A Study to Assess TTI-0102 vs Placebo in MELAS Patients

NCT06644534 | Recruiting Phase 2

• 1 other identifier: TTI-MITO-001
• Study Type: interventional
• Target: 12
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a randomized, double-blind, placebo-controlled study. Prior to treatment, patients will undergo a screening visit. If eligible, each subject will return for a Day 1 visit and will receive their first dose of investigational product (TTI-0102 or placebo). At the end of the first week of treatment, subjects will return for a Week 1/Day 8 study visit to assess study drug dosing/tolerance and instruct on dosing for the upcoming second week of treatment. For the first 8 weeks of treatment, subjects will alternate between returning to the clinic for detailed assessments (Weeks 4 and 8) and receiving a telephone call from the Investigator team to assess safety and TTI-0102 dose (Weeks 2 and 6) and the potential need for an immediate unscheduled study visit. After the first 8 weeks of treatment, subjects will continue to return to the clinic for monthly assessments at Weeks 12, 16, 20. The Study Exit visit will occur at Week 24, and subjects will be offered to continue on an open-label extension study of TTI-0102. If a subject does not complete the study, they will be asked to return for a Study Exit visit 4 weeks after last study drug dose. Primary Objective The primary objective of this study is to assess the efficacy, safety and tolerability of oral TTI 0102 compared to placebo, for up to 6 months in patients with MELAS. Secondary Objective The secondary objectives of this study are to assess the efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of cysteamine after oral administration of TTI-0102 at steady state, in patients with MELAS on a stable dose of TTI-0102. This is a randomized, double-blind, placebo-controlled study. Prior to treatment, patients will undergo a screening visit. If eligible, each subject will return for a Day 1 visit and will receive their first dose of investigational product (TTI-0102 or placebo). At the end of the first week of treatment, subjects will return for a Week 1/Day 8 study visit to assess study drug dosing/tolerance and instruct on dosing for the upcoming second week of treatment. For the first 8 weeks of treatment, subjects will alternate between returning to the clinic for detailed assessments (Weeks 4 and 8) and receiving a telephone call from the Investigator team to assess safety and TTI-0102 dose (Weeks 2 and 6) and the potential need for an immediate unscheduled study visit. After the first 8 weeks of treatment, subjects will continue to return to the clinic for monthly assessments at Weeks 12, 16, 20. The Study Exit visit will occur at Week 24, and subjects will be offered to continue on an open-label extension study of TTI-0102. If a subject does not complete the study, they will be asked to return for a Study Exit visit 4 weeks after last study drug dose. Study Drug Dosing To prevent any manifestation of intolerance at the initiation of drug treatment, only half a dose (2.75 grams) will be given once a day for the first week of treatment. During the following weeks of treatment, patients will be given a full dose of 5.5 grams once a day. Interim Data Review After nine (9) patients have completed three months of treatment (the Week 12 visit) an interim data cut will take place to assess safety and potential efficacy signals. Even if no indications of efficacy are detected at this early stage, the trial itself will not be terminated unless there is a serious safety concern (i.e., protocol-defined Stopping Criteria are met).

Conditions

MELAS Syndrome; Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like Episodes (MELAS)

Outcome Measures

Primary Outcomes (2)

• Efficacy: Change in functional capacity

  12-minute walking test (12-MWT)

  Day 1/Baseline to Week 24/Study Exit

• Safety and Tolerability: Incidence of Treatment-Emergent Adverse Events

  Adverse Events

  Day 1/Baseline to Week 24/Study Exit

Secondary Outcomes (5)

• Efficacy: Fatigue

  Day 1/Baseline to Week 24/Study Exit

• Efficacy: Quality of Life (QoL)

  Day 1/Baseline to Week 24/Study Exit

• Pharmacokinetic parameter: Cmax

  Day 1/Baseline to Week 24/Study Exit

• Pharmacokinetic parameter: Tmax

  Day 1/Baseline to Week 24/Study Exit

• Pharmacokinetic parameter: AUC

  Day 1/Baseline to Week 24/Study Exit

Study Arms (2)

TTI-0102

EXPERIMENTAL

cysteamine-pantetheine disulfide

Drug: TTI-0102

Placebo

PLACEBO COMPARATOR

Pearlitol® 100 SD (mannitol)

Drug: Placebo

Interventions

TTI-0102 DRUG

(cysteamine-pantetheine disulfide)

TTI-0102

Placebo DRUG

Pearlitol® 100 SD (mannitol)

