ABI-009 (Nab-sirolimus) in Patients With Genetically-confirmed Leigh or Leigh-like Syndrome

NCT03747328 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: LS007
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

A phase 2a, open-label study to evaluate the safety, tolerability, and clinical activity of ABI-009 (nab-sirolimus) in patients with genetically-confirmed Leigh or Leigh-like syndrome

Conditions

Leigh Syndrome

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment emergent adverse events in pediatric patients with genetically-confirmed Leigh or Leigh-like syndrome administered ABI-009 intravenously (IV)

  Adverse events will be measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.

  Up to 24 weeks

Study Arms (1)

ABI-009

EXPERIMENTAL

nanoparticle albumin bound sirolimus (ABI-009). Dose levels 1, 2.5, 5 and 10 mg/m2 given weekly for 8 cycles of ABI-009 (each cycle is weekly dosing for 2 weeks followed by a week of rest (qw2/3))

Drug: ABI-009

Interventions

ABI-009 DRUG

nanoparticle albumin bound sirolimus

ABI-009

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Diagnosis of genetically-confirmed Leigh or Leigh-like syndrome, as well as documented clinical evidence (including demonstrated neurologic manifestations) of the syndrome, as confirmed by the investigator.
• Moderate disease severity based on NPMDS score of \>15 on Sections I through III, inclusive.
• Male or female patients, ≥2 and ≤17 years of age at the time of enrollment.
• Body weight ≥5 kg (11 lbs) at the time of enrollment.
• Chronic, stable disease, as determined by the investigator, for a minimum of 3 months prior to enrollment. This includes, but is not limited to, patients without hospitalizations or emergency room visits, or fever \<101 F, and/or acute illness.
• Adequate liver function:
• Total bilirubin ≤1.5 x upper limit of normal (ULN) mg/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<3 x ULN.
• Adequate renal function as defined by serum creatinine \<ULN for each individual patient's age category.
• Adequate biological parameters:
• Absolute neutrophil count (ANC) ≥1.5 × 109/L
• Platelet count ≥100,000/mm3 (100 × 109/L)
• Hemoglobin ≥9 g/dL.
• Adequate immunoglobulin levels (IgG, IgA, IgM) that, in the opinion of the investigator, will not place the patient at increased risk for infection.
• Serum amylase and lipase \<2 x ULN.

You may not qualify if:

• Renal insufficiency that, in the opinion of the investigator, requires or may require dialysis during the treatment and follow-up periods.
• Cardiac ejection fraction/shortening fraction ≤50 % 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 ECHO findings 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 exposure to ABI-009, sirolimus, everolimus, or any other known rapamycin derivative, or previous treatment with any known mTOR inhibitor.
• Patients who are breast feeding or have a confirmed or suspected pregnancy.
• Treatment with any investigational drug (ie, a drug for which there is no approved indication), including an investigational drug for mitochondrial disease within 1 month prior to receiving the first dose of study drug (or within 3 months for a trial with an investigational biologic).
• Disease-related surgical intervention within 1 month prior to the first dose of study drug.
• Use of supplements that are contraindicated in the opinion of investigator, including super-fortified foods and/or beverages that include coenzyme Q10, Vitamin C, Vitamin E, and/or idebenone, etc, unless receiving stable doses for a minimum of 30 days prior to enrollment. Changes to mitochondrial dietary supplements or their doses for 30 days prior to enrollment.
• Known hypersensitivity to ABI-009 (nab-sirolimus; ie, sirolimus and albumin), to any of its excipients, or to any known rapamycin derivative or known mTOR inhibitor.
• Patients with confirmed or suspected increased intracranial pressure, pseudotumor cerebri (PTC)/idiopathic intracranial hypertension, and/or papilledema.
• Any uncontrolled serious illness or psychiatric condition, medical condition, or other medical history, including abnormal laboratory test results which, in the opinion of the investigator, would be likely to interfere with the patient's participation in the study, or with the interpretation of the results of the study.
• Currently active malignancy (other than adequately treated non-melanoma skin cancers \[ie, squamous cell and/or basal cell carcinoma\], 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 ≥1 year.

Sponsors & Collaborators

• Aadi Bioscience, Inc.: lead

MeSH Terms

Conditions

Leigh Disease

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2018
• First Posted: November 20, 2018
• Study Start: April 30, 2022
• Primary Completion: December 31, 2024
• Study Completion: March 31, 2025
• Last Updated: February 1, 2022

Record last verified: 2022-01