44 Participants Needed

Zagociguat for MELAS Syndrome

(PRIZM Trial)

Recruiting at 26 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 1 JurisdictionThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

PRIZM is a Phase 2b randomized, double-blind, placebo-controlled, 3-treatment, 2-period, crossover study evaluating the efficacy and safety of oral zagociguat 15 and 30 mg vs. placebo when administered daily for 12 weeks in participants with genetically and phenotypically defined MELAS.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that current use of prohibited medication will be reviewed by the investigator. It's best to discuss your medications with the trial team.

What data supports the effectiveness of the drug Zagociguat for MELAS Syndrome?

Zagociguat is a drug that has been shown to be well-tolerated and can penetrate the central nervous system, which is important for treating brain-related conditions. It works by stimulating a pathway involved in learning and memory, similar to other drugs used for neurodegenerative diseases.12345

Are You a Good Fit for This Trial?

This trial is for individuals with MELAS syndrome, a condition that affects many parts of the body, particularly the brain and nervous system. Participants must have genetic markers confirming their diagnosis. Specific details on who can't join are not provided here.

Inclusion Criteria

I have had stroke-like episodes confirmed by MRI.
Other criteria per the protocol
Signed consent form
See 5 more

Exclusion Criteria

I have not had bleeding disorders or unexplained bleeding in the last 6 months.
My cancer is not affecting the study's outcomes.
Systolic blood pressure (BP) 90 mmHg or diastolic BP 60 mmHg
See 6 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Treatment Period 1

Participants receive either zagociguat or placebo once daily for 12 weeks

12 weeks
3 visits (in-person), 2 visits (in-person or home)

Washout

A 4-week washout period between treatment periods

4 weeks

Treatment Period 2

Participants receive the alternate treatment (zagociguat or placebo) once daily for 12 weeks

12 weeks
3 visits (in-person), 2 visits (in-person or home)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

What Are the Treatments Tested in This Trial?

Interventions

  • Zagociguat
Trial Overview The study tests zagociguat at two different doses (15mg and 30mg) against a placebo to see which is more effective in treating MELAS symptoms. It's a double-blind study, meaning neither participants nor researchers know who gets the real drug or placebo during the trial.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Group I: Zagociguat 30mg then PlaceboExperimental Treatment2 Interventions
Participants first receive zagociguat 30 mg once a day for 12 weeks. Then after a 4-week washout, they receive placebo once a day for 12 weeks.
Group II: Zagociguat 15mg then PlaceboExperimental Treatment2 Interventions
Participants first receive zagociguat 15 mg once a day for 12 weeks. Then after a 4-week washout, they receive placebo once a day for 12 weeks.
Group III: Placebo then Zagociguat 30mgExperimental Treatment2 Interventions
Participants first receive placebo once a day for 12 weeks. Then after a 4-week washout, they receive zagociguat 30 mg once a day for 12 weeks.
Group IV: Placebo then Zagociguat 15mgExperimental Treatment2 Interventions
Participants first receive placebo once a day for 12 weeks. Then after a 4 week washout, they receive zagociguat 15 mg once a day for 12 weeks.

Zagociguat is already approved in United States for the following indications:

🇺🇸
Approved in United States as Zagociguat for:
  • Mitochondrial disease (Orphan Drug designation)

Find a Clinic Near You

Who Is Running the Clinical Trial?

Tisento Therapeutics

Lead Sponsor

Trials
6
Recruited
250+

Published Research Related to This Trial

Zagociguat, a stimulator of the nitric oxide-sGC-cGMP signaling pathway, was found to be well-tolerated in a phase 1b study involving 24 healthy participants aged 65 and older, with a notable ability to penetrate the blood-brain barrier.
While zagociguat caused modest reductions in blood pressure, no significant pharmacodynamic effects were observed, suggesting that further studies in individuals with cognitive impairment may be necessary to fully evaluate its potential benefits.
Randomized placebo-controlled crossover study to assess tolerability and pharmacodynamics of zagociguat, a soluble guanylyl cyclase stimulator, in healthy elderly.van Kraaij, SJW., Borghans, L., Klaassen, ES., et al.[2023]
In pivotal phase III trials, riociguat significantly improved the 6-minute walking distance (6MWD) in Chinese patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), with increases of +46 m in PATENT-1 and +102 m in CHEST-1.
Riociguat was well tolerated and also led to improvements in secondary endpoints such as pulmonary vascular resistance (PVR) and WHO functional class, indicating its efficacy and safety in this specific patient population.
Riociguat for the treatment of pulmonary hypertension: Chinese subgroup analyses and comparison.Wang, C., Jing, ZC., Huang, YG., et al.[2020]
Zagociguat (CY6463) is a novel stimulator of soluble guanylate cyclase (sGC) that was well-tolerated in healthy participants across various doses, indicating its safety for further development in treating neurodegenerative diseases.
The drug demonstrated central nervous system (CNS) penetration and induced significant reductions in blood pressure, but no consistent effects on neurocognitive function were observed, suggesting that while it may have cardiovascular effects, its impact on learning and memory needs further investigation.
First-in-human trial to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of zagociguat (CY6463), a CNS-penetrant soluble guanylyl cyclase stimulator.van Kraaij, SJW., Gal, P., Borghans, LGJM., et al.[2023]

Citations

Randomized placebo-controlled crossover study to assess tolerability and pharmacodynamics of zagociguat, a soluble guanylyl cyclase stimulator, in healthy elderly. [2023]
Riociguat for the treatment of pulmonary hypertension: Chinese subgroup analyses and comparison. [2020]
First-in-human trial to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of zagociguat (CY6463), a CNS-penetrant soluble guanylyl cyclase stimulator. [2023]
Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. [2020]
Riociguat for Sarcoidosis-Associated Pulmonary Hypertension: Results of a 1-Year Double-Blind, Placebo-Controlled Trial. [2023]
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