Study on the Safety and Effectiveness of Zagociguat for Treating MELAS in Patients

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What is this study about?

This clinical trial is focused on studying a condition called Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS). MELAS is a rare genetic disorder that affects the body’s ability to produce energy, leading to symptoms like muscle weakness, fatigue, and stroke-like episodes. The trial will evaluate the safety and effectiveness of an investigational drug called zagociguat, also known by its code name IW-6463. Zagociguat is taken in tablet form and is being tested to see if it can help improve fatigue and cognitive function, which includes mental processes like thinking and memory, in people with MELAS.

The purpose of this study is to assess how well zagociguat works and how safe it is for patients with MELAS. Participants in the study will receive either zagociguat or a placebo, which looks like the drug but does not contain the active ingredient. The study is designed as a crossover trial, meaning participants will receive both the drug and the placebo at different times during the study. This helps researchers compare the effects of the drug to the placebo. The study will last for about 12 weeks, during which participants will be monitored for any changes in their symptoms and any side effects they might experience.

Throughout the study, participants will undergo various assessments to measure their fatigue levels and cognitive abilities. These assessments include tests like the Groton Maze Learning Test (GMLT) and the International Digit Symbol Substitution Test (iDSST), which help evaluate cognitive function. The study will also track any adverse events, which are any unwanted effects that occur during the trial. By the end of the study, researchers hope to gather enough information to determine if zagociguat is a safe and effective treatment option for people with MELAS.

1 beginning of the trial

Upon joining the study, participants will be randomly assigned to receive either the investigational drug zagociguat or a placebo. A placebo is a tablet that looks like the investigational drug but does not contain the active substance.

The study is designed to be double-blind, meaning neither the participants nor the researchers will know who is receiving the investigational drug or the placebo during the trial.

2 medication administration

Participants will take the assigned tablets orally. The dosage will be either zagociguat 15 mg or zagociguat 7.5 mg, depending on the group assignment.

The tablets are to be taken as directed by the study team, with specific instructions on frequency and duration provided at the start of the trial.

3 monitoring and assessments

Throughout the trial, participants will undergo regular assessments to evaluate the effects of the treatment on fatigue and cognitive function. These assessments include the PROMIS Fatigue MELAS Short Form, Groton Maze Learning Test, and International Digit Symbol Substitution Test.

Participants will also be monitored for any side effects or adverse events that may occur during the study.

4 completion of the trial

At the end of the trial period, participants will have a final visit to assess their overall health and the effects of the treatment.

Participants may be offered the opportunity to continue in an open-label extension study, where all participants receive the investigational drug, if they choose to do so.

Who Can Join the Study?

Must have signed an informed consent form before any study-specific procedures are performed.
If diagnosed with a psychiatric condition like bipolar disorder, anxiety, or depression, must have been stable and on the same treatment for at least 6 months before joining the study.
If female, must either be postmenopausal (no periods for at least 1 year) or surgically sterile, or if of reproductive potential, must not be pregnant or breastfeeding and have negative pregnancy test results.
Male and female participants who can have children must agree to use highly effective birth control methods from the time of signing the consent form until at least 90 days after the last dose of the study drug.
Female participants on hormone replacement therapy must use at least one non-hormonal highly effective birth control method.
Male participants must agree not to donate sperm from the time of the screening visit through 90 days after their last dose of the study drug.
Female participants must agree not to donate eggs for 30 days after the final dose and not to breastfeed through 90 days after the final dose of the study drug.
Must be between 18 to 75 years of age.
Must be diagnosed with MELAS based on specific criteria, including a documented genetic variant and a history of one or more stroke-like episodes with specific MRI findings.
Must be able to complete specific cognitive tests and score below the average on at least one of them during the screening visit.
Must report experiencing fatigue due to MELAS at least sometimes during the screening visit.
Must be able to walk with or without help and complete at least one sit-to-stand movement during a 30-second test.
Must have completed all required at-home activities for at least the final 3 weeks of the screening period and at least one specific test during the screening period.
Must have a platelet count of at least 150,000 platelets per microliter during the screening visit.
Must be on a stable dose of Vitamin D supplement or have a Vitamin D level greater than 30 ng/mL during the screening visit.

Who Cannot Join the Study?

Patients who do not have the condition called Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) cannot participate.
Patients who are not within the specified age range for the study cannot participate.
Patients who are not part of the specified clinical trial group cannot participate.
Patients who are not willing to follow the study procedures cannot participate.
Patients who have other medical conditions that might interfere with the study cannot participate.
Patients who are taking medications that might interfere with the study cannot participate.
Patients who are pregnant or breastfeeding cannot participate.
Patients who have participated in another clinical trial recently cannot participate.
Patients who have a history of drug or alcohol abuse cannot participate.
Patients who have a known allergy to the study medication cannot participate.

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
Rheinische Friedrich-Wilhelms-Universitaet Bonn	Bonn	Germany
Fondazione I.R.C.C.S. Istituto Neurologico Besta	Milan	Italy
Azienda Ospedaliero Universitaria Pisana	Pisa	Italy
Kvnutrrq dpd Ucaafosrtaip Mblgtcip Awp	Munich	Germany

Trial status

Country	Status	Recruitment Start
Germany	Not recruiting	12.11.2024
Italy	Not recruiting	12.11.2024

Trial locations

Investigated drugs:

Zagociguat

Zagociguat is a medication being studied for its potential to help people with a condition called MELAS, which affects energy production in the body. This medication is being tested to see if it can reduce feelings of tiredness and improve thinking abilities in patients with this condition. The study is also looking at how safe and well-tolerated the medication is for those who take it. By participating in this trial, researchers hope to learn more about how zagociguat can benefit people with MELAS and improve their quality of life.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) – This is a genetic disorder that affects the mitochondria, which are the energy-producing structures in cells. It typically begins in childhood and is characterized by muscle weakness and pain, recurrent headaches, loss of appetite, vomiting, and seizures. As the disease progresses, individuals may experience stroke-like episodes that can lead to temporary muscle weakness or paralysis on one side of the body, altered consciousness, and vision abnormalities. Lactic acidosis, a buildup of lactic acid in the body, is also common and can cause nausea, vomiting, and extreme fatigue. Over time, MELAS can lead to progressive neurological and muscular decline, affecting movement and cognitive function. The severity and progression of symptoms can vary widely among individuals.

Trial ID:

2024-515389-15-00

Protocol code:

TIS6463-203

NCT ID:

NCT06402123

Trial Phase:

Therapeutic exploratory (Phase II)

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Study on the Safety and Effectiveness of Zagociguat for Treating MELAS in Patients

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