Long-term safety study of zagociguat tablets in patients with MELAS syndrome (Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) who completed previous trial

2 1 1

What is this study about?

This study focuses on people with MELAS (Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), which is a rare genetic condition that affects the body’s energy production in cells, leading to various symptoms including muscle weakness, neurological problems, and stroke-like episodes. The study will evaluate a medication called zagociguat, given as a 15 mg tablet taken by mouth.

The main purpose of this research is to assess the long-term safety of zagociguat in patients who have already completed a previous study of this medication. This is an open-label extension study, which means all participants will receive the active medication without use of a placebo.

The study will continue for approximately 156 weeks (3 years), during which participants will take the medication daily. Throughout the study, doctors will monitor participants’ health through various medical examinations and tests to ensure their safety and evaluate how well they tolerate the medication over an extended period.

1 Initial medication period

You will receive zagociguat tablets (15 mg) for oral use. This medication is intended for long-term treatment.

The treatment begins after completing the previous TIS6463-203 study through Period 2 Week 12 visit.

2 Regular health assessments

Your vital signs will be monitored at scheduled appointments.

You will undergo ECG (heart rhythm tests) at scheduled visits.

Regular laboratory tests will be conducted to monitor your health.

Your bone density will be measured using DEXA scan of hip and spine at specified intervals.

Blood tests will be performed to measure various biological markers.

Your overall condition will be evaluated using specific assessment scales.

3 Safety monitoring

Any side effects or health changes will be recorded throughout the study.

Your kidney function will be monitored through specific tests.

Heart-related proteins will be measured in your blood.

The amount of medication in your blood will be checked at scheduled timepoints.

4 Study duration

The study is expected to run from September 2025 to August 2027.

You will need to follow specific safety guidelines throughout the study period.

Female participants must avoid egg donation for 30 days after the last dose.

Male participants must avoid sperm donation for 90 days after the last dose.

Who Can Join the Study?

Must sign an approved informed consent form before starting any study procedures
Must have completed the previous TIS6463-203 treatment through Week 12
For female participants:
- Must be either post-menopausal (no menstrual periods for at least 1 year) or surgically unable to have children (through removal of ovaries, uterus, or fallopian tube procedures), OR
- If able to have children, must not be pregnant and have negative pregnancy tests during screening
For participants who can have children (both men and women):
- Must either completely avoid heterosexual intercourse, OR
- Must use highly effective birth control methods such as:
  - Hormonal contraception (pills, vaginal rings, or skin patches)
  - IUD (intrauterine device)
  - Have permanent sterilization procedures
  - Be in a relationship with a partner who is permanently unable to have children
Women using hormone replacement therapy must use additional non-hormonal birth control
Male participants cannot donate sperm from screening through 90 days after the last dose
Female participants cannot donate eggs through 30 days after the last dose

Who Cannot Join the Study?

Age below 18 years or above 65 years
Not having a confirmed diagnosis of MELAS syndrome (a rare genetic disorder affecting energy production in cells)
Pregnancy or breastfeeding
History of severe allergic reactions to medications
Current participation in other clinical trials
Significant kidney or liver problems
Uncontrolled high blood pressure
Recent stroke or heart attack (within the last 6 months)
Active cancer or ongoing cancer treatment
Severe mental health conditions that could affect ability to follow study procedures
Use of medications that could interact with the study drug zagociguat
Unable to provide informed consent
History of non-compliance with medical treatments
Conditions that could interfere with study medication absorption
Unstable medical conditions that could affect safety during the trial

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Italy

Other Sites

Site Name	City	Country
Universita’ Di Pisa	Pisa	Italy
Rheinische Friedrich-Wilhelms-Universitaet Bonn	Bonn	Germany
Fondazione I.R.C.C.S. Istituto Neurologico Besta	Milan	Italy
Ktdlkeyl dkj Utxgkofyqsst Msanknii Acz	Munich	Germany

Trial status

Country	Status	Recruitment Start
Germany	Not yet recruiting	01.09.2025
Italy	Not yet recruiting	01.09.2025

Trial locations

Investigated drugs:

Zagociguat

Zagociguat is an investigational medication being studied for patients with MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes). This medication is being evaluated to understand its long-term safety and how well patients can tolerate it. It is designed to help patients who have already participated in a previous study of the same medication. The drug is still in the research phase, and researchers are particularly interested in monitoring how safe it is when used over an extended period.

Investigated diseases:

MELAS syndrome

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) – A rare genetic disorder that affects the body’s energy production at the cellular level. The condition primarily affects the brain, nervous system, and muscles. MELAS typically begins in childhood and is characterized by stroke-like episodes that can cause temporary weakness on one side of the body, altered consciousness, and headaches. People with MELAS experience a buildup of lactic acid in their bodies, which can lead to muscle weakness, exercise intolerance, and fatigue. The disease also affects multiple organs and can cause hearing loss, diabetes, and muscle weakness.

Trial ID:

2024-517514-15-00

Protocol code:

TIS6463-204

NCT ID:

NCT06961344

Trial Phase:

Therapeutic exploratory (Phase II)

Other Trials to Consider

#1 Clinical Trials Search in Europe

Long-term safety study of zagociguat tablets in patients with MELAS syndrome (Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) who completed previous trial

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?