Thiogenesis Therapeutics has received the final regulatory clearance from the European Medicines Agency (EMA) to commence its Phase 2 clinical trial of TTI-0102 for the treatment of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). This clearance allows Thiogenesis to initiate the multi-center trial in leading institutions across France and the Netherlands.
The Phase 2 trial is designed as a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics, and efficacy of orally administered TTI-0102 in MELAS patients over a 6-month period. The trial will enroll a total of 12 patients, with 8 receiving TTI-0102 and 4 receiving a placebo.
Trial Design and Endpoints
The Phase 2 trial will include an interim analysis of safety data, pharmacokinetics/pharmacodynamics, and key biomarkers such as cysteamine, glutathione, and taurine after 3 months. In addition to biomarker assessments, the trial's efficacy endpoints include:
- 12-Minute Walking Test (12-MWT)
- Fatigue Severity Scale (FSS)
- Quality of Life Assessment (WHOQOL-BREF)
TTI-0102: A Novel Approach to MELAS Treatment
TTI-0102, Thiogenesis' lead compound, is an asymmetric disulfide and a prodrug of cysteamine. It is designed to increase intracellular levels of the antioxidant glutathione and the amino acid taurine, both of which are known to be deficient in MELAS patients. According to Patrice Rioux, MD, Ph.D., CEO of Thiogenesis, TTI-0102 has the potential to be a viable therapeutic compound for MELAS, a condition for which there are currently no approved drugs.
About MELAS
MELAS is a rare, inherited mitochondrial disorder affecting an estimated 4.4 per 100,000 individuals. It is most often caused by a mutation of m.3243A>G in the MT-TL1 gene in mitochondrial DNA. The disease typically presents before age 20 with symptoms including seizures, vomiting, headaches, muscle weakness, loss of appetite, and fatigue. Over time, MELAS can lead to loss of motor skills and intellectual disability. Oxidative stress and taurine deficiency are implicated in the pathology of MELAS, making them potential therapeutic targets.
