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 to 17 years of age

The primary objective of this Phase 3, multicenter, double-blind, placebo-controlled study is to evaluate the **safety** and **efficacy** of two doses of **atogepant** (low and high) administered daily for the preventive treatment of **episodic migraine** in pediatric participants aged 6 to 17 years. This objective is clinically relevant as it aims to establish a therapeutic option for managing episodic migraine in a pediatric population, potentially reducing the frequency and severity of migraine episodes, thereby improving the quality of life for affected individuals.

The secondary efficacy objective is to demonstrate improvement in efficacy for treatment with atogepant compared to placebo concerning the secondary endpoints. This evaluation will provide additional insights into the therapeutic benefits of atogepant beyond the primary endpoints, further supporting its use in clinical practice for pediatric patients with episodic migraine.

The clinical trial involves a total of **277 participants** diagnosed with **episodic migraine**. The study population comprises pediatric subjects aged 6 to 17 years, including both male and female participants. The selection criteria for the trial population required individuals to have a history of episodic migraine, with or without aura, consistent with the International Classification of Headache Disorders (ICHD) -3 (2018) for at least six months. Participants were required to have between 4 to 14 migraine days and fewer than 15 headache days in the last 28-day baseline period, as recorded in an electronic diary. The trial includes a vulnerable population, and participants' weight must be between 20 kg (44 lbs) and 135 kg (298 lbs). The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial aims to evaluate the safety and efficacy of two doses of atogepant, administered daily, for the treatment of episodic migraine in this pediatric cohort.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the safety and efficacy of **atogepant** for the preventive treatment of **episodic migraine** in pediatric subjects aged 6 to 17 years. The trial will span a duration of 12 weeks, with participants receiving either a low or high dose of atogepant or a placebo. The primary objective is to assess the change from baseline in mean monthly migraine days across the treatment period. Secondary endpoints include changes in mean monthly headache days, acute medication use days, and quality of life scores as measured by the PedsQL and PedMIDAS at Week 12.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as weight and migraine history. Following randomization, participants will attend regular follow-up visits to monitor safety and efficacy outcomes. The end-of-study visit will conclude the trial, where final assessments will be conducted. The expected length of participant involvement is approximately 12 weeks, with conditions for early termination including non-compliance with the study protocol or adverse events that compromise participant safety.

Inclusion criteria require participants to have a history of episodic migraine consistent with the International Classification of Headache Disorders (ICHD) -3, with 4 to 14 migraine days in the last 28-day baseline period. Participants must weigh between 20 kg and 135 kg. The trial will exclude individuals who do not meet these criteria or who have conditions that may interfere with the study outcomes. The trial is set to commence recruitment on August 15, 2023, with an estimated end date of May 3, 2028.

The clinical trial involves the administration of **Atogepant**, a chemical compound developed by Allergan Sales, LLC, a subsidiary of AbbVie Inc. Atogepant is provided in the form of a **tablet** and is intended for oral administration. The trial evaluates two dosages of Atogepant, with a maximum daily dose of 60 mg and a total maximum dose of 5040 mg over a 12-week period. The primary objective is to assess the safety and efficacy of Atogepant for the preventive treatment of episodic migraine in pediatric subjects aged 6 to 17 years. The pharmaceutical form of Atogepant is consistent across the trial, ensuring uniformity in administration and dosage.

In addition to the experimental medication, the study includes a **placebo** control group. The placebo is designed to match the Atogepant tablets in appearance but contains no active substance. Two variations of the placebo are used, corresponding to the 10 mg and 60 mg Atogepant tablets. The placebo is administered in a similar manner to the active drug, ensuring blinding and maintaining the integrity of the double-blind study design. The use of a placebo allows for a controlled comparison to evaluate the true efficacy of Atogepant in the treatment of episodic migraine.

The efficacy of **Atogepant** in the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the change from baseline in mean monthly migraine days across the 12-week treatment period. This will provide a direct measure of the drug's effectiveness in reducing the frequency of migraine episodes in pediatric subjects aged 6 to 17 years.

Secondary endpoints include several additional measures to further evaluate efficacy. These are: the change from baseline in mean monthly headache days, the change from baseline in mean monthly acute medication use days, and the achievement of at least a 50% reduction in the 3-month average of monthly migraine days. Additionally, changes from baseline in the Pediatric Quality of Life Inventory (PedsQL) total score and the Pediatric Migraine Disability Assessment (PedMIDAS) total score at Week 12 will be assessed. These endpoints will help to determine the broader impact of the treatment on the quality of life and functional impairment associated with episodic migraine.

The efficacy parameters will be collected and analyzed at specified timepoints throughout the trial, including baseline and Week 12. The use of validated scales such as the PedsQL and PedMIDAS ensures that the assessments are reliable and standardized. The trial is designed as a double-blind, placebo-controlled study, which will help to ensure the objectivity and validity of the efficacy assessments.