Phase II Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of IPN10200 for Episodic and Chronic Migraine Prevention in Adults

The primary objective of this study is to assess the **safety** and **tolerability** of a single treatment cycle of IPN10200 in adult participants with episodic migraine (EM) or chronic migraine (CM). Additionally, the study aims to evaluate the potential **immunogenicity** of IPN10200. Clinically, understanding the safety profile and potential immune response is crucial for determining the viability of IPN10200 as a preventive treatment for migraine, ensuring that it does not pose undue risk to patients.

Secondary objectives include:

• Comparing the magnitude of change in the frequency of monthly migraine days (MMDs) and monthly headache days (MHDs) following a single treatment cycle of IPN10200 or placebo.
• Evaluating the improvement in migraine and headache prevention response.
• Assessing changes in the frequency of moderate/severe headache days.
• Determining if IPN10200 is superior to placebo in the prevention of migraine, as assessed by changes in the frequency of migraine and headache days, and the use of acute medication.
• Assessing the safety and tolerability of IPN10200 in the CM and EM groups independently.
• Evaluating the potential immunogenicity of IPN10200 in these groups.

These secondary objectives are clinically relevant as they provide insights into the efficacy of IPN10200 in reducing migraine and headache frequency, improving patient outcomes, and potentially reducing the need for acute medication. This information is vital for establishing IPN10200 as a viable preventive treatment option for migraine sufferers.

The clinical trial involves a total of **387 participants** diagnosed with either **episodic migraine** or **chronic migraine**. The study population includes both male and female adults aged between 18 and 80 years. Participants were selected based on their ability to provide informed consent and a confirmed diagnosis of migraine according to ICHD-3 criteria for at least 12 months prior to the screening visit. The trial includes individuals with a history of using at least one preventive treatment for migraine. Participants in the episodic migraine group have a history of up to 14 headache days and at least 6 migraine days in the 4 weeks prior to randomization, while those in the chronic migraine group have a history of at least 15 headache days and 8 migraine days in the same period. The trial population is not limited by gender, and both male and female subjects are included. The study also considers vulnerable populations, ensuring a comprehensive assessment of the investigational product's safety and efficacy across diverse demographic groups.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the safety and efficacy of IPN10200 in the prevention of **episodic migraine** and **chronic migraine** in adults. The trial is structured in a dose escalation and dose-finding phase II format, with the primary objective of assessing the safety, tolerability, and potential immunogenicity of a single treatment cycle of IPN10200. The study aims to determine if IPN10200 is superior to placebo in preventing migraines when administered as a single treatment cycle. The trial is expected to commence recruitment on August 15, 2025, and conclude by June 15, 2027, with an overall duration of approximately 22 months.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of migraine per ICHD-3 criteria, and history of preventive treatment use. Following randomization, participants will receive either IPN10200 or placebo via **intramuscular** injection. The study includes multiple follow-up visits to monitor safety and efficacy, with assessments at baseline, Week 4, Week 12, and Week 36. These visits will evaluate primary endpoints such as the percentage of participants experiencing adverse events, changes in laboratory parameters, vital signs, and the presence of binding and neutralizing antibodies to IPN10200. Secondary endpoints include changes in the number of monthly migraine days and headache days, as well as the use of acute migraine medication.

The expected length of participant involvement is up to 36 weeks, with conditions for early termination including the occurrence of serious adverse events or clinically significant changes in health status. Participants will also be monitored for treatment-emergent suicidal ideation or behavior. The end-of-study visit will involve a comprehensive assessment to ensure participant safety and collect final data for analysis. The trial is conducted under strict adherence to ethical guidelines, ensuring that all participants provide informed consent and that their privacy is protected throughout the study.

The clinical trial involves the administration of **IPN10200**, an experimental medication formulated as a **solution for injection**. The active substance in IPN10200 is **Clostridium botulinum, neurotoxin serotype A/B**, which is classified as a protein of other origin. The medication is administered via the **intramuscular route**. The dosing schedule for IPN10200 is structured as a single treatment cycle, with the maximum treatment period being one unit of time, as defined in the study protocol. The specific dosage in nanograms is not detailed in the provided data. Participant compliance with the dosing regimen will be monitored throughout the trial to ensure adherence to the protocol.

In addition to the experimental treatment, the study employs a placebo control, referred to as **IPN10200 placebo**. The placebo is designed to match the experimental medication in appearance and administration method, ensuring the integrity of the double-blind study design. The placebo is also administered intramuscularly, following the same schedule as the active treatment. The use of a placebo allows for the assessment of the efficacy and safety of IPN10200 by providing a baseline for comparison. The trial aims to evaluate the safety, tolerability, and potential immunogenicity of IPN10200, as well as its efficacy in preventing episodic or chronic migraine in adult participants.

The efficacy of IPN10200 in the prevention of episodic or chronic migraine will be assessed through a series of primary and secondary endpoints. The primary efficacy endpoint involves the change from baseline in the number of Monthly Migraine Days (MMDs) at Week 12, specifically during Weeks 9 to 12. This will be measured to determine the effectiveness of IPN10200 compared to placebo.

Secondary efficacy endpoints include the change from baseline in the number of Monthly Headache Days (MHDs) and moderate/severe MHDs, assessed from Week 1 to Week 36. Additionally, the migraine prevention response will be evaluated by a reduction from baseline of either ≥50% or ≥75% in MMDs. Similarly, headache prevention response will be assessed using the same thresholds for MHDs. The change from baseline in the number of days per 4-week period of acute medication use for migraine relief will also be recorded, with an acute medication use day defined as any day on which a participant reports the intake of allowed medication(s) for acute migraine treatment, as documented in the eDiary.

Furthermore, the presence of binding and neutralizing antibodies to IPN10200 will be monitored at baseline, Week 4, Week 12, and Week 36 for Step 1, and additionally at Week 24 for Step 2. These assessments will help determine the immunogenicity of the treatment. The use of validated scales and patient-reported outcomes will be employed to ensure accurate and reliable data collection throughout the trial duration.