Active not recruitingPHASE2INTERVENTIONAL

A Phase 2b Study of Zagociguat in Patients With MELAS

The PRIZM study is a research trial exploring a new medication called zagociguat for individuals diagnosed with MELAS syndrome (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes). The main goals are to find out if zagociguat can improve problems like tiredness (fatigue) and thinking difficulties often experienced by people with MELAS. Researchers also want to check how safe the medicine is and if people can tolerate taking it. Participants will take an oral tablet daily for 12 weeks, followed by a break, and then another 12 weeks of treatment. Some will start with the active medicine and then switch to a dummy pill (placebo), while others will do the reverse. This approach helps researchers understand the medicine's effects better.

At a glance

Status

Active not recruiting

Phase

PHASE2

Sponsor

Tisento Therapeutics

Enrolment target

Start

10 Sep 2024

Estimated completion

20 Jun 2026

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

What is this study about?

This research study, called PRIZM, is looking into a new medicine called zagociguat for people who have MELAS syndrome. MELAS is a serious condition that affects the body's energy-producing parts (mitochondria), leading to symptoms like tiredness, problems with thinking and memory, and stroke-like episodes. The study wants to see if zagociguat can make a real difference in these symptoms and help people feel better. It's a 'Phase 2b' study, which means it's one of the earlier steps in testing a new medicine, focusing on finding the right dose and checking for safety.

The main questions this study hopes to answer are whether zagociguat can improve how tired people with MELAS feel, if it can help with their thinking and memory skills, and importantly, if it is safe to use and doesn't cause too many side effects. By carefully studying these things, doctors hope to find new ways to help manage MELAS syndrome and improve the quality of life for those living with it.

To get clear results, the study uses a 'crossover' design. This means that each participant will get to try both the actual medicine and a dummy pill (placebo) at different times during the study. This helps the researchers compare the effects of the medicine fairly. All participants will be closely monitored by a healthcare team throughout the study to ensure their safety and track any changes in their health.

Key takeaways

Tests new medicine (zagociguat) for MELAS symptoms like tiredness and thinking.
Compares zagociguat to a dummy pill (placebo) over two 12-week periods.
Participants take a daily tablet and have clinic visits, plus home assessments.
Focuses on safety and effectiveness, including any side effects.
You can withdraw from the study at any time.
The study aims to improve understanding and treatment options for MELAS.

Who may be eligible?

To join this study, you need to be a man or a woman between 18 and 75 years old. You must have a confirmed diagnosis of MELAS syndrome, which means doctors have found a specific genetic change linked to MELAS and you've had stroke-like episodes that show up on a brain scan. Also, you should be experiencing fatigue (tiredness) due to your MELAS, and have some difficulty with certain thinking and memory tests.

You also need to be able to do some light physical activity, like standing up from a chair at least once in 30 seconds. You should be able to manage weekly tasks on a phone app or tablet mostly on your own, though someone can help you set up the devices. You'll need to sign a consent form, showing you understand the study and agree to take part.

There are also some reasons why you might not be able to join. These include having very high or very low blood pressure, certain bleeding problems, uncontrolled cancer, severe stomach or bowel issues, or any other health problem that your study doctor thinks would make it unsafe for you to participate or would affect the study results.

Quick self-check

Are you between 18 and 75 years old?
Do you have a confirmed diagnosis of MELAS, including specific genetic changes and stroke-like episodes?
Do you experience tiredness (fatigue) due to your MELAS?
Can you do weekly activities on a phone or tablet independently (with setup help)?
Are your blood pressure and other general health indicators within a safe range to participate?
Have you discussed any current medications with your doctor to ensure they are allowed in the study?

This is a guide only — the research team will confirm whether you can take part.

What does participation involve?

If you decide to take part, you'll first have a screening visit to check if you're suitable. If you are, you'll be randomly assigned to one of two groups. One group will take the active medicine for 12 weeks, then have a 4-week break, and then take a dummy pill for another 12 weeks. The other group will do this in reverse. The study medicine is a tablet you'll take once a day, either provided at the clinic or sent to your home.

You'll have clinic visits at the start, and at Week 1 and Week 12 of each 12-week treatment period. Other visits at Week 4 and Week 8 can be at the clinic or potentially at your home. You'll also use a phone app and a separate tablet to do weekly assessments at home. After you complete the main study, you might be able to join an 'open-label extension study,' where everyone receives the active medicine. The total duration of the main study will be about 28 weeks (12 weeks treatment, 4 weeks break, 12 weeks treatment).

Potential risks and benefits

Taking part in a study like this might have potential benefits, such as closely monitoring your health and possibly experiencing an improvement in your MELAS symptoms if zagociguat is effective. However, it's also possible you might not feel any improvement, especially if you receive the dummy pill. There could be potential risks, including side effects from the study medication, though these will be closely monitored. You will be told about any known side effects before you decide to take part. Remember, participation is always voluntary, and you have the right to withdraw from the study at any time, for any reason, without it affecting your usual medical care.

Locations (20)

UC San Diego - Altman Clinical and Translational Research Institute
La Jolla, United States
Children's Hospital of Colorado
Aurora, United States
Rare Disease Research
Atlanta, United States
Massachusetts General Hospital
Boston, United States
Columbia University Irving Medical Center
New York, United States
Mount Sinai - Ichan School of Medicine
New York, United States
Akron Children's Hospital
Akron, United States
Children's Hospital of Philadelphia
Philadelphia, United States
Baylor College of Medicine
Houston, United States
University of Texas Medical School at Houston
Houston, United States
Neuroscience Research Australia
Sydney, Australia
Royal Melbourne Hospital
Melbourne, Australia

+8 more sites — see the official record for the full list.

Common questions

What is MELAS syndrome?

MELAS syndrome is a rare genetic disorder that affects the body's energy-making process, leading to symptoms like tiredness, muscle weakness, headaches, and sometimes stroke-like episodes.

What is a 'dummy pill' or placebo?

A dummy pill (placebo) looks exactly like the study medicine but contains no active drug. It's used to compare the effects of the real medicine more accurately.

Will I know if I'm getting the real medicine or the dummy pill?

No, this is a 'double-blind' study, meaning neither you nor your study doctors will know who is receiving the active medicine and who is receiving the dummy pill until after the study is over. This helps ensure fair and unbiased results.

What kind of tests will I have during the study?

You'll have regular medical checks, possibly blood tests, and assessments of your tiredness and thinking abilities. You'll also use apps to track your health at home.

Can I leave the study at any time?

Yes, you are completely free to leave the study at any point, for any reason, and it will not affect your relationship with your doctors or your future medical care.