Efficacy and Safety Evaluation of Eptinezumab for Preventive Treatment in Adults with Chronic Migraine: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy** of eptinezumab in the prevention of **chronic migraine** in participants. Chronic migraine is a debilitating condition characterized by frequent headache attacks, significantly impacting the quality of life. The clinical relevance of this objective lies in the potential of eptinezumab to reduce the frequency and severity of migraine episodes, thereby improving patient outcomes and reducing the burden of the disease.

The clinical trial involves a total of **615 participants** diagnosed with **chronic migraine**. The study population includes both male and female subjects, aged between 18 and 75 years, with a history of migraine onset at least 12 months prior to the screening visit. Participants were selected based on their compliance with specific criteria, including having at least 8 migraine days per month for each of the 3 months preceding the screening visit and demonstrating adherence to the Headache eDiary. The trial does not exclude vulnerable populations, and participants are required to have a general health status that allows for the evaluation of the efficacy of eptinezumab in preventing migraines. Lifestyle factors such as diet and physical activity were not specified as part of the selection criteria.

The clinical trial is designed as an **interventional, randomized, double-blind, parallel-group, placebo-controlled** study to evaluate the efficacy and safety of **eptinezumab** for the preventive treatment of **chronic migraine**. The trial aims to assess the ability of eptinezumab to reduce the number of monthly migraine days (MMDs) in participants diagnosed with chronic migraine. The study is expected to run until July 31, 2025, with recruitment having commenced on May 29, 2021. Participants will be involved in the study for a maximum treatment period of 24 weeks.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit where eligibility is confirmed based on criteria such as a history of migraine onset at least 12 months prior, and experiencing at least 8 migraine days per month in the 3 months preceding the screening. Compliance with a headache eDiary is also required, with data entry for at least 24 of the 28 days following the screening visit. The primary endpoint is the change from baseline in the number of MMDs, evaluated from weeks 1 to 12. Secondary endpoints include a ≥50% reduction in MMDs from baseline during weeks 1 to 12, a ≥75% reduction in MMDs from baseline during weeks 1 to 4 and weeks 1 to 12, and the migraine rate on the day after dosing.

Study visits will include follow-up assessments to monitor the efficacy and safety of the treatment. The end-of-study visit will conclude the participant's involvement, assessing the overall outcomes and any adverse events. Participants may be terminated early from the study if they do not comply with the study protocol, experience significant adverse effects, or withdraw consent. The trial is conducted under strict adherence to ethical guidelines and regulatory requirements 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 protein-based biological agent classified under the ATC code **N02CX**, which pertains to other antimigraine preparations. The pharmaceutical form of VYEPTI is a concentrate for solution for infusion, and it is administered via the **intravenous route**. The maximum daily dose is 300 mg, with a total maximum dose of 600 mg over the course of the treatment. The treatment period is set for a maximum of 24 weeks. The product is not a pediatric formulation and is not classified as an orphan drug. The manufacturer of VYEPTI is H. Lundbeck A/S.

In this randomized, double-blind, parallel-group, placebo-controlled study, a placebo is used as the comparator treatment. The placebo is administered in the same manner as the experimental medication, ensuring that the study remains blinded and the efficacy of eptinezumab can be accurately assessed. The placebo is designed to mimic the appearance and administration route of VYEPTI, maintaining the integrity of the study design.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. This includes regular assessments and documentation of infusion administration, as well as monitoring for any adverse events or deviations from the prescribed dosing regimen. The study aims to evaluate the efficacy and safety of eptinezumab in the preventive treatment of **migraine** in participants with chronic migraine.

The efficacy of eptinezumab in the preventive treatment of **migraine** will be assessed through a series of primary and secondary endpoints. The primary endpoint is the change from baseline in the number of monthly migraine days (MMDs), evaluated over the course of Weeks 1 to 12. Secondary endpoints include the proportion of participants achieving a ≥50% reduction from baseline in MMDs during Weeks 1 to 12, a ≥75% reduction from baseline in MMDs during Weeks 1 to 4, and a ≥75% reduction from baseline in MMDs during Weeks 1 to 12. Additionally, the migraine rate on the day after dosing (Day 1) will be assessed.

Data collection will involve the use of an electronic diary (eDiary) where participants will record migraine occurrences and headache days. Compliance with the eDiary is required, with participants expected to enter data for at least 24 of the 28 days following the Screening Visit. The efficacy parameters will be measured and analyzed at specified timepoints, including Weeks 1 to 4 and Weeks 1 to 12, to determine the impact of eptinezumab on migraine prevention. The study is designed as an interventional, randomized, double-blind, parallel-group, placebo-controlled trial, ensuring rigorous evaluation of the treatment's efficacy.