Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome)Phase 2NCT06961344
An Open-label Extension Safety Study of MELAS Patients Who Completed TIS6463-203 (PRIZM)
A Phase 2 study testing zagociguat 15mg in people with Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome), run by Tisento Therapeutics at 16 sites in 5 countries.
Trial summary
The goal of this clinical trial is to evaluate the long-term safety and tolerability of zagociguat in patients with MELAS who completed study medication treatment in the lead-in study TIS6463-203. TIS6463-204 is evaluating zagociguat in an open-label extension study at the daily dose of 15mg. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome)
- What is being tested?
- zagociguat 15mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 16 sitesin 5 countries
- Study dates
- 18 Aug 2025to 29 Oct 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form (ICF).
- Completed TIS6463-203 treatment through the Period 2 Week 12 Visit.
- Agrees to follow lifestyle restrictions.
- Other criteria per the protocol.
Who cannot join
- 1. Any medical condition or clinical finding that, per investigator judgement, would preclude safe study participation and/or completion of all trial requirements.
Trial locations and contacts
16 sites in 5 countries.
16 sites in 5 countries
United States9 sites
Akron Children's Hospital
Akron, Ohio, 44308
Rare Disease Research
Atlanta, Georgia, 30329
Children's Hospital of Colorado
Aurora, Colorado, 80045
Massachusetts General Hospital
Boston, Massachusetts, 02114
Baylor College of Medicine
Houston, Texas, 77030
UT Health Houston
Houston, Texas, 77030
UC San Diego - Altman Clinical and Translational Research Institute
La Jolla, California, 92037
Mount Sinai - Ichan School of Medicine
New York, New York, 10029
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Australia2 sites
Royal Melbourne Hospital
Melbourne, Victoria, 3052
Neuroscience Research Australia
Sydney, New South Wales, NSW 2031
Italy2 sites
Neurologic Institute Carlo Besta of Milan
Milan, 20133
Fondazione Policlinico Universitario Agostino Gemelli
Rome, 00168
United Kingdom2 sites
University College London Hospital. The National Hospital for Neurology and Neurosurgery, Centre for Neuromuscular Diseases
London, WC1N 3BG
The Newcastle upon Tyne NHS Foundation Trust
Newcastle upon Tyne, NE14LP
Germany1 site
LMU Klinikum, Friedrich-Baur-Institute, Department of Neurology
Munich, 80336
About this study
Official title: An Open-label Extension Study Evaluating the Safety of Zagociguat in Participants With MELAS Who Completed TIS6463-203
The goal of this clinical trial is to evaluate the long-term safety and tolerability of zagociguat in patients with MELAS who completed study medication treatment in the lead-in study TIS6463-203. TIS6463-204 is evaluating zagociguat in an open-label extension study at the daily dose of 15mg. The study medication is a once daily oral table and will be provided at the clinic and/or shipped to the participant's home. Study assessments will be conducted during clinic visits which will occur at three months and then at six months. Thereafter, clinic visits will occur every six months.
Read the detailed description
On Screening Visit Day -1 (which corresponds to Period 2 Week 12 Visit from lead-in study TIS6463-203), participants will sign the informed consent form, be confirmed eligible for this open-label extension study and undergo Screening Visit assessments. Eligible participants will begin dosing the next day on Day 1 (there is no Day 0) at home. Participants will have a 3-month visit and 6-month study visit at the clinic and thereafter will have a clinic visit every 6 months. Participants should have a Follow-up Visit 4 (+1) weeks after zagociguat discontinuation.
- Being tested
- zagociguat 15mg
- Keywords
- MELAS
- Medical subject headings
- Mitochondrial encephalopathy, Acidosis, Lactic, MELAS Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zagociguat 15mgDrug
Also called IW-6463, CY6463
once daily oral tablets
| Study group | Role | What they receive |
|---|---|---|
| Zagociguat 15mg | Experimental | Participants receive zagociguat 15 mg once a day (QD) for the duration of the study. Receives: Drug: zagociguat 15mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-emergent Adverse Events (TEAEs)
TEAEs are any untoward event that may or may not be related to study medication.
