessed by the number of participants that report the absence of phonophobia post dose that reported the presence of phonophobia at baseline. | 2 hours post-dose | 
| To compare rimegepant with placebo on freedom from nausea in adolescents, children and combined children and adolescents. | Freedom from nausea will be assessed by the number of participants that report the absence of nausea post dose that reported the presence of nausea at baseline. | 2 hours post-dose | 
| To compare rimegepant with placebo on pain relief in adolescents, children and combined children and adolescents. | Pain relief will be assessed using the number of participants that report a pain level of moderate or severe at baseline and then report a pain level of none or mild post dose. | 2 hours post-dose | 
| To compare rimegepant with placebo in adolescents, children and combined children and adolescents on pain relief. | Time to first report of pain relief will be based on the first time point a participant reports a pain level of none or mild. | Time to patients first report of pain relief of none or mild post dose up to 48 hours. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine, Acute treatment, Phonophobia, Photophobia, Nausea, Pediatric, Children, Adolescent, Pediatric Migraine