A Phase 2b Study of Zagociguat in Patients With MELAS

The goal of this clinical trial is to learn about the effectiveness of zagociguat in patients with MELAS. The main questions it aims to answer are: * Does zagociguat improve fatigue in patients with MELAS? * Does zagociguat improve cognitive performance in patients with MELAS? * What is the safety and tolerability profile of zagociguat? The PRIZM study is evaluating 2 dose levels of zagociguat in a crossover design consisting of two 12-week treatment periods separated by a 4-week washout. Patients will be screened and if eligible, randomly assigned either to receive placebo in period 1 followed by active drug in period 2 OR to receive active drug in period 1 followed by placebo in period 2. Study medication is a once daily oral tablet and will be provided at the clinic and/or shipped to the participant's home. Clinic visits will occur at screening and Week 1 and Week 12 of each treatment period. Visits at Week 4 and Week 8 of both crossover periods will either be in clinic or optionally at the participant's home. Study assessments will be conducted weekly on a phone app and a separate tablet and additional assessments will be conducted during visits. Patients who complete the study will be eligible for an open label extension study.