Measured: Day 1 through the Follow-up for treatment period 4 weeks after last dose of study medication.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2025
- Study start18 Aug 2025
- Primary completion29 Oct 2026
- Study completion29 Oct 2026
Why it stopped: Terminated based on results from the parent study, which did not meet its primary or secondary efficacy endpoints. The decision was not related to a safety.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- An open-label, single-group assignment extension study. Eligible patients will be entered into a single treatment sequence. The treatment period will last for the shortest of the following: 104 weeks; regulatory approval and commercial availability of zagociguat in the participant's respective country; or termination of the clinical development of zagociguat in MELAS
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tisento Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06961344
- Sponsor's protocol ID
- TIS6463-204
- Status last verified
- Nov 2026
- First submitted
- 28 Apr 2025
- Last updated
- 6 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Extension Study Evaluating the Safety of Zagociguat in Participants With MELAS Who Completed TIS6463-203
- ClinicalTrials.gov ID
- NCT06961344
- Acronym / sponsor ID
- TIS6463-204
- Keywords
- MELAS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated based on results from the parent study, which did not meet its primary or secondary efficacy endpoints. The decision was not related to a safety.
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Tisento TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 18 Aug 2025 (actual)
- Primary completion
- 29 Oct 2026 (actual)
- Study completion
- 29 Oct 2026 (actual)
- First posted
- 7 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to evaluate the long-term safety and tolerability of zagociguat in patients with MELAS who completed study medication treatment in the lead-in study TIS6463-203. TIS6463-204 is evaluating zagociguat in an open-label extension study at the daily dose of 15mg. The study medication is a once daily oral table and will be provided at the clinic and/or shipped to the participant's home. Study assessments will be conducted during clinic visits which will occur at three months and then at six months. Thereafter, clinic visits will occur every six months.
Detailed description
On Screening Visit Day -1 (which corresponds to Period 2 Week 12 Visit from lead-in study TIS6463-203), participants will sign the informed consent form, be confirmed eligible for this open-label extension study and undergo Screening Visit assessments. Eligible participants will begin dosing the next day on Day 1 (there is no Day 0) at home. Participants will have a 3-month visit and 6-month study visit at the clinic and thereafter will have a clinic visit every 6 months. Participants should have a Follow-up Visit 4 (+1) weeks after zagociguat discontinuation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- An open-label, single-group assignment extension study. Eligible patients will be entered into a single treatment sequence. The treatment period will last for the shortest of the following: 104 weeks; regulatory approval and commercial availability of zagociguat in the participant's respective country; or termination of the clinical development of zagociguat in MELAS
| Arm | Type | Receives |
|---|---|---|
| Zagociguat 15mg | Experimental | Drug: zagociguat 15mgParticipants receive zagociguat 15 mg once a day (QD) for the duration of the study. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form (ICF).
- Completed TIS6463-203 treatment through the Period 2 Week 12 Visit.
- Agrees to follow lifestyle restrictions.
- Other criteria per the protocol.
Key exclusion criteria (1 listed)
- 1. Any medical condition or clinical finding that, per investigator judgement, would preclude safe study participation and/or completion of all trial requirements.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| zagociguat 15mgAlso: IW-6463, CY6463once daily oral tablets | Drug | Zagociguat 15mg |
Primary outcome
Incidence of Treatment-emergent Adverse Events (TEAEs)
Time frame: Day 1 through the Follow-up for treatment period 4 weeks after last dose of study medication.
TEAEs are any untoward event that may or may not be related to study medication.
Results and safety
The study was stopped early (reason given: Terminated based on results from the parent study, which did not meet its primary or secondary efficacy endpoints. The decision was not related to a safety.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
- Individual participant dataSharing planned: No
Related trials for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome)
Not yet recruitingPhase 1/2
A Basket Clinical Study to Assess Glycerol Tributyrate in Patients With Mitochondrial Encephalopathy, Lactic Acidosis, Stroke-like Episodes (MELAS) or Leber's Hereditary Optic Neuropathy-Plus (LHON-Plus)
MELAS Syndrome, Lebers Hereditory Optic Neuropathy With Extra Ocular Symptoms (LHON-Plus)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
16 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing zagociguat 15mg in people with Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome), run by Tisento Therapeutics at 16 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, Australia, Italy, United Kingdom, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Terminated based on results from the parent study, which did not meet its primary or secondary efficacy endpoints. The decision was not related to a safety.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-emergent Adverse Events (TEAEs) (time frame: Day 1 through the Follow-up for treatment period 4 weeks after last dose of study medication.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.