Leigh SyndromePhase 2NCT06990984
A Dose-ranging Study of TTI-0102 in Adults and Children With Leigh Syndrome Spectrum (LSS)
A Phase 2 study testing TTI-0102: cysteamine-pantetheine disulfide and D-Mannitol in people with Leigh Syndrome, run by Thiogenesis Therapeutics, Inc..
Trial summary
The goal of this clinical trial is to investigate oral TTI-0102 to evaluate its pharmacokinetics, safety, and preliminary efficacy in patients with Leigh syndrome spectrum, in three sequences. First sequence will be placebo-controlled and include 12 adolescents and adults weighing more than 40 kg. Read more about this study
- Who is it for?
- Ages 5 to 55 years
- Conditions the study is for
- Leigh Syndrome
- What is being tested?
- TTI-0102: cysteamine-pantetheine disulfide and D-Mannitol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- No sites listed yet
- Study dates
- Oct 2026to Sep 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 5 to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Individuals aged 5 years to 55 years (inclusive) and weight-eligible, at the time of informed consent / assent and enrollment
- Confirmed diagnosis of Leigh syndrome or Leigh-like disorder (Leigh syndrome spectrum [LSS]) with neurodevelopmental manifestations, which include documented developmental delay, developmental regression, or abnormal neurologic exam findings
- Willing and able to comply with required study schedule and procedures, including daily TTI-0102 study drug dosing requirements, i.e., able to ingest solution orally
- Adequate liver function as evidenced by total bilirubin < 1.5x upper limit of normal (ULN) and liver function tests < 3x ULN
- Normal hematologic parameters defined as:
- Absolute neutrophil count ≥ 1.0 x 109/L Platelet count ≥ 100,000/mm3 (100 x 109/L) Hemoglobin ≥ 9 g/dL
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- Non-fasting serum triglycerides < 300 mg/dL and non-fasting serum cholesterol < 300 mg/dL
- Serum amylase and lipase < 2x ULN
- Adequate immunoglobulin levels as outlined below that, in the opinion of the investigator, will not place the patient at increased risk of infection:
- IgG ≥ 200 mg/dL IgM ≥ 30 mg/dL IgA ≥ 10 mg/dL
- All sexually-active participants must agree to use effective contraception during study participation:
- Females of reproductive potential must agree to use effective contraception without interruption from 28 days prior to starting TTI-0102 through 30 days after last dose of TTI-0102; have a negative serum pregnancy test result at screening; and agree to ongoing urine pregnancy testing during the subsequent study period.
- Male patients must practice abstinence or agree to use a condom during sexual contact with a pregnant female or a female of reproductive potential while participating in the study and through 30 days after the last dose of TTI-0102
Who cannot join
- Documented diagnosis of concurrent inborn errors of metabolism
- Non-elective hospitalization related to their Leigh syndrome or mitochondrial disease within 60 days prior to screening
- Treatment with taurine during the previous 30 days of screening, and not willing to discontinue for the duration of the study
- Severe gastrointestinal disease including gastroparesis
- Presence or having sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs
- In the opinion of the investigator, clinically-significant or severe cardiac conditions, at the time of screening
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- History of drug or alcohol abuse
- History of pancreatitis
- Known or suspected hypersensitivity to cysteamine
- Allergy to any medicine containing mercaptamine, penicillamine, or known hypersensitivity to any of the study drug ingredients
- Exposure to any live vaccinations within 30 days prior to the first dose of TTI-0102, except for the influenza and / or COVID-19 vaccines
- Planned surgical procedure during the study period
- Clinically-significant proteinuria that requires ongoing medical therapy
- Patients who are breastfeeding and / or are pregnant
- History of solid organ transplant or bone marrow transplant
- Treatment with any investigational drug, including an investigational drug for mitochondrial disease, within 30 days prior to receiving the first dose of TTI-0102
- Patients with confirmed or suspected increased intracranial pressure, pseudotumor cerebri / idiopathic intracranial hypertension, and or papilledema
- Currently active malignancy (other than adequately treated non-melanoma skin cancers, carcinoma in situ of the cervix, or other adequately treated carcinoma in situ) and / or ongoing treatment for malignancy are ineligible. Patients are not considered to have a currently active malignancy if they have completed therapy and are free of disease for at least one year
- Recent infection requiring systemic anti-infective treatment that was completed ≤ 14 days prior to screening
- Uncontrolled diabetes mellitus, as defined by HbA1c > 8%, despite adequate therapy
- History of interstitial lung disease and / or pneumonitis
- Known human immunodeficiency virus, active hepatitis B and / or hepatitis C infection(s)
- Any uncontrolled psychiatric or medical condition which, in the opinion of the investigator, would interfere with the patient's safe participation in the study
- Any other condition or prior therapy that in the opinion of the investigator would render the participant unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol and / or likelihood of non-compliance with any study requirements
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Phase 2a Partially Randomized, Placebo-controlled, Sequential Dose-ranging Study of TTI-0102 in Adults and Children With Leigh Syndrome Spectrum
The goal of this clinical trial is to investigate oral TTI-0102 to evaluate its pharmacokinetics, safety, and preliminary efficacy in patients with Leigh syndrome spectrum, in three sequences. First sequence will be placebo-controlled and include 12 adolescents and adults weighing more than 40 kg. Second sequence will be open-label and include 3 adults and 3 children weighing 25-40 kg. Third sequence will also be open-label and will include 3 children weighing 20-25 kg. The main questions clinical trial aims to answer are:
- Characterize the relationship between TTI-0102 drug levels by measuring
Read more
- cysteamine pharmacokinetic (PK) parameters
- pharmacodynamic (PD) efficacy measures
- Generate a population PK model and determine dose level for later dosing groups
- collect data to inform the design of a subsequent phase 2b/3 study of TTI-0102 in this patient population
Participants will be asked to:
- Take the study drug twice daily for 12 weeks
- Visit the clinic for checkups and testing 7 times in total: once prior to study drug dosing, then 5 times over the 12-week treatment period and one more time a month after the last study drug dose.
