Evaluation of the Safety and Efficacy of Subcutaneous MEDI0618 in Reducing Migraine Headache Days in Adults with Episodic Migraine: A Randomized, Double-Blind Study

The primary objective of this Phase 2, randomized, multicenter, parallel-group, double-blind study is to assess the **efficacy** of repeat doses of **MEDI0618** in preventing migraine headaches in patients with episodic migraine. This objective is clinically relevant as it aims to determine the potential of MEDI0618 to reduce the frequency of migraine headache days, thereby improving the quality of life for individuals suffering from this condition. The study will compare the effects of MEDI0618 to a placebo to establish its therapeutic benefit.

The clinical trial involves a total of **555 participants** who are being studied to assess the efficacy of repeat doses of MEDI0618 in preventing migraine headaches in patients with **episodic migraine**. The study population includes both male and female subjects, aged between **18 to 70 years**, with a weight of at least 40 kg and a BMI of 18.0 kg/m² or higher. Participants have a history of migraine headaches, with or without aura, with the onset of migraines occurring at or before 50 years of age and persisting for at least 12 months prior to screening. They must have experienced at least 12 migraine headache days (MHDs) over the last 3 months before screening and meet specific criteria for migraine during a 4-week baseline data collection period. The trial includes individuals who can distinguish migraine headaches from tension-type headaches and have a history of unsuccessful treatment with at least three small molecule migraine preventive treatments from different classes. Female participants are required to be non-pregnant, not planning to become pregnant during the study, and must use adequate contraception if of childbearing potential. The trial population was selected based on these criteria to ensure a representative sample of individuals with episodic migraine, including those who may be considered vulnerable. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is a **Phase 2**, randomized, double-blind, controlled study designed to evaluate the safety and efficacy of **MEDI0618** in reducing migraine headache days in adult participants with episodic migraine. The trial will compare the effects of subcutaneous **MEDI0618** to a placebo. The study is expected to commence recruitment on November 1, 2024, and conclude by January 13, 2026. Participants will be involved in the study for a maximum treatment period of 12 weeks. The trial will include several key visits: an initial screening visit to assess eligibility based on criteria such as age, weight, and migraine history, followed by baseline data collection over four consecutive weeks. Participants will then be randomized to receive either **MEDI0618** or placebo via subcutaneous injection.

Throughout the study, participants will attend regular follow-up visits to monitor safety and efficacy outcomes, including the primary endpoint of change in the number of migraine headache days from baseline to the last four weeks of the treatment period. The end-of-study visit will occur after the 12-week treatment period, where final assessments will be conducted. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The trial aims to provide valuable insights into the potential of **MEDI0618** as a preventive treatment for migraine, with the primary objective being the reduction of migraine headache days in the target population.

The clinical trial involves the administration of **MEDI0618**, an experimental medication formulated as a **solution for injection**. This investigational product is developed by AstraZeneca AB and is classified as a biological substance with a protein origin. The active substance, also named MEDI0618, is administered via **subcutaneous injection**. The dosing regimen involves repeat doses over a maximum treatment period of 12 weeks. The specific dosage in milligrams and the frequency of administration are not detailed in the provided data. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in this double-blind study. The placebo is designed to match the MEDI0618 solution for injection in appearance but does not contain any active substance. The placebo administration follows the same route and schedule as the experimental medication to maintain the study's blinding integrity. The use of a placebo allows for the assessment of MEDI0618's efficacy in reducing migraine headache days in adult participants with episodic migraine, as compared to the placebo group.

The efficacy of the investigational product, **MEDI0618**, will be assessed in a Phase 2, randomized, multicenter, parallel-group, double-blind clinical trial. The primary endpoint for evaluating efficacy is the change in the number of migraine headache days (MHDs) from the 4-week baseline period to the last 4 weeks of the treatment period, specifically from Week 9 to Week 12. This endpoint will provide a quantitative measure of the reduction in migraine frequency, which is a critical indicator of the treatment's effectiveness in patients with episodic migraine.

Participants will be required to record their migraine headache days during the baseline period and throughout the treatment phase. The data collection will be conducted using validated patient-reported outcomes to ensure accuracy and reliability. The analysis will focus on comparing the change in MHDs between the group receiving MEDI0618 and the placebo group. This approach will help determine the therapeutic benefit of MEDI0618 in reducing the frequency of migraine headaches in the study population.