Evaluation of Rimegepant for Migraine Prophylaxis in Pediatric Patients Aged 6 to <18 Years: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this study is to evaluate the **efficacy** of rimegepant compared to placebo as a preventive treatment for **migraine** in adolescents aged 12 to less than 18 years with episodic migraine. This is measured by the mean reduction from the observation period in the number of migraine days per month over the entire course of the double-blind treatment phase. This objective is clinically relevant as it aims to establish the potential of rimegepant in reducing the frequency of migraine episodes, which can significantly impact the quality of life and daily functioning of adolescents.

Secondary objectives include:

• Comparing the efficacy of rimegepant to placebo on the proportion of participants achieving at least a 50% reduction in the number of moderate to severe migraine days per month over the entire double-blind treatment phase.
• Assessing the mean reduction from the observation period in the number of moderate to severe headache days per month over the entire double-blind treatment phase.
• Evaluating the mean reduction from the observation period in the number of migraine days per month during the first 4 weeks of the double-blind treatment phase.
• Comparing the change from baseline in the Pediatric Quality of Life (PedsQL™) 4.0 Generic Core Scales total score at Week 12 of the double-blind treatment phase between rimegepant and placebo.

These secondary objectives are crucial for understanding the broader impact of rimegepant on migraine-related symptoms and overall quality of life in the adolescent population.

The clinical trial involves a total of **659 participants** who are adolescents aged **12 to <18 years**. The study population includes both **male and female** subjects, with a focus on individuals diagnosed with **migraine (with or without aura)**. Participants were selected based on specific criteria, including a history of migraine consistent with the International Classification of Headache Disorders, 3rd Edition. The trial population is characterized by having 14 or fewer headache days per month and at least 6 migraine days during the observation period. Participants are required to have a Pediatric Migraine Disability Assessment Scale (PedMIDAS) Disability Score between >10 and ≤50 at baseline. The study allows for the inclusion of individuals on stable prophylactic migraine medication. Participants must weigh more than 15 kg, with a specific requirement of over 25 kg for those in EU countries. The trial includes a vulnerable population, and all participants must have no clinically significant abnormalities in medical or laboratory evaluations. The study ensures that female participants of childbearing potential use effective contraception throughout the trial. The selection process required signed informed consent or assent according to local regulations.

The clinical trial is a **Phase 3**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of **rimegepant** in the prevention of **migraine** in children and adolescents aged 6 to less than 18 years. The trial aims to compare the efficacy of rimegepant to placebo by measuring the mean reduction in the number of migraine days per month over the entire double-blind treatment phase, which spans 12 weeks. The study is expected to conclude by June 2027, with recruitment having commenced in December 2022.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as a history of migraine consistent with the International Classification of Headache Disorders, a Pediatric Migraine Disability Assessment Scale score, and stable prophylactic migraine medication use if applicable. Following the screening, eligible participants will enter the observation period, during which baseline data will be collected. The randomization (baseline) visit will mark the start of the double-blind treatment phase, where participants will be randomly assigned to receive either rimegepant or placebo.

Throughout the trial, participants will attend follow-up visits to monitor safety and efficacy outcomes, including the primary endpoint of mean change in migraine days and secondary endpoints such as the percentage of participants with a ≥50% reduction in moderate to severe migraine days. The end-of-study visit will occur after the completion of the 12-week treatment phase, where final assessments will be conducted.

Participant involvement is expected to last approximately 64 weeks, including the observation and treatment phases. Conditions that may lead to early termination from the study include significant protocol deviations, adverse events, or withdrawal of consent. The trial is conducted under strict adherence to ethical guidelines, ensuring the safety and well-being of all participants.

The clinical trial involves the administration of **Rimegepant** in two different formulations, as well as a placebo. The first experimental medication is a 25 mg oral lyophilisate of Rimegepant, produced by Pfizer Inc. This formulation is administered orally and is of chemical origin. The maximum daily dose is 75 mg, with a total treatment period of up to 64 days. The active substance, Rimegepant, is a chemical compound also known by synonyms such as BMS927711 and BHV-3000. The dosing schedule involves oral administration, and participant compliance is monitored throughout the trial.

The second experimental medication is VYDURA, a 75 mg oral lyophilisate of Rimegepant, manufactured by Pfizer Europe MA EEIG. Similar to the 25 mg formulation, this medication is also administered orally and is chemically derived. The maximum daily and total dose is 75 mg, with a treatment duration of up to 64 days. The active substance remains Rimegepant, with the same chemical synonyms. The administration route is oral, and adherence to the dosing schedule is closely monitored to ensure participant compliance.

The study also includes a **placebo** group, utilizing a Rimegepant placebo. The placebo is designed to mimic the appearance and administration route of the active medications, ensuring the study remains double-blind. The placebo is administered orally, and participant compliance is similarly monitored to maintain the integrity of the trial results. The use of a placebo allows for a controlled comparison to evaluate the efficacy and safety of Rimegepant in the prevention of migraine in the study population.

The efficacy of **rimegepant** in the prevention of migraine in adolescents will be assessed through a series of primary and secondary endpoints. The primary endpoint is the mean change from baseline in the number of migraine days per month over the entire double-blind treatment (DBT) phase, which spans Weeks 1 to 12. This will be measured in adolescents with episodic migraine. Secondary endpoints include the percentage of participants achieving a ≥50% reduction from the observation period in the number of moderate to severe migraine days per month over the DBT phase, the mean change from the observation period in the number of moderate to severe headache days per month, and the mean change in the number of migraine days per month during the first 4 weeks of the DBT phase. Additionally, the mean change from baseline in the Pediatric Quality of Life (PedsQLTM) total score at Week 12 will be evaluated.