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A Phase 2b Study of Zagociguat in Patients with MELAS

PHASE2RECRUITING

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.

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Study details:

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 are:. * Does zagociguat improve fatigue in patients with MELAS?.

* Does zagociguat improve cognitive performance in patients with MELAS?. * What is the safety and tolerability profile of zagociguat?. The PRIZM study is evaluating 2 dose levels of zagociguat in a crossover design consisting of two 12-week treatment periods separated by a 4-week washout.

Patients will be screened and if eligible, randomly assigned either to receive placebo in period 1 followed by active drug in period 2 OR to receive active drug in period 1 followed by placebo in period 2. Study medication is a once daily oral tablet and will be provided at the clinic and/or shipped to the participant's home. Clinic visits will occur at screening and Week 1 and Week 12 of each treatment period.

Visits at Week 4 and Week 8 of both crossover periods will either be in clinic or optionally at the participant's home. Study assessments will be conducted weekly on a phone app and a separate tablet and additional assessments will be conducted during visits. Patients who complete the study will be eligible for an open label extension study.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

Signed consent form.

18 to 75 years of age.

Diagnosed with MELAS based on the presence of each of the following criteria: A documented pathogenic variant in a mitochondrial DNA (mtDNA) gene. History of one or more stroke-like episodes (SLEs) with magnetic resonance imaging (MRI) findings consistent with stroke-like lesions.

Scores below normal average on composite memory score from One Back and One Card Learning tests.

Reports fatigue due to MELAS.

Can complete at least 1 sit-to-stand in the 30-second test interval.

Completes all at-home weekly activities independently during the Screening Period (caregiver may help set up device/app, log-in, etc.).

Other criteria per the protocol.

Exclusion criteria

Systolic blood pressure (BP) 90 mmHg or diastolic BP 60 mmHg.

Orthostatic hypotension when measured after standing from a semi-recumbent/supine position.

Active cancer significant enough to confound the results of this study.

Severe gastrointestinal dysmotility that may impact participation.

Recent history (within last 6 months) of platelet dysfunction, hemophilia, von Willebrand disease, coagulation disorder, other bleeding diathesis condition(s), or significant, nontraumatic bleeding episodes.

History of spontaneous fracture(s) that in the investigator's opinion represents a safety risk for trial participation.

Current use of prohibited medication (reviewed by investigator).

Any medical or other condition that the investigator thinks would preclude study participation.

Other exclusion criteria per protocol.

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2024-09-10

Primary completion: 2025-09-01

Study completion finish: 2025-09-01

Study type

TREATMENT

Phase

PHASE2

Trial ID

NCT06402123

Intervention or treatment

DRUG: zagociguat 15mg

DRUG: zagociguat 30mg

DRUG: Placebo

Conditions

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

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

Condition: Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome)
DRUG: zagociguat 15mg and other drugs
Melbourne, Victoria, Australia and more
Sponsor: Tisento Therapeutics

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

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Find a site

Closest Location:

Royal Melbourne Hospital

Research sites nearby

Select from list below to view details:

Royal Melbourne Hospital
Melbourne, Victoria, Australia
Neuroscience Research Australia
Sydney, New South Wales, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Placebo then Zagociguat 15mg 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.	DRUG: zagociguat 15mg Once-daily oral tablets
EXPERIMENTAL: Zagociguat 15mg then Placebo 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.	DRUG: zagociguat 15mg Once-daily oral tablets
EXPERIMENTAL: Placebo then Zagociguat 30mg 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.	DRUG: zagociguat 30mg Once-daily oral tablets
EXPERIMENTAL: Zagociguat 30mg then Placebo 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.	DRUG: zagociguat 30mg Once-daily oral tablets

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
• PROMIS Fatigue MELAS Short Form scores • Memory composite scores (One Card Learning and One Back Tests) • International Digit Symbol Substitution Test scores	These measures are a patient reported questionnaire on MELAS-specific fatigue and 3 cognitive performance tests. These 3 outcome measures will be combined using a global statistical test.	Weeks 9 through 12 of each treatment period
Incidence of Treatment-emergend Adverse Events (TEAEs)	TEAEs are any untoward event that may or may not be related to study medication.	Weeks 1 through washout for treatment period 1 and Weeks 1 through follow-up for treatment period 2

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Number of repetitions completed during the 30-second sit-to-stand test	Leg strength and exercise intolerance	Week 12
Groton Maze Learning Test (GMLT) scores	Test of executive function	Week 9 through 12
PROMIS Cognitive Function MELAS Short Form (PCFM-SF) score	Patient-reported questionnaire on MELAS-specific cognitive function	Week 12
Plasma concentrations of GDF-15	Measure of disease pathophysiology	Week 12

Frequently Asked Questions

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You may be eligible to participate in this trial based on your search.Apply for study

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References

Clinical Trials Gov: A Phase 2b Study of Zagociguat in Patients with MELAS