Phase 3 Randomized Double-Blind Study of MT-7117 (Dersimelagon Phosphate) in Erythropoietic Protoporphyria and X-Linked Protoporphyria Patients

The primary objective of this study is to evaluate the **efficacy** of MT-7117 in delaying the time to onset and reducing the severity of the first prodromal symptoms, such as burning, tingling, itching, or stinging, associated with sunlight exposure in adults and adolescents with **Erythropoietic Protoporphyria (EPP)** or **X-Linked Protoporphyria (XLP)**. This is clinically relevant as these symptoms significantly impact the quality of life of individuals with these conditions, and effective management could improve patient outcomes.

Secondary objectives include:

• Investigating the effect on the Patient Global Impression of Change (PGIC) in adults and adolescents with EPP or XLP.
• Assessing the effect on the number of sunlight-induced pain events, including prodrome and phototoxic reactions, in the same population.

The clinical trial involves a total of **52 participants** diagnosed with **Erythropoietic Protoporphyria** or **X-Linked Protoporphyria**. The study population includes both male and female subjects, ranging in age from 12 to 75 years. Participants were selected based on their confirmed diagnosis and their ability to comply with the study protocol, including travel to study sites and exposure to sunlight. The trial includes individuals who are considered part of a vulnerable population. Participants are required to have provided informed consent, with additional assent and legal representative consent for minors. Female participants are non-lactating and have tested negative for pregnancy at baseline. Both male and female participants of childbearing potential are using or willing to use two effective methods of contraception. The study does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is a **Phase 3**, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, and tolerability of MT-7117 in adults and adolescents with **Erythropoietic Protoporphyria** or **X-Linked Protoporphyria**. The trial aims to investigate the effect of MT-7117 on the time to onset and severity of first prodromal symptoms associated with sunlight exposure. The study will involve two groups: one receiving MT-7117 Formulation Code C and the other receiving a placebo, both administered orally in tablet form. The trial is expected to last until June 2026, with recruitment starting in March 2024.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and willingness to comply with study requirements. Following the screening, participants will be randomized to receive either the active treatment or placebo. The primary endpoint is the change from baseline in average daily sunlight exposure time to the first prodromal symptom at Week 16. Secondary endpoints include the Patient Global Impression of Change and the total number of sunlight-induced pain events during the 16-week double-blind treatment period.

Study visits will include regular follow-up assessments to monitor safety and efficacy, with the end-of-study visit marking the conclusion of participant involvement. The expected length of participant involvement is up to 52 weeks, with conditions for early termination including non-compliance with study protocol, adverse events, or withdrawal of consent. Participants are required to provide written informed consent, and minors must have assent and legal representative consent. The study is not categorized as low intervention and follows the guidelines for a Phase III trial as per EMA guidance.

The clinical trial involves the administration of **MT-7117 Formulation Code C**, an experimental medication designed to evaluate its efficacy, safety, and tolerability in adults and adolescents with **Erythropoietic Protoporphyria** or **X-Linked Protoporphyria**. The active substance in this formulation is **Dersimelagon Phosphate**, a chemical compound. The pharmaceutical form of MT-7117 is a tablet, and it is administered orally. The dosing schedule is determined by the study protocol, with a maximum treatment period of 52 weeks. The trial ensures participant compliance through regular monitoring and adherence checks.

In addition to the experimental medication, the study employs a placebo control, referred to as **MT-7117 Placebo**. The placebo is designed to match the experimental medication in appearance and administration route, which is oral. The use of a placebo allows for a double-blind study design, ensuring that neither the participants nor the investigators know which treatment is being administered, thereby reducing bias and enhancing the reliability of the study results.

The efficacy of MT-7117 in the treatment of **Erythropoietic Protoporphyria** (EPP) and X-Linked Protoporphyria (XLP) will be assessed through a series of predefined endpoints in a Phase 3, multicenter, randomized, double-blind, placebo-controlled study. The primary endpoint is the change from baseline in the average daily sunlight exposure time to the first prodromal symptom, such as burning, tingling, itching, or stinging, associated with sunlight exposure. This measurement will be taken between 1-hour post-sunrise and 1-hour pre-sunset at Week 16.

Secondary endpoints include the Patient Global Impression of Change (PGIC) at Week 16, the total number of sunlight-induced pain events defined as prodromal symptoms with a pain rating of 1-10 on the Likert scale, and the total number of sunlight-induced non-prodrome, phototoxic reactions during the 16-week double-blind treatment period. These efficacy parameters will be collected and analyzed using validated scales and patient-reported outcomes to ensure accuracy and reliability in the assessment of the treatment's impact on the participants' condition.