- Conditions
- Leigh Syndrome
- Being tested
- TTI-0102: cysteamine-pantetheine disulfide, D-Mannitol
- Medical subject headings
- Leigh Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TTI-0102: cysteamine-pantetheine disulfideDrug
TTI-0102: cysteamine-pantetheine disulfide, powder for dissolution in water for oral administration
D-MannitolDrug
D-Mannitol
| Study group | Role | What they receive |
|---|---|---|
| TTI-0102: cysteamine-pantetheine disulfide | Experimental | Not described Receives: Drug: TTI-0102: cysteamine-pantetheine disulfide |
| Placebo | Placebo comparator | Not described Receives: Drug: D-Mannitol |
What is being measured
The primary outcome is the main question the study is designed to answer.
PK: plasma cysteamine (Tmax)
Measurement of cysteamine in plasma: Tmax
Measured: Baseline (Day 1) to end of treatment (Day 84)
PK: plasma cysteamine (Cmax)
Measurement of cysteamine in plasma: Cmax
Measured: Baseline (Day 1) to end of treatment (Day 84)
PK: plasma cysteamine (Cmin)
Measurement of cysteamine in plasma: Cmin
Measured: Baseline (Day 1) to end of treatment (Day 84)
PK: plasma cysteamine (PK curve)
Measurement of cysteamine in plasma: PK curve
Measured: Baseline (Day 1) to end of treatment (Day 84)
PK: plasma cysteamine (AUC)
Measurement of cysteamine in plasma: AUC
Measured: Baseline (Day 1) to end of treatment (Day 84)
PD: plasma glutathione
Measurement of glutathione concentration in plasma
Measured: Baseline (Day 1) to end of treatment (Day 84)
Secondary outcomes (1)
Safety and adverse events
Number of participants with treatment-emergent adverse events [comparing active vs. placebo]
Measured: Baseline (Day 1) to final follow-up (Day 112)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2025
- Study startOct 2026 (estimated)
- Primary completionJun 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leigh SyndromeStudies 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
- Randomised
- Intervention model
- Sequential
- Model description
- partially randomized, placebo-controlled, sequential dose-ranging treatment study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Thiogenesis Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Zarazuela Zolkipli-Cunningham, MBChB, MRCP, Principal investigator, Children's Hospital of PhiladelphiaPatrice Rioux, MD, PhD, Study director, Thiogenesis Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06990984
- Sponsor's protocol ID
- TTI-LSS-001
- Status last verified
- Jul 2026
- First submitted
- 6 May 2025
- Last updated
- 24 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: This is an exploratory study and we are not certain yet what data will be shared with other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a Partially Randomized, Placebo-controlled, Sequential Dose-ranging Study of TTI-0102 in Adults and Children With Leigh Syndrome Spectrum
- ClinicalTrials.gov ID
- NCT06990984
- Acronym / sponsor ID
- TTI-LSS-001
- Conditions
- Leigh Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Thiogenesis Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2026 (estimated)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 25 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 investigate oral TTI-0102 to evaluate its pharmacokinetics, safety, and preliminary efficacy in patients with Leigh syndrome spectrum, in three sequences. First sequence will be placebo-controlled and include 12 adolescents and adults weighing more than 40 kg. Second sequence will be open-label and include 3 adults and 3 children weighing 25-40 kg. Third sequence will also be open-label and will include 3 children weighing 20-25 kg. The main questions clinical trial aims to answer are:
- Characterize the relationship between TTI-0102 drug levels by measuring
- cysteamine pharmacokinetic (PK) parameters
- pharmacodynamic (PD) efficacy measures
- Generate a population PK model and determine dose level for later dosing groups
- collect data to inform the design of a subsequent phase 2b/3 study of TTI-0102 in this patient population
Participants will be asked to:
- Take the study drug twice daily for 12 weeks
- Visit the clinic for checkups and testing 7 times in total: once prior to study drug dosing, then 5 times over the 12-week treatment period and one more time a month after the last study drug dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- partially randomized, placebo-controlled, sequential dose-ranging treatment study
