Efficacy of Eptinezumab as Adjunctive Therapy in Preventing Migraine and Treating Medication Overuse Headache in Patients with Dual Diagnosis

The primary objective of this study is to evaluate the **efficacy** of Eptinezumab as an add-on treatment to brief education intervention for the prevention of **migraine** and the treatment of **Medication Overuse Headache** (MOH) in patients with a dual diagnosis of these conditions. This is clinically relevant as it addresses the need for effective preventive strategies in patients suffering from chronic migraine and MOH, which are often challenging to manage due to the complexity of their co-occurrence and the potential for medication overuse to exacerbate headache frequency and severity.

The clinical trial involves a total of **95 participants** diagnosed with **chronic migraine**, **migraine**, or **medication overuse headache**. The study population includes both male and female subjects, aged between 18 and 75 years, who have been confirmed to meet the diagnostic criteria as per the IHS ICHD-3 guidelines. Participants were selected based on their history of migraine onset at or before 50 years of age and a history of treatment failure with at least one preventive treatment within the last five years. The trial includes individuals who have demonstrated compliance with a headache eDiary, recording data for at least 24 out of 28 days following the screening visit. The study population is characterized by regular overuse of medications for acute headache treatment for more than three months prior to the screening. Participants have experienced at least 8 migraine days per month and 15 headache days per month over the three months preceding the screening. The trial does not exclude vulnerable populations, ensuring a comprehensive evaluation of the efficacy of Eptinezumab as an add-on to BI for migraine prevention and MOH treatment.

The clinical trial is designed as an **interventional**, **randomized**, **double-blind**, parallel-group, placebo-controlled study to evaluate the efficacy of **eptinezumab** as an add-on treatment for the preventive management of **migraine** and **medication overuse headache** (MOH). The trial aims to assess the change from baseline in the number of monthly headache days (MHDs) and monthly migraine days (MMDs) over specified periods. The study is expected to run from April 2022 to March 2025, with participant involvement lasting up to 72 weeks.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as a diagnosis of chronic migraine (CM) and MOH according to IHS ICHD-3 guidelines, a history of treatment failure with at least one preventive treatment, and compliance with headache eDiary entries. Following the screening, eligible participants will be randomized to receive either eptinezumab or placebo via **intravenous use**. The primary endpoint will be evaluated by the change in MHDs from baseline during weeks 1-4, with secondary endpoints including changes in MMDs and daily pain assessment scores over longer periods.

Participants will attend follow-up visits at regular intervals to monitor efficacy and safety outcomes, with data collected on headache frequency, medication use, and adverse events. The end-of-study visit will conclude the trial, assessing the long-term impact of the treatment. Conditions for early termination from the study include non-compliance with study procedures, withdrawal of consent, or adverse events that compromise participant safety. The trial is not categorized as low intervention and is conducted in a Phase IV setting to further understand the therapeutic benefits of eptinezumab in this patient population.

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 of biological origin, specifically classified under the ATC code N02CX, which denotes other antimigraine preparations. The pharmaceutical form of VYEPTI is a concentrate that requires dilution prior to administration. The medication is administered via **intravenous use**. The maximum daily and total dose is 300 mg, with a treatment period extending up to 72 weeks. The administration schedule is designed to ensure optimal efficacy in the preventive treatment of migraine and Medication Overuse Headache (MOH).

In this randomized, double-blind, parallel-group, placebo-controlled study, the experimental treatment with eptinezumab is compared against a placebo. The placebo is designed to mimic the experimental treatment in appearance and administration route, ensuring the blinding of participants and investigators. The placebo is administered intravenously at the same frequency as the experimental drug, maintaining consistency in the treatment protocol. Compliance with the dosing schedule is monitored through regular assessments and documentation to ensure adherence to the study protocol.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the change from baseline in the number of monthly headache days (MHDs) during weeks 1 to 4. Secondary endpoints include changes from baseline in monthly migraine days (MMDs) and MHDs over weeks 1 to 12, as well as the fulfillment of the International Classification of Headache Disorders, 3rd edition (ICHD-3) diagnostic criteria for chronic migraine (CM) and **Medication Overuse Headache (MOH)** at weeks 4 and 12. Additional secondary endpoints involve changes from baseline in average daily pain assessment scores during weeks 1 to 2, and changes in monthly days with acute medication use over weeks 1 to 4 and weeks 1 to 12.

Data collection will occur at specified intervals throughout the trial, with efficacy parameters being measured at baseline and at designated time points such as weeks 4 and 12. The trial will utilize validated scales and patient-reported outcomes to ensure accurate and reliable data collection. The analysis will focus on comparing the changes from baseline in the specified endpoints to evaluate the efficacy of eptinezumab as an add-on treatment for the prevention of migraine and treatment of MOH.