Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome) Clinical Trial
— PRIZMOfficial title:
Phase 2b Randomized, Double-blind, Placebo-controlled Crossover Study Evaluating the Efficacy and Safety of Zagociguat in Participants With MELAS (PRIZM)
| Verified date | June 2024 |
| Source | Tisento Therapeutics |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
PRIZM is a Phase 2b randomized, double-blind, placebo-controlled, 3-treatment, 2-period, crossover study evaluating the efficacy and safety of oral zagociguat 15 and 30 mg vs. placebo when administered daily for 12 weeks in participants with genetically and phenotypically defined MELAS.
| Status | Not yet recruiting |
| Enrollment | 36 |
| Est. completion date | September 1, 2025 |
| Est. primary completion date | September 1, 2025 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 75 Years |
| Eligibility | 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 composite memory score from One Back and One Card Learning tests. 5. Reports fatigue due to MELAS. 6. Can complete at least 1 sit-to-stand in the 30-second test interval. 7. Complete all at-home weekly activities during the Screening Period. 8. Other criteria per the protocol. Exclusion Criteria: 1. Severe visual impairment that precludes ability to complete cognitive performance tests independently. Note: a caregiver can provide support throughout the study. 2. Systolic blood pressure (BP) 90 mmHg or diastolic BP 60 mmHg. 3. Orthostatic hypotension when measured after standing from a semi-recumbent/supine position. 4. Active cancer significant enough to confound the results of this study. 6. 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. 7. History of spontaneous fracture(s) that in the investigator's opinion represents a safety risk for trial participation. 8. Current use of prohibited medication (reviewed by investigator). 9. Any medical or other condition that the investigator think would preclude study participation. 10. Other exclusion criteria per protocol. |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Royal Melbourne Hospital | Melbourne | Victoria |
| Australia | Neuroscience Research Australia | Sydney | New South Wales |
| Canada | Winnipeg Children's Hospital | Winnipeg | |
| Germany | University Hospital Bonn | Bonn | |
| Germany | Ludwig-Maximilians-University of Munich | Munich | |
| Italy | Neurologic Institute Carlo Besta of Milan | Milan | |
| Italy | University of Pisa Neurological Clinic | Pisa | |
| Italy | Fondazione Policlinico Universitario Agostino Gemelli | Roma | |
| United Kingdom | UCL Queen Square Institute of Neurology | London | |
| United Kingdom | Newcastle University | Newcastle Upon Tyne | |
| United States | Akron Children's Hospital | Akron | Ohio |
| United States | Rare Disease Research | Atlanta | Georgia |
| United States | Children's Hospital of Colorado | Aurora | Colorado |
| United States | Johns Hopkins University School of Medicine | Baltimore | Maryland |
| United States | Massachusetts General Hospital | Boston | Massachusetts |
| United States | Baylor College of Medicine | Houston | Texas |
| United States | University of Texas Medical School at Houston | Houston | Texas |
| United States | UC San Diego - Altman Clinical and Translational Research Institute | La Jolla | California |
| United States | Columbia University Irving Medical Center | New York | New York |
| United States | Mount Sinai - Ichan School of Medicine | New York | New York |
| United States | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania |
| United States | University of Pittsburgh | Pittsburgh | Pennsylvania |
| United States | Mayo Clinic Rochester | Rochester | Minnesota |
| United States | Children's National | Washington | District of Columbia |
| Lead Sponsor | Collaborator |
|---|---|
| Tisento Therapeutics |
United States, Australia, Canada, Germany, Italy, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | • PROMIS Fatigue MELAS Short Form scores • Memory composite scores (One Card Learning and One Back Tests) • International Digit Symbol Substitution Test scores | These measures are a patient reported questionnaire on MELAS-specific fatigue and 3 cognitive performance tests. These 3 outcome measures will be combined into a single primary outcome measure using a global statistical test. | Weeks 9 through 12 of each treatment period | |
| Primary | Incidence of Treatment-emergend Adverse Events (TEAEs) | TEAEs are any untoward event that may or may not be related to study medication. | Weeks 1 through washout for treatment period 1 and Weeks 1 through follow-up for treatment period 2 | |
| Secondary | Number of repetitions completed during the 30-second sit-to-stand test | Leg strength and exercise intolerance | Week 12 | |
| Secondary | Groton Maze Learning Test (GMLT) scores | Test of executive function | Week 9 through 12 | |
| Secondary | PROMIS Cognitive Function MELAS Short Form (PCFM-SF) score | Patient-reported questionnaire on MELAS-specific cognitive function | Week 12 | |
| Secondary | Plasma concentrations of GDF-15 | Measure of disease pathophysiology | Week 12 |