Zagociguat for MELAS Syndrome

Enrolling by invitation at 7 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Tisento Therapeutics

Disqualifiers: Others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: Ongoing with clinic visits at 3 months, 6 months, and every 6 months thereafter

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the long-term safety and tolerability of zagociguat for individuals with MELAS syndrome, a rare condition affecting cellular energy production. Participants will take a 15 mg dose of zagociguat daily, available for pickup at the clinic or delivery to their home. Eligible participants should have completed the initial study phase and be willing to adhere to specific lifestyle guidelines. Clinic visits will occur every few months to monitor progress. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to important findings.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that zagociguat is likely to be safe for humans?

Research has shown that zagociguat has been tested for safety in people with MELAS syndrome, a rare genetic condition. One study examined the safety and tolerability of zagociguat in these patients and found it to be generally safe. No serious safety issues have been reported in these studies.

Earlier research also tested zagociguat in animals, such as zebrafish, with promising safety results. This supports the idea that it might be safe for humans as well.

Since this trial is a Phase 2 trial, the treatment has already passed initial safety tests in earlier phases. This suggests it is likely to be well-tolerated, but researchers continue to ensure its safety for long-term use in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for MELAS?

Most treatments for MELAS syndrome focus on managing symptoms, but zagociguat offers a different approach by targeting the underlying energy production issues in cells. Researchers are excited about zagociguat because it works by enhancing the nitric oxide signaling pathway, which may improve mitochondrial function and energy production. This novel mechanism could potentially address the root cause of MELAS syndrome, offering hope for more effective long-term management of the condition.

What evidence suggests that zagociguat might be an effective treatment for MELAS?

Research has shown that zagociguat might help treat MELAS syndrome. This drug targets the mitochondria, the cell's power plants. In people with MELAS, these power plants malfunction, causing symptoms like muscle weakness and headaches. Zagociguat aims to improve mitochondrial function, potentially reducing symptoms. Early results suggest that patients taking zagociguat experienced some improvements. However, further research is needed to fully understand its effectiveness. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for patients with MELAS Syndrome who finished the TIS6463-203 study. Participants must have signed a consent form, agree to lifestyle restrictions, and meet other protocol criteria.

Inclusion Criteria

I completed the TIS6463-203 treatment up to Week 12.

I have signed the consent form approved by the ethics committee.

I agree to follow specific lifestyle changes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive zagociguat 15 mg once a day for the duration of the study

Ongoing with clinic visits at 3 months, 6 months, and every 6 months thereafter

Clinic visits at 3 months, 6 months, and every 6 months thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• zagociguat

Trial Overview The trial tests the long-term safety of zagociguat at a daily dose of 15mg in MELAS patients. It's an open-label extension where participants take an oral tablet every day and attend clinic visits initially every three months, then every six months.

How Is the Trial Designed?

Group I: Zagociguat 15mg Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Tisento Therapeutics

Lead Sponsor

Trials

6

Recruited

250+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06402123

A Phase 2b Study of Zagociguat in Patients With MELAS A phase of research to describe clinical trials that gather more information about a drug's safety and effectiveness by studying different populations and ...

2. trialx.com trialx.com/clinical-trials/listings/297461/a-phase-2b-study-of-zagociguat-in-patients-with-melas/

A Phase 2b Study of Zagociguat in Patients With MELAS The goal of this clinical trial is to learn about the effectiveness of zagociguat in patients with MELAS. The main questions it aims to answer ...

3. clinicaltrialsarena.com clinicaltrialsarena.com/news/tisento-study-zagociguat-melas/

Tisento doses first subject in Phase IIb study of zagociguat ... Tisento doses first subject in Phase IIb study of zagociguat for MELAS treatment. The trial is offering at-home evaluations, the possibility of ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06402123?term=AREA%5BConditionSearch%5D(Melas%20syndrome%20OR%20%22mitochondrial%20encephalomyopathy,%20lactic%20acidosis%20and%20stroke%22%20OR%20%22%20mitochondrial%20encephalomyopathy,%20lactic%20acidosis%20and%20stroke-like%20episodes%22%20OR%20%22%20mitochondrial%20myopathy,%20encephalopathy,%20lactic%20acidosis%20and%20stroke-like%20episodes%22%20OR%20%22%20mitochondrial%20myopathy,%20encephalopathy,%20lactic%20acidosis,%20and%20stroke-like%20episodes%22)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING)&rank=7

A Phase 2b Study of Zagociguat in Patients With MELAS PRIZM is a Phase 2b randomized, double-blind, placebo-controlled, 3-treatment, 2-period, crossover study evaluating the efficacy and safety of oral zagociguat ...

5. uth.trialstoday.org uth.trialstoday.org/list/print/NCT06402123

A Phase 2b Study of Zagociguat in Patients With MELAS PRIZM is a Phase 2b randomized, double-blind, placebo-controlled, 3-treatment, 2-period, crossover study evaluating the efficacy and safety of ...

6. chop.edu chop.edu/news/childrens-hospital-philadelphia-researchers-find-promising-preclinical-data-expanding-use-drug

Children's Hospital of Philadelphia ... Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) syndrome – was safe and effective in multiple preclinical zebrafish models.

7. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-of-zagociguat-for-patients-with-melas-syndrome/

Long-term safety study of zagociguat tablets in patients ... This study examines the long-term safety and tolerability of Zagociguat, also known as IW-6463, in treating patients with Mitochondrial ...

8. go.drugbank.com go.drugbank.com/drugs/DB18315/clinical_trials?conditions=DBCOND0133949&phase=2&purpose=treatment&status=enrolling_by_invitation

Zagociguat Enrolling by Invitation Phase 2 Trials for ... Zagociguat Enrolling by Invitation Phase 2 Trials for Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke Like Episodes (MELAS) Treatment ; NCT06961344.