MELASPhase 2NCT04475549
Phase 2a Study of IW-6463 in Adults Diagnosed With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)
A Phase 2 study testing IW-6463 Tablets in people with MELAS, run by Tisento Therapeutics at 5 sites in United States.
Trial summary
This is a single-arm study to evaluate safety and tolerability of oral IW-6463 in adults diagnosed with MELAS. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- MELAS
- What is being tested?
- IW-6463 Tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 5 sitesUnited States
- Study dates
- 13 Nov 2020to 23 Jan 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Prior genetic confirmation of a known mitochondrial disease mutation
- Neurological features of MELAS (can be based on medical history)
- Elevated plasma lactate levels at Screening Visit (≥1.0 mmol/L)
- Women of childbearing potential must have a negative pregnancy test prior to randomization and must agree to use protocol-specified contraception from the Screening Visit through 90 days after the final dose of study drug.
- Male participants must be surgically sterile by vasectomy (conducted ≥60 days before the Screening Visit or confirmed via sperm analysis) or must agree to use protocol-specified contraception and agree to refrain from sperm donation from the Screening Visit through 90 days after the final dose of study drug.
- Other inclusion criteria per protocol
Who cannot join
- Positive pregnancy test at Screening or on Day 1
- Hypotension defined as systolic blood pressure (BP) ≤90 mmHg or diastolic BP ≤60 mmHg at Screening or predose at Day 1
- Hypertension defined as systolic BP >160 mmHg or diastolic BP >100 mmHg, at Screening or predose at Day 1
- Uncontrolled diabetes
- Severe gastrointestinal dysmotility as determined by the investigator that may impact compliance and/or oral drug administration, absorption and exposure.
- Unable to fast for 3-4 hours after a meal
Show all 10Show fewer
- Unable or unwilling to adhere to the study schedule, lifestyle restrictions, assessment requirements or, in the clinical judgment of the investigator, is otherwise not suitable for study participation.
- Current or past history of clinically significant cardiomyopathy and/or cardiac conduction abnormality
- Used any nicotine-containing products (eg, cigarettes, e-cigarettes, vape pens, cigars) within 1 month of enrollment
- Other exclusion criteria per protocol
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Johns Hopkins University
Baltimore, Maryland, 21205
Massachusetts General Hospital
Boston, Massachusetts, 02114
Columbia University
New York, New York, 10032
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's National Hospital of DC
Washington D.C., District of Columbia, 20010
About this study
Official title: A Phase 2a Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Individuals With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)
This is a single-arm study to evaluate safety and tolerability of oral IW-6463 in adults diagnosed with MELAS.
Read the detailed description
IW-6463 tablets will be orally administered once-daily (QD) for up to 29 days
- Conditions
- MELAS
- Being tested
- IW-6463 Tablets
- Keywords
- mitochondrial disease
- Medical subject headings
- MELAS Syndrome, Mitochondrial Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IW-6463 TabletsDrug
Also called CY6463, zagociguat
IW-6463 tablets administered orally (daily)
| Study group | Role | What they receive |
|---|---|---|
| IW-6463 | Experimental | Open-label IW-6463 15 mg once daily (QD), with possibility to dose reduce to 10 mg. Receives: Drug: IW-6463 Tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Study Drug Dose Reductions or Discontinuations Due to ≥ 1 Treatment Emergent Adverse Event (TEAE)
A TEAE is defined as an adverse event (AE) with an onset that occurs between the first dose of study drug and the end of study period. AEs are defined as an untoward medical occurrence that does not necessarily have a causal relationship with study drug treatment.
Measured: From first dose date to Day 43 (±4)
Number of Participants Who Experienced ≥1 AE, TEAE, Serious AE (SAE), or TEAE of Special Interest (AESI)
AEs are defined as an untoward medical occurrence that does not necessarily have a causal relationship with study drug treatment. A TEAE is defined as an AE with an onset that occurs from the first dose of study drug up until the end of study period. An SAE is an AE that fulfills 1 or more of the following: results in death; is immediately life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; is an important medical event that may jeopardize the participant or may require medical intervention to prevent 1 of the outcomes listed above. Events were categorized as mild, moderate, or severe and as related or unrelated to study drug. AESIs include bleeding events, symptomatic hypotensive events and/or tachycardia, dizziness, syncope, and TEAEs related to change of neurobehaviors (ie, suicidality or euphoria).
