A Dose-ranging Study of TTI-0102 in Adults and Children With Leigh Syndrome Spectrum (LSS)

NCT06990984 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: TTI-LSS-001
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief 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. 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:

• 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

Outcome Measures

Primary Outcomes (6)

• PK: plasma cysteamine (Tmax)

  Measurement of cysteamine in plasma: Tmax

  Baseline (Day 1) to end of treatment (Day 84)

• PK: plasma cysteamine (Cmax)

  Measurement of cysteamine in plasma: Cmax

  Baseline (Day 1) to end of treatment (Day 84)

• PK: plasma cysteamine (Cmin)

  Measurement of cysteamine in plasma: Cmin

  Baseline (Day 1) to end of treatment (Day 84)

• PK: plasma cysteamine (PK curve)

  Measurement of cysteamine in plasma: PK curve

  Baseline (Day 1) to end of treatment (Day 84)

• PK: plasma cysteamine (AUC)

  Measurement of cysteamine in plasma: AUC

  Baseline (Day 1) to end of treatment (Day 84)

• PD: plasma glutathione

  Measurement of glutathione concentration in plasma

  Baseline (Day 1) to end of treatment (Day 84)

Secondary Outcomes (1)

• Safety and adverse events

  Baseline (Day 1) to final follow-up (Day 112)

Study Arms (2)

TTI-0102: cysteamine-pantetheine disulfide

EXPERIMENTAL

Drug: TTI-0102: cysteamine-pantetheine disulfide

Placebo

PLACEBO COMPARATOR

Drug: D-Mannitol

Interventions

TTI-0102: cysteamine-pantetheine disulfide DRUG

TTI-0102: cysteamine-pantetheine disulfide, powder for dissolution in water for oral administration

TTI-0102: cysteamine-pantetheine disulfide

D-Mannitol DRUG

D-Mannitol

Placebo

Eligibility Criteria

• Age: 5 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Thiogenesis Therapeutics, Inc.: lead

MeSH Terms

Conditions

Leigh Disease

Interventions

cysteamine-pantetheine disulfide; Mannitol

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pyruvate Metabolism, Inborn Errors; Carbohydrate Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Mitochondrial Diseases

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

Study Officials

• Zarazuela Zolkipli-Cunningham, MBChB, MRCP

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

• Patrice Rioux, MD, PhD

  Thiogenesis Therapeutics

  STUDY DIRECTOR

Central Study Contacts

TTI-LSS-001 Recruitment

CONTACT

+1 (858) 500-6621; clinreg@thiogenesis.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All parties will be blinded during the placebo-controlled Sequence 1
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: partially randomized, placebo-controlled, sequential dose-ranging treatment study

Study Record Dates

• First Submitted: May 6, 2025
• First Posted: May 25, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: July 11, 2025

Record last verified: 2025-07