Placebo

Eligibility Criteria

• Age: 16 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patient or Patient's legally designated representative has given written informed consent before any study-related activities are carried out and is able to understand the full nature and purpose of the trial, including possible risks and adverse effects. Patient has provided assent according to local/institutional requirements.
• Males and females between 16 and 60 years of age at screening.
• Diagnosis of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), defined as:
• \- mtDNA mutation known to be associated with MELAS and MELAS phenotype (Emmanuele et al., 2022) including but not limited to: m.3243A\>G, m.13513G\>A, m.10191T\>C, m. 3271T\>C, m. 13136\_15374del, m. 8363G\>A. Mutation must have heteroplasmy \>50% characterized by mutation load in urinary epithelium or blood.
• AND
• \- two or more of the following clinical symptoms indicative of MELAS phenotype: diabetes, myopathy, seizures, at least one historic stroke-like episode, and exercise intolerance.
• Moderate disease severity defined as Newcastle Mitochondrial Disease Adult Scale (NMDAS) score between 15 to 45 inclusive.
• Able to complete a 12-minute walk test (12-MWT) distance of at least 150 meters and no more than 1000 meters within 30 days prior to, or at time of screening.
• Subjects regularly taking dietary supplements including but not limited to creatine, alpha-lipoic acid, CoQ10, B vitamins, levocarnitine shall have been taking them for at least 3 months pre-study and will agree to continue taking them throughout the study (from the Screening Visit to Study Exit).
• With respect to concomitant medications, the subject must:
• Be willing to abstain from initiating new dietary supplements and non-prescribed medications, except as permitted by the Investigator throughout the study.
• Be on a stable dose of medications prescribed for seizure management and prevention. Stable dose in this context means unchanged for at least 30 days prior to the Screening Visit.
• Willing and able to comply with study drug dosing requirements, i.e., able to ingest study drug solution orally.
• Female participants:
• Must be of nonchildbearing potential (i.e., surgically sterilized \[hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before the screening visit\]) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause, and a follicle-stimulating hormone \[FSH\] level \>40 IU/L at the screening visit), or

You may not qualify if:

• Documented diagnosis of concurrent inborn errors of metabolism.
• Non-elective hospitalization related to their mitochondrial disease or direct complication of disease within 60 days prior to the Screening Visit.
• Overt comorbidity preventing them from safely performing an exercise. In particular, patients suffering from cardiovascular, neurological disorders (e.g. ataxia, sequel blindness from pseudostroke, peripheral neuropathy) or advanced osteo-arthrosis.
• Treatment with taurine during the previous month, and not willing to discontinue for the duration of the trial.
• Platelet count, lymphocyte count or hemoglobin level below the lower limit of normal (LLN) at screening.
• Hepatic insufficiency with liver enzyme tests (alkaline phosphatase, AST or ALT) greater than 2.5 times to upper limit of normal (ULN) at screening.
• Bilirubin \> 1.2 g/dL at screening.
• Renal insufficiency, defined as 1) a requirement for chronic dialysis or 2) serum creatinine ≥1.2 mg/dl or creatinine clearance \<60 ml/min
• 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. Examples: malabsorption requiring TPN, chronic diarrhea, bouts of pseudo obstruction.
• Severe end-organ hypo-perfusion syndrome secondary to cardiac failure resulting in lactic acidosis.
• Patients with suspected elevated intracranial pressure, pseudotumor cerebri (PTC) and/or papilledema.
• History of angina, myocardial infarction, or cardiac surgery within 2 years prior to screening.
• History of drug or alcohol abuse.
• History of pancreatitis.

Sponsors & Collaborators

• Thiogenesis Therapeutics, Inc.: lead

Study Sites (2)

Angers University Hospital Center (CHU Angers)

Angers, 49100, France

RECRUITING

Radboud University Medical Center

Nijmegen, 6500 HB, Netherlands

RECRUITING

MeSH Terms

Conditions

MELAS Syndrome

Interventions

cysteamine-pantetheine disulfide

Condition Hierarchy (Ancestors)

Mitochondrial Encephalomyopathies; Mitochondrial Myopathies; Muscular Diseases; Musculoskeletal Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Neuromuscular Diseases; Vascular Diseases; Cardiovascular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Mitochondrial Diseases

Study Officials

• Patrice P Rioux, MD, PhD

  Thiogenesis Therapeutics, Inc.

  STUDY DIRECTOR

Central Study Contacts

TTI-MITO-001 Clinical Trial 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: Participants, investigator and sponsor will be blinded to active:placebo assignment and to PK measurements during the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multi-center, Randomized, Double-Blind, Placebo-Controlled Twelve (12) patients will be randomized on a 2:1 (active:placebo) ratio, with 8 receiving TTI-0102 and 4 receiving a placebo

Study Record Dates

• First Submitted: September 29, 2024
• First Posted: October 16, 2024
• Study Start: May 12, 2025
• Primary Completion: April 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: September 9, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); NL (1)