Evaluating zagociguat for treating MELAS syndrome
Phase 2b Randomized, Double-blind, Placebo-controlled Crossover Study Evaluating the Efficacy and Safety of Zagociguat in Participants With MELAS (PRIZM)
This study is testing if a new oral medication called zagociguat can help people with MELAS syndrome feel less tired and think better.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 44 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Tisento Therapeutics Industry-sponsored |
| Locations | 25 sites (La Jolla, California and 24 other locations) |
| Trial ID | NCT06402123 on ClinicalTrials.gov |
What this trial studies
This clinical trial is a Phase 2b randomized, double-blind, placebo-controlled study assessing the efficacy and safety of oral zagociguat in patients with MELAS. Participants will receive either zagociguat at two different doses or a placebo over two 12-week treatment periods, separated by a 4-week washout. The study aims to determine if zagociguat can improve fatigue and cognitive performance in these patients while also evaluating its safety and tolerability. Participants will engage in regular assessments through clinic visits and a mobile app to monitor their progress.
Who should consider this trial
Good fit: Ideal candidates for this study are adults aged 18 to 75 diagnosed with MELAS who experience fatigue and have specific genetic markers.
Not a fit: Patients with severe gastrointestinal issues or significant active cancer may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could significantly improve the quality of life for patients suffering from MELAS by alleviating fatigue and enhancing cognitive function.
How similar studies have performed: While this approach is novel for MELAS, similar studies targeting mitochondrial disorders have shown promising results.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: 1. Signed consent form. 2. 18 to 75 years of age. 3. Diagnosed with MELAS based on the presence of each of the following criteria: 1. A documented pathogenic variant in a mitochondrial DNA (mtDNA) gene. 2. History of one or more stroke-like episodes (SLEs) with magnetic resonance imaging (MRI) findings consistent with stroke-like lesions. 4. Scores below normal average on the iDSST and GMLT. 5. Reports fatigue due to MELAS. 6. Can complete at least 1 sit-to-stand in the 30-second test interval. 7. Completes all at-home weekly activities independently during the Screening Period (caregiver may help set up device/app, log-in, etc.). 8. Other criteria per the protocol. Exclusion Criteria: 1. Systolic blood pressure (BP) 90 mmHg or diastolic BP 60 mmHg. 2. Orthostatic hypotension when measured after standing from a semi-recumbent/supine position. 3. Active cancer significant enough to confound the results of this study. 4. Severe gastrointestinal dysmotility that may impact participation. 5. 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. 6. History of spontaneous fracture(s) that in the investigator's opinion represents a safety risk for trial participation. 7. Current use of prohibited medication (reviewed by investigator). 8. Any medical or other condition that the investigator thinks would preclude study participation. 9. Other exclusion criteria per protocol.
Where this trial is running
La Jolla, California and 24 other locations
- UC San Diego - Altman Clinical and Translational Research Institute — La Jolla, California, United States (Recruiting)
- Children's Hospital of Colorado — Aurora, Colorado, United States (Recruiting)
- Children's National — Washington, District of Columbia, United States (Recruiting)
- Rare Disease Research — Atlanta, Georgia, United States (Recruiting)
- Johns Hopkins University School of Medicine — Baltimore, Maryland, United States (Recruiting)
- Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)
- Mayo Clinic Rochester — Rochester, Minnesota, United States (Recruiting)
- Columbia University Irving Medical Center — New York, New York, United States (Recruiting)
- Mount Sinai - Ichan School of Medicine — New York, New York, United States (Recruiting)
- Akron Children's Hospital — Akron, Ohio, United States (Recruiting)
- Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (Recruiting)
- UPMC Children's Hospital of Pittsburgh — Pittsburgh, Pennsylvania, United States (Recruiting)
- Baylor College of Medicine — Houston, Texas, United States (Recruiting)
- University of Texas Medical School at Houston — Houston, Texas, United States (Recruiting)
- Neuroscience Research Australia — Sydney, New South Wales, Australia (Recruiting)
- Royal Melbourne Hospital — Melbourne, Victoria, Australia (Recruiting)
- Shared Health/University of Manitoba — Winnipeg, Manitoba, Canada (Recruiting)
- McMaster University Medical Center — Hamilton, Ontario, Canada (Recruiting)
- University Hospital Bonn — Bonn, Germany (Recruiting)
- Ludwig-Maximilians-University of Munich — Munich, Germany (Recruiting)
- Neurologic Institute Carlo Besta of Milan — Milan, Italy (Recruiting)
- University of Pisa Neurological Clinic — Pisa, Italy (Recruiting)
- Fondazione Policlinico Universitario Agostino Gemelli — Roma, Italy (Recruiting)
- UCL Queen Square Institute of Neurology — London, United Kingdom (Recruiting)
- Newcastle University — Newcastle Upon Tyne, United Kingdom (Recruiting)
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.