Long-term Safety and Tolerability Evaluation of Oral Dersimelagon (MT-7117) in Erythropoietic Protoporphyria and X-Linked Protoporphyria Patients

The primary objective of this Phase 3, multicenter, open-label, long-term extension study is to evaluate the **long-term safety** and **tolerability** of oral Dersimelagon (MT-7117) in subjects diagnosed with **Erythropoietic Protoporphyria (EPP)** or **X-Linked Protoporphyria (XLP)**. Assessing the safety and tolerability of this treatment is clinically relevant as it provides essential data on the potential adverse effects and overall patient tolerance to the medication over an extended period, which is crucial for determining its suitability for long-term use in managing these conditions.

The clinical trial involves a total of **112 participants** diagnosed with **Erythropoietic Protoporphyria (EPP)** or **X-Linked Protoporphyria (XLP)**. The study population includes both male and female subjects, ranging in age from 12 to 75 years. Participants were selected based on their completion of previous studies, specifically MT-7117-G01, MT-7117-A-302, or MT-7117-A-301, and their ability to comply with study requirements. The trial includes individuals who are considered a vulnerable population. Participants are required to have a body weight above a specified threshold and must be willing to travel to study sites for scheduled visits. Female participants must be non-lactating and have a negative pregnancy test at baseline. Both male and female participants of childbearing potential are required to use effective contraception methods. The trial aims to evaluate the long-term safety and tolerability of oral MT-7117.

The clinical trial is designed as a **Phase 3**, multicenter, open-label, long-term extension study to evaluate the safety and tolerability of oral **dersimelagon phosphate** in subjects with **Erythropoietic Protoporphyria (EPP)** or **X-Linked Protoporphyria (XLP)**. The trial will involve participants who have completed previous studies (MT-7117-G01, MT-7117-A-302, or MT-7117-A-301) and meet specific inclusion criteria, such as age between 12 and 75 years and a confirmed diagnosis of EPP or XLP. The study will not be blinded, and all participants will receive the investigational product, MT-7117 Formulation Code C, administered orally in tablet form. The trial is expected to run until December 30, 2027, with recruitment having started on April 13, 2022.

Participants will be involved in the study for a maximum treatment period of 286 days. The study visits will include an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor safety and tolerability. The primary endpoints include the assessment of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs). Additional evaluations will include physical examinations, vital signs, clinical laboratory tests, 12-lead electrocardiograms (ECGs), and dermatological assessments of nevi. The end-of-study visit will conclude the participant's involvement, with a comprehensive evaluation of safety parameters.

Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with the study protocol, or withdraw consent. The study aims to provide valuable data on the long-term safety profile of dersimelagon phosphate in the target population, contributing to the understanding of its use in managing EPP and XLP. The trial is categorized as a non-low intervention study, reflecting its comprehensive safety monitoring and data collection requirements.

The clinical trial involves the administration of the experimental medication **MT-7117 Formulation Code C**, which contains the active substance **dersimelagon phosphate**. This medication is provided in the form of a **tablet** and is intended for **oral use**. The trial aims to evaluate the long-term safety and tolerability of this medication in subjects with Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP). The maximum treatment period for the study is 286 days. The medication is of chemical origin and is not a pediatric formulation. The dosing schedule, including the specific dosage and frequency of administration, is not explicitly detailed in the provided data.

In addition to the experimental treatment, the study may include non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments, although specific details regarding these are not provided in the data. Participant compliance with the dosing regimen will be monitored throughout the study to ensure adherence to the protocol. The trial is conducted under the sponsorship of Mitsubishi Tanabe Pharma America, Inc., and the medication has been designated as an orphan drug, indicating its use for a rare condition. The study is open-label, meaning that both the researchers and participants are aware of the treatment being administered.

Efficacy in the clinical trial will be assessed through a series of primary endpoints designed to evaluate the safety and tolerability of oral **Dersimelagon** (MT-7117) in subjects with Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP). The primary endpoints include the monitoring of treatment-emergent adverse events (TEAEs), which encompass serious adverse events (SAEs) and adverse events of special interest (AESIs). Additionally, physical examinations, vital signs (including blood pressure, respiratory rate, pulse rate, and body temperature), and clinical laboratory examinations will be conducted. These laboratory tests will cover hematology, coagulation, biochemistry, and urinalysis, with a specific focus on liver function markers such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and bilirubin levels.

Furthermore, 12-lead electrocardiogram (ECG) parameters will be evaluated to monitor cardiac health. The appearance of nevi will also be assessed by a dermatologist or other qualified site staff, with any nevi undergoing changes of clinical concern during active treatment being biopsied for follow-up and evaluated by a central pathology lab. These assessments will be conducted at various timepoints throughout the study to ensure comprehensive monitoring of the subjects' health and the efficacy of the treatment.