A Study to Assess the Adverse Events and Change in Disease Activity of Oral Atogepant Tablets in Pediatric Participants (6-17 Years of Age) With Episodic Migraine

Study Overview
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Brief Summary
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A migraine is a moderate to severe headache on one side of the head. A migraine attack is a headache that may be accompanied by throbbing, nausea, vomiting, sensitivity to light and sound, or other symptoms. A number of treatments are available for adults with migraine but there are limited approved treatments available for pediatric participants. The main goal of the study is to evaluate the safety and efficacy (how well treatment works) of a low-dose and high-dose of atogepant in pediatric participants between the ages of 6 and 17. Atogepant is a medicine currently approved to treat adults with episodic migraine (0 to 14 migraine days per month) and is being studied in pediatric participants between the ages of 6 and 17 with a history of episodic migraine. This is a Phase 3, randomized, double-blind study of atogepant in participants with a history of episodic migraine with an open-label pharmacokinetic substudy. Eligible participants will be randomized into 6 different groups. Participants between the ages of 12 and 17 will be randomized to receive placebo, low-dose atogepant, or high-dose atogepant for 12 weeks. Participants between the ages of 6 and 11 will also be randomized to receive placebo, low-dose atogepant, or high-dose atogepant for 12 weeks. The specific atogepant doses to be used in participants between the ages of 6 and 11 will be determined after the PK substudy is complete. Around 450 participants will be enrolled in approximately 100 sites. Placebo, low-dose atogepant, and high-dose atogepant are given as a tablet to take by mouth once a day. At the end of Week 12, participants will either undergo a follow-up visit 4 weeks after last study treatment or join an extension study where they can continue to receive atogepant for another 52 weeks. There may be a bigger responsibility for participants in this study. Participants will attend regular visits during the study at a hospital or clinic. The effects of 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, 12-Week, Double Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Atogepant for the Preventive Treatment of Episodic Migraine in Pediatric Subjects 6-17 Years of Age.

Conditions
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Episodic Migraine

Intervention / Treatment
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* Drug: Atogepant
* Drug: Placebo-Matching Atogepant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Weight is >= 20 kg (44 lbs) and < 135 kg (298 lbs). History of episodic migraine with or without aura consistent with a diagnosis according to the International Classification of Headache Disorders (ICHD) -3 (2018) for at least 6 months. Participant has to have 4 to 14 migraine days and < 15 headache days in the 28-day baseline period per eDiary. To be eligible for the PK substudy, participants must be 6 to 11 years of age (inclusive), with a history of migraine and per investigator judgment is appropriate to receive preventive treatment for migraine. Exclusion Criteria: History of migraine brainstem aura, hemiplegic migraine, or retinal migraine as defined by ICHD-3 (2018). Have a current diagnosis of chronic migraine as defined by ICHD-3 (2018). Have a current diagnosis of new persistent daily headache, trigeminal autonomic cephalgia (e.g., cluster headache), or painful cranial neuropathy as defined by ICHD-3 (2018). Have required in-hospital (excluding emergency department visits) treatment for migraine 3 or more times in the 6 months prior to Visit 1.

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 |
| --- | --- |
| Experimental: Open-Label PK Substudy: Atogepant Dose A (6-11 yrs)<br>Participants aged 6 to 11 will receive oral tablets of atogepant Dose A to determine appropriate dose for the 6-11 year old group in double-blind treatment period. | Drug: Atogepant<br>* Oral Tablet<br>* Other names: AGN-241689;|
| Experimental: Open-Label PK Substudy: Atogepant Dose B (6-11 yrs)<br>Participants aged 6 to 11 will receive oral tablets of atogepant Dose B to determine appropriate dose for the 6-11 year old group in double-blind treatment period. | Drug: Atogepant<br>* Oral Tablet<br>* Other names: AGN-241689;|
| Experimental: Double-Blind Treatment Period: High Dose Atogepant (12-17 yrs)<br>Participants aged 12 to 17 will receive oral tablets of high dose atogepant once a day for 12 weeks. | Drug: Atogepant<br>* Oral Tablet<br>* Other names: AGN-241689;|
| Experimental: Double-Blind Treatment Period: Placebo (12-17 yrs)<br>Participants aged 12 to 17 will receive oral tablets of placebo-matching atogepant once a day for 12 weeks. | Drug: Placebo-Matching Atogepant<br>* Oral Tablet<br>|
| Experimental: Double-Blind Treatment Period: Low Dose Atogepant (12-17 yrs)<br>Participants aged 12 to 17 will receive oral tablets of low dose atogepant once a day for 12 weeks. | Drug: Atogepant<br>* Oral Tablet<br>* Other names: AGN-241689;|
| Experimental: Double-Blind Treatment Period: High Dose Atogepant (6-11 yrs)<br>Participants aged 6-11 will receive oral tablets of high dose atogepant once a day for 12 weeks. | Drug: Atogepant<br>* Oral Tablet<br>* Other names: AGN-241689;|
| Experimental: Double-Blind Treatment Period: Placebo (6-11 yrs)<br>Participants aged 6 to 11 will receive oral tablets of placebo-matching atogepant once a day for 12 weeks. | Drug: Placebo-Matching Atogepant<br>* Oral Tablet<br>|
| Experimental: Double-Blind Treatment Period: Low Dose Atogepant (6-11 yrs)<br>Participants aged 6-11 will receive oral tablets of low dose atogepant once a day for 12 weeks. | Drug: Atogepant<br>* Oral Tablet<br>* Other names: AGN-241689;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Mean Monthly Migraine Days | A migraine day is defined as any calendar day on which a migraine occurs as per participant eDiary. Calendar days begin at midnight and last until 11:59 PM. | Baseline (Week 0) through Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Mean Monthly Headache Days | A headache day is defined as any calendar day on which headache pain lasting 2 hours or longer occurs unless an acute headache medication (e.g., ibuprofen, triptan) was used after the start of the headache, in which case no minimum duration will be specified. Calendar days begin at midnight and last until 11:59 PM. | Baseline (Week 0) through Week 12 | 
| Change from Baseline in Mean Monthly Acute Medication Use Days | An acute medication use day is defined as any day on which a participant reports, per eDiary, the intake of allowed medication(s) for the acute treatment of migraine. | Baseline (Week 0) through Week 12 | 
| Percentage of Participants who Achieve at least a 50% Reduction in Average of Monthly Migraine Days | A migraine day is defined as any calendar day on which a migraine occurs as per participant eDiary. Calendar days begin at midnight and last until 11:59 PM. | Baseline (Week 0) to 3 Months | 
| Change from Baseline in the Pediatric Quality of Life Inventory (PedsQL) total score | The PedsQL is a 23-item measure that evaluates quality of life in four areas of functioning: physical, emotional, social, and school functioning. The PedsQL yields a total quality of life score and two summary scores: Physical Health Summary Score and Psychosocial Health Summary Score. | Baseline (Week 0) through Week 12 | 
| Change from baseline in the Pediatric Migraine Disability Assessment (PedMIDAS) total score | The PedMIDAS scale evaluates the impact of headache on school performance, disability at home and social/sport function. The score is a composite of the total of 6 questions. | Baseline (Week 0) through Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Episodic Migraine, Atogepant, QULIPTA, AGN-241689