An Open-label Extension Safety Study of MELAS Patients Who Completed TIS6463-203 (PRIZM)

NCT06961344 | Enrolling By Invitation Phase 2 FDA Drug

• 1 other identifier: TIS6463-204
• Study Type: interventional
• Target: 44
• Locations: 5 countries
• Sites: 16

Brief Summary

The goal of this clinical trial is to evaluate the long-term safety and tolerability of zagociguat in patients with MELAS who completed study medication treatment in the lead-in study TIS6463-203. TIS6463-204 is evaluating zagociguat in an open-label extension study at the daily dose of 15mg. The study medication is a once daily oral table and will be provided at the clinic and/or shipped to the participant's home. Study assessments will be conducted during clinic visits which will occur at three months and then at six months. Thereafter, clinic visits will occur every six months.

Conditions

Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome)

Keywords

MELAS

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-emergent Adverse Events (TEAEs)

  TEAEs are any untoward event that may or may not be related to study medication.

  Day 1 through the Follow-up for treatment period 4 weeks after last dose of study medication.

Study Arms (1)

Zagociguat 15mg

EXPERIMENTAL

Participants receive zagociguat 15 mg once a day (QD) for the duration of the study.

Drug: zagociguat 15mg

Interventions

zagociguat 15mg DRUG

once daily oral tablets

Also known as: IW-6463, CY6463

Zagociguat 15mg

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form (ICF).
• Completed TIS6463-203 treatment through the Period 2 Week 12 Visit.
• Agrees to follow lifestyle restrictions.
• Other criteria per the protocol.

You may not qualify if:

• \. Any medical condition or clinical finding that, per investigator judgement, would preclude safe study participation and/or completion of all trial requirements.

Sponsors & Collaborators

• Tisento Therapeutics: lead

Study Sites (16)

UC San Diego - Altman Clinical and Translational Research Institute

La Jolla, California, 92037, United States

Location

Children's Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

Rare Disease Research

Atlanta, Georgia, 30329, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mount Sinai - Ichan School of Medicine

New York, New York, 10029, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

UT Health Houston

Houston, Texas, 77030, United States

Location

Neuroscience Research Australia

Sydney, New South Wales, NSW 2031, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3052, Australia

Location

LMU Klinikum, Friedrich-Baur-Institute, Department of Neurology

Munich, 80336, Germany

Location

Neurologic Institute Carlo Besta of Milan

Milan, 20133, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Rome, 00168, Italy

Location

University College London Hospital. The National Hospital for Neurology and Neurosurgery, Centre for Neuromuscular Diseases

London, WC1N 3BG, United Kingdom

Location

The Newcastle upon Tyne NHS Foundation Trust

Newcastle upon Tyne, NE14LP, United Kingdom

Location

MeSH Terms

Conditions

Mitochondrial encephalopathy; Acidosis, Lactic; MELAS Syndrome

Condition Hierarchy (Ancestors)

Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Mitochondrial Encephalomyopathies; Mitochondrial Myopathies; Muscular Diseases; Musculoskeletal Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Neuromuscular Diseases; Vascular Diseases; Cardiovascular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: An open-label, single-group assignment extension study. Eligible patients will be entered into a single treatment sequence. The treatment period will last for the shortest of the following: 104 weeks; regulatory approval and commercial availability of zagociguat in the participant's respective country; or termination of the clinical development of zagociguat in MELAS

Study Record Dates

• First Submitted: April 28, 2025
• First Posted: May 7, 2025
• Study Start: August 18, 2025
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); DE (1); IT (2); GB (2); US (9)