By InvitationPhase 2

Sirolimus for Leigh Syndrome

United States15 participantsStarted 2025-02-27

Plain-language summary

The purpose of this study is to evaluate the safety and efficacy of the drug Sirolimus in participants with Leigh syndrome.

Age range6 Months – 55 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

✓. Genetically-confirmed diagnosis of Leigh syndrome with neurodevelopmental manifestations, which include documented developmental delay, developmental regression, or abnormal neurologic exam findings including but not limited to hypotonia, hypertonia, dystonia, chorea, nystagmus, ataxia, dysmetria, tremor or muscle weakness.
✓. Age 6 months to 55 years at the time of enrollment.
✓. Weight ≥ 5 kg at the time of enrollment.
✓. Adequate liver function as evidenced by total bilirubin \< 1.5x upper limit of normal (ULN) and liver function tests, alanine transaminase (ALT) and aspartate aminotransferase (AST), \< 3x ULN.
✓. Adequate renal function as evidenced by glomerular filtration rate (GFR) \> 60 mL/min/1.73m2 (cystatin C for pediatric population).
✓. Normal hematologic parameters as defined as:
✓. Absolute neutrophil count (ANC) ≥ 1.0 x 109/L
✓. Platelet count ≥ 100,000/mm3 (100 x 109/L)

✕. Cardiac ejection fraction ≤ 50 %, shortening fraction ≤ 25% on cardiac echocardiogram within one year of screening and/or severe end-organ hypo-perfusion syndrome (secondary to cardiac failure) resulting in lactic acidosis.
✕. Patients with implanted cardiac assist/medical devices (including pacemakers), unless device was implanted prophylactically, and the patient is clinically asymptomatic.
✕. In the opinion of the investigator, clinically significant ECG and/or echocardiogram alterations at the time of screening.
✕. Myocardial infarction within 6 months prior to enrollment.
✕. Symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or unstable coronary artery disease.
✕. Prior history of hypersensitivity to sirolimus or other mTOR (Mechanistic Target of Rapamycin inhibitors).
✕. Prior history of angioedema requiring treatment or cessation of a presumed causative agent.
✕. Planned surgical procedure during the study period.

Rate of Adverse Events

Timeframe: Up to 2.5 years

Rate of Intercurrent Infection and Hospitalization

Timeframe: Up to 2.5 years

Incidence of abnormal safety lab values

Timeframe: Up to 2.5 years

Sirolimus Trough Level

Timeframe: Up to 2.5 years

NCT IDNCT06843811

SponsorMatthew Demczko

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2027-12

Who can participate

Age range6 Months – 55 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

✓. Genetically-confirmed diagnosis of Leigh syndrome with neurodevelopmental manifestations, which include documented developmental delay, developmental regression, or abnormal neurologic exam findings including but not limited to hypotonia, hypertonia, dystonia, chorea, nystagmus, ataxia, dysmetria, tremor or muscle weakness.
✓. Age 6 months to 55 years at the time of enrollment.
✓. Weight ≥ 5 kg at the time of enrollment.
✓. Adequate liver function as evidenced by total bilirubin \< 1.5x upper limit of normal (ULN) and liver function tests, alanine transaminase (ALT) and aspartate aminotransferase (AST), \< 3x ULN.
✓. Adequate renal function as evidenced by glomerular filtration rate (GFR) \> 60 mL/min/1.73m2 (cystatin C for pediatric population).
✓. Normal hematologic parameters as defined as:
✓. Absolute neutrophil count (ANC) ≥ 1.0 x 109/L
✓. Platelet count ≥ 100,000/mm3 (100 x 109/L)

✕. Cardiac ejection fraction ≤ 50 %, shortening fraction ≤ 25% on cardiac echocardiogram within one year of screening and/or severe end-organ hypo-perfusion syndrome (secondary to cardiac failure) resulting in lactic acidosis.
✕. Patients with implanted cardiac assist/medical devices (including pacemakers), unless device was implanted prophylactically, and the patient is clinically asymptomatic.
✕. In the opinion of the investigator, clinically significant ECG and/or echocardiogram alterations at the time of screening.
✕. Myocardial infarction within 6 months prior to enrollment.
✕. Symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or unstable coronary artery disease.
✕. Prior history of hypersensitivity to sirolimus or other mTOR (Mechanistic Target of Rapamycin inhibitors).
✕. Prior history of angioedema requiring treatment or cessation of a presumed causative agent.
✕. Planned surgical procedure during the study period.