Phase 2a Study on Safety, Tolerability, and Pharmacodynamics of OMT-28 in Patients with Primary Mitochondrial Disease-Associated Myopathy/Cardiomyopathy

The primary objective of this Phase 2a study is to evaluate the **responder rate** of patients with Primary Mitochondrial Disease (PMD) who exhibit a decrease of at least 20% in GDF-15 levels after 12 weeks of treatment with OMT-28. This is clinically relevant as GDF-15 is a biomarker associated with mitochondrial dysfunction, and its reduction may indicate therapeutic efficacy in managing myopathy and/or cardiomyopathy with inflammation in PMD patients. Additionally, the study aims to assess the safety and tolerability of OMT-28 at a dosage of 24 mg, which is crucial for determining the risk-benefit profile of the treatment in this patient population.

The clinical trial involves participants diagnosed with **Primary Mitochondrial Disease**, specifically those with documented mutations such as mitochondrial tRNA point mutations (e.g., m3243A>G, m8344A>G) and single mtDNA deletions. The study population includes both male and female subjects aged between 18 to 60 years. Participants are required to have a diagnosis of cardiomyopathy, characterized by left ventricular hypertrophy, left ventricular ejection fraction below 50%, or late gadolinium enhancement on cardiac MRI, or myopathy as defined by established clinical guidelines. The trial does not involve a vulnerable population. Participants must have a GDF-15 level between 1,200 to 10,000 pg/mL at screening and be capable of performing exercise tests. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations include the ability and willingness to comply with study requirements, including the provision of informed consent and adherence to data protection protocols. Female participants and female partners of male participants of childbearing potential must agree to avoid pregnancy throughout the study duration. The selection process ensures that participants are willing and able to meet the study's demands, although specific selection methodologies are not detailed.

The clinical trial is designed as a **Phase II** study to evaluate the safety, tolerability, and pharmacodynamics of the investigational product OMT-28 in patients diagnosed with **Primary Mitochondrial Disease**. The trial employs a randomized, double-blind, controlled methodology to ensure the reliability and validity of the results. The study is expected to span approximately 24 months, with participant involvement lasting up to 6 months. The primary objective is to determine the responder rate of patients exhibiting a decrease of at least 20% in GDF-15 levels after 12 weeks of treatment, alongside assessing the safety and tolerability of OMT-28 at a dosage of 24 mg.

Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, documented mitochondrial disease mutations, and specific clinical parameters. Following successful screening, participants will be randomized to receive either the investigational product or a control. Regular follow-up visits will be scheduled to monitor safety, efficacy, and adherence to the study protocol. These visits will include assessments such as laboratory tests, vital signs, and 12-lead ECGs to evaluate the incidence and severity of any treatment-emergent adverse events (TEAEs).

The end-of-study visit will mark the conclusion of the participant's involvement, during which final evaluations will be conducted to assess the overall impact of the treatment. Participants may be withdrawn from the study prematurely if they experience significant adverse events, fail to comply with the study protocol, or choose to withdraw consent. The trial's design ensures that all data collected will contribute to a comprehensive understanding of the investigational product's effects on the target population.

The clinical trial involves the administration of the experimental medication **OMT-28**, which is formulated as a **capsule**. The active substance in OMT-28 is **2-{[(8Z)-13-[(METHYLCARBAMOYL)FORMAMIDO]-TRIDEC-8-EN-1-YL]OXY}ACETIC ACID**, a synthetic biochemical compound of chemical origin. The medication is provided by OMEICOS THERAPEUTICS GMBH. Each capsule contains 24 mg of the active substance, and the medication is administered orally. The maximum daily dose is 24 mg, with a total maximum dose of 4320 mg over a treatment period of up to 6 months. The trial aims to assess the safety, tolerability, and pharmacodynamic effects of OMT-28 in patients with myopathy and/or cardiomyopathy and inflammation.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of the experimental medication OMT-28. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The trial's main objective is to determine the responder rate of patients with a significant decrease in GDF-15 levels after 12 weeks of treatment, alongside evaluating the safety and tolerability of OMT-28 at the specified dosage.

Efficacy in this clinical trial will be assessed by evaluating the **responder rate** of patients with a between-phase difference in GDF-15 levels, specifically aiming for at least a 20% decrease after 12 weeks of treatment with OMT-28. The primary efficacy endpoint is the number of patients achieving this reduction in GDF-15, a biomarker associated with mitochondrial disease. Measurements of GDF-15 will be conducted at specified intervals to determine the efficacy of the treatment. The trial will focus on patients with documented mitochondrial disease, including those with myopathy and/or cardiomyopathy, and inflammation. The assessment of efficacy will be conducted in a structured manner, ensuring that data collection and analysis are consistent with the trial's objectives.