Efficacy and Safety Evaluation of Intravenous Eptinezumab for Preventive Treatment of Chronic Migraine in Adolescents: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this study is to evaluate the **efficacy** of intravenous **eptinezumab** compared to placebo in reducing the number of migraine days in adolescents aged 12 to 17 years with chronic migraine. This is clinically relevant as chronic migraine significantly impacts the quality of life and daily functioning in this age group, and effective preventive treatments are essential for managing this condition.

The clinical trial involves a total of **165 participants** who are young individuals aged **12 to 17 years** diagnosed with **chronic migraine**. The study population includes both **male and female** subjects, and it is noted that a vulnerable population is selected. Participants were chosen based on specific criteria, including a documented history of migraine, with or without aura, as per the International Classification of Headache Disorders 3 (ICHD-3) guidelines. During a 28-day screening period, participants were required to complete a headache eDiary on at least 23 days, with a record of 15 to 26 headache days, including at least 8 migraine days. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection process ensures that the participants meet the necessary health status and documentation requirements to assess the efficacy of eptinezumab compared to a placebo in reducing migraine days.

The clinical trial is designed as an **interventional, randomized, double-blind, parallel-group, placebo-controlled** study to evaluate the efficacy and safety of intravenous **eptinezumab** in adolescents aged 12 to 17 years for the preventive treatment of chronic **migraine**. The trial aims to determine if eptinezumab is more effective than a placebo in reducing the number of migraine days in this population. The study is expected to run from November 2022 to March 2026, with participant involvement lasting up to 12 months.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a diagnosis of migraine according to the International Classification of Headache Disorders 3 guidelines and a history of chronic migraine for at least six months. During the 28-day screening period, participants must complete a headache eDiary on at least 23 of the 28 days and report 15 to 26 headache days, with at least 8 being migraine days.

Following successful screening, participants will be randomized to receive either eptinezumab or a placebo (normal saline solution) via intravenous infusion. The primary endpoint is the change from baseline in monthly migraine days averaged over weeks 1 to 12. Secondary endpoints include the percentage of participants with a 50% or 75% reduction in monthly migraine days, changes in the use of acute medication, and the presence of specific anti-eptinezumab antibodies.

Study visits will include regular follow-up assessments to monitor efficacy and safety, with the final visit marking the end of the study. Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or choose to withdraw consent. The trial is conducted under strict regulatory guidelines to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **VYEPTI**, a **100 mg concentrate for solution for infusion**. The active substance in VYEPTI is **eptinezumab**, a monoclonal antibody classified under the ATC code **N02CX**, which pertains to other antimigraine preparations. Eptinezumab is derived from a protein of other origin and is intended for **intravenous use**. The maximum daily and total dose of eptinezumab is 300 mg, administered over a treatment period of up to 12 weeks. The product has been repackaged for blinding purposes to maintain the integrity of the double-blind study design. The pharmaceutical form is a concentrate that requires preparation into a solution for infusion prior to administration.

The comparator treatment in this study is a **placebo**, specifically **Nacl 0.9%**. This placebo is used to mimic the administration of the experimental treatment without providing any active therapeutic effect. The placebo is administered in a manner consistent with the experimental treatment to ensure blinding and maintain the study's integrity. The use of a placebo allows for the evaluation of the efficacy and safety of eptinezumab in reducing the number of migraine days in adolescents aged 12 to 17 with chronic migraine.

Efficacy in this clinical trial will be assessed by evaluating the change from baseline in monthly migraine days (MMDs) averaged over weeks 1 to 12. This primary endpoint will provide a quantitative measure of the reduction in migraine frequency, which is a critical indicator of the treatment's effectiveness. Secondary endpoints will include the percentage of participants achieving a 50% and 75% reduction from baseline in MMDs over specified timeframes, such as weeks 1 to 12 and weeks 1 to 4. Additionally, the trial will assess changes from baseline in monthly headache days, the rate of migraines with severe pain intensity, and days with the use of acute medication, all averaged over weeks 1 to 12.

Further efficacy assessments will involve the Pediatric Migraine Disability Assessment Questionnaire (PedMIDAS) score, which will be averaged over weeks 1 to 12 to evaluate the impact of treatment on migraine-related disability. The trial will also monitor free **eptinezumab** plasma concentration and the presence of specific anti-eptinezumab antibodies, including those with neutralizing activity, to understand the pharmacokinetic and immunogenic profile of the treatment. These parameters will be collected and analyzed at predetermined intervals throughout the study to ensure a comprehensive evaluation of the treatment's efficacy in the adolescent population with chronic migraine.