A Phase 2b Study of Zagociguat in Patients With MELAS

Prior treatment

• Current use of prohibited medication (reviewed by investigator).

Other illness

• Active cancer significant enough to confound the results of this study.
• History of spontaneous fracture(s) that in the investigator's opinion represents a safety risk for trial participation.
• Any medical or other condition that the investigator thinks would preclude study participation.

Lab values

• Recent history (within last 6 months) of platelet dysfunction, hemophilia, von Willebrand disease, coagulation disorder, other bleeding diathesis condition(s), or significant, nontraumatic bleeding episodes.

Other

• Systolic blood pressure (BP) 90 mmHg or diastolic BP 60 mmHg.
• Orthostatic hypotension when measured after standing from a semi-recumbent/supine position.
• Severe gastrointestinal dysmotility that may impact participation.
• Other exclusion criteria per protocol.

• Signed consent form.
• 18 to 75 years of age.
• Diagnosed with MELAS based on the presence of each of the following criteria:
  • A documented pathogenic variant in a mitochondrial DNA (mtDNA) gene.
  • History of one or more stroke-like episodes (SLEs) with magnetic resonance imaging (MRI) findings consistent with stroke-like lesions.
• Scores below normal average on the iDSST and GMLT.
• Reports fatigue due to MELAS.
• Can complete at least 1 sit-to-stand in the 30-second test interval.
• Completes all at-home weekly activities independently during the Screening Period (caregiver may help set up device/app, log-in, etc.).
• Other criteria per the protocol.