| Arm | Type | Receives |
|---|---|---|
| TTI-0102: cysteamine-pantetheine disulfide | Experimental | Drug: TTI-0102: cysteamine-pantetheine disulfide |
| Placebo | Placebo comparator | Drug: D-Mannitol |
Who may qualify
- Ages
- 5 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- Individuals aged 5 years to 55 years (inclusive) and weight-eligible, at the time of informed consent / assent and enrollment
- Confirmed diagnosis of Leigh syndrome or Leigh-like disorder (Leigh syndrome spectrum [LSS]) with neurodevelopmental manifestations, which include documented developmental delay, developmental regression, or abnormal neurologic exam findings
- Willing and able to comply with required study schedule and procedures, including daily TTI-0102 study drug dosing requirements, i.e., able to ingest solution orally
- Adequate liver function as evidenced by total bilirubin < 1.5x upper limit of normal (ULN) and liver function tests < 3x ULN
- Normal hematologic parameters defined as:
Key exclusion criteria (24 listed)
- Documented diagnosis of concurrent inborn errors of metabolism
- Non-elective hospitalization related to their Leigh syndrome or mitochondrial disease within 60 days prior to screening
- Treatment with taurine during the previous 30 days of screening, and not willing to discontinue for the duration of the study
- Severe gastrointestinal disease including gastroparesis
- Presence or having sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs
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 |
|---|---|---|
| TTI-0102: cysteamine-pantetheine disulfideTTI-0102: cysteamine-pantetheine disulfide, powder for dissolution in water for oral administration | Drug | TTI-0102: cysteamine-pantetheine disulfide |
| D-MannitolD-Mannitol | Drug | Placebo |
Primary outcome
PK: plasma cysteamine (Tmax)
Time frame: Baseline (Day 1) to end of treatment (Day 84)
Measurement of cysteamine in plasma: Tmax
PK: plasma cysteamine (Cmax)
Time frame: Baseline (Day 1) to end of treatment (Day 84)
Measurement of cysteamine in plasma: Cmax
PK: plasma cysteamine (Cmin)
Time frame: Baseline (Day 1) to end of treatment (Day 84)
Measurement of cysteamine in plasma: Cmin
PK: plasma cysteamine (PK curve)
Time frame: Baseline (Day 1) to end of treatment (Day 84)
Measurement of cysteamine in plasma: PK curve
PK: plasma cysteamine (AUC)
Time frame: Baseline (Day 1) to end of treatment (Day 84)
Measurement of cysteamine in plasma: AUC
PD: plasma glutathione
Time frame: Baseline (Day 1) to end of treatment (Day 84)
Measurement of glutathione concentration in plasma
1 secondary outcome
Safety and adverse events
Time frame: Baseline (Day 1) to final follow-up (Day 112)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2026.
- Individual participant dataSharing planned: Undecided. This is an exploratory study and we are not certain yet what data will be shared with other researchers.
Related trials for Leigh Syndrome
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Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
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Global Registry and Natural History Study for Mitochondrial Disorders
Mitochondrial Diseases, Kearns-Sayre Syndrome
Enrolling by invitationPhase 2
Sirolimus for Leigh Syndrome
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North American Mitochondrial Disease Consortium Patient Registry and Biorepository (NAMDC)
Mitochondrial Disorders, Mitochondrial Genetic Disorders
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.
Zarazuela Zolkipli-Cunningham, MBChB, MRCP principal investigator
Children's Hospital of Philadelphia
Patrice Rioux, MD, PhD study director
Thiogenesis Therapeutics
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TTI-0102: cysteamine-pantetheine disulfide and D-Mannitol in people with Leigh Syndrome, run by Thiogenesis Therapeutics, Inc..
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 13 inclusion and 24 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: opening soon, as of the sponsor's last update on 24 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact TTI-LSS-001 Recruitment (+1 (858) 500-6621, clinreg@thiogenesis.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PK: plasma cysteamine (Tmax) (time frame: Baseline (Day 1) to end of treatment (Day 84)). The study lists 6 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 24 Jul 2026.