Measured: From first dose date to Day 43 (±4)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2020
- Study start13 Nov 2020
- Primary completion23 Jan 2022
- Study completion23 Jan 2022
Why it stopped: Study terminated due to enrollment challenges.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MELASStudies 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
- Open-label, single-arm study with daily dosing for up to 29 days.
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tisento Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chad Glasser, PharmD, Study director, Cyclerion Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04475549
- Sponsor's protocol ID
- C6463-201
- Status last verified
- Aug 2024
- First submitted
- 14 Jul 2020
- Last updated
- 29 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- 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 29 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Individuals With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)
- ClinicalTrials.gov ID
- NCT04475549
- Acronym / sponsor ID
- C6463-201
- Conditions
- MELAS
- Keywords
- mitochondrial disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated due to enrollment challenges.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Tisento TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 13 Nov 2020 (actual)
- Primary completion
- 23 Jan 2022 (actual)
- Study completion
- 23 Jan 2022 (actual)
- First posted
- 17 Jul 2020 (actual)
- Results
- Posted 15 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-arm study to evaluate safety and tolerability of oral IW-6463 in adults diagnosed with MELAS.
Detailed description
IW-6463 tablets will be orally administered once-daily (QD) for up to 29 days
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label, single-arm study with daily dosing for up to 29 days.
| Arm | Type | Receives |
|---|---|---|
| IW-6463 | Experimental | Drug: IW-6463 TabletsOpen-label IW-6463 15 mg once daily (QD), with possibility to dose reduce to 10 mg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Prior genetic confirmation of a known mitochondrial disease mutation
- Neurological features of MELAS (can be based on medical history)
- Elevated plasma lactate levels at Screening Visit (≥1.0 mmol/L)
- Women of childbearing potential must have a negative pregnancy test prior to randomization and must agree to use protocol-specified contraception from the Screening Visit through 90 days after the final dose of study drug.
- Male participants must be surgically sterile by vasectomy (conducted ≥60 days before the Screening Visit or confirmed via sperm analysis) or must agree to use protocol-specified contraception and agree to refrain from sperm donation from the Screening Visit through 90 days after the final dose of study drug.
Key exclusion criteria (10 listed)
- Positive pregnancy test at Screening or on Day 1
- Hypotension defined as systolic blood pressure (BP) ≤90 mmHg or diastolic BP ≤60 mmHg at Screening or predose at Day 1
- Hypertension defined as systolic BP >160 mmHg or diastolic BP >100 mmHg, at Screening or predose at Day 1
- Uncontrolled diabetes
- Severe gastrointestinal dysmotility as determined by the investigator that may impact compliance and/or oral drug administration, absorption and exposure.
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 |
|---|---|---|
| IW-6463 TabletsAlso: CY6463, zagociguatIW-6463 tablets administered orally (daily) | Drug | IW-6463 |
Primary outcome
Number of Participants With Study Drug Dose Reductions or Discontinuations Due to ≥ 1 Treatment Emergent Adverse Event (TEAE)
Time frame: From first dose date to Day 43 (±4)
A TEAE is defined as an adverse event (AE) with an onset that occurs between the first dose of study drug and the end of study period. AEs are defined as an untoward medical occurrence that does not necessarily have a causal relationship with study drug treatment.
Number of Participants Who Experienced ≥1 AE, TEAE, Serious AE (SAE), or TEAE of Special Interest (AESI)
Time frame: From first dose date to Day 43 (±4)
AEs are defined as an untoward medical occurrence that does not necessarily have a causal relationship with study drug treatment. A TEAE is defined as an AE with an onset that occurs from the first dose of study drug up until the end of study period. An SAE is an AE that fulfills 1 or more of the following: results in death; is immediately life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; is an important medical event that may jeopardize the participant or may require medical intervention to prevent 1 of the outcomes listed above. Events were categorized as mild, moderate, or severe and as related or unrelated to study drug. AESIs include bleeding events, symptomatic hypotensive events and/or tachycardia, dizziness, syncope, and TEAEs related to change of neurobehaviors (ie, suicidality or euphoria).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Chad Glasser, PharmD study director
Cyclerion Therapeutics, Inc.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IW-6463 Tablets in people with MELAS, run by Tisento Therapeutics at 5 sites in United States.
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 6 inclusion and 10 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 29 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. 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?
Yes. Results are posted in the registry (first posted 15 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Study Drug Dose Reductions or Discontinuations Due to ≥ 1 Treatment Emergent Adverse Event (TEAE) (time frame: From first dose date to Day 43 (±4)). The study lists 2 primary outcomes in all. 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 29 Aug 2024.