Summary
This is an interventional study to assess the safety, PK, and efficacy of HST5040 in 12 subjects - 6 with Methylmalonic Acidemia (MMA) and 6 with Propionic Acidemia (PA). The study consists of 3 parts: * Part A: Open-label, within-subject, dose escalation study in PA and MMA subjects ≥ 2 years old to identify a safe and pharmacologically active (optimal) dose of HST5040 for use in Part B. Subjects will continue in a Part A open-label extension until all subjects complete Part A and the optimal dose of HST5040 is identified for use in Part B. * Part B: 6-month, randomized, double-blind, placebo-controlled, 2-period crossover in the same subjects from Part A to evaluate safety and efficacy of the optimal dose of HST5040 in addition to standard of care (SoC). * Part C: open-label long-term extension study in PA and MMA subjects ≥ 2 years old (N = approximately 12, 6 each) to evaluate the long-term safety and efficacy of the optimal dose of HST5040. This study will determine whether HST5040 can improve levels of disease-associated toxins that accumulate in patients with PA and MMA.
Conditions
Methylmalonic Acidemia, Propionic Acidemia
Recruitment Status
TERMINATED
Eligibility Criteria
Inclusion Criteria:
* Confirmed diagnosis of symptomatic PA or MMA (Mutase)
* Ages ≥ 2 years old.
* History of Inadequate metabolic control while receiving standard of care (SoC).
* Plasma MCA concentration \> 3x upper limit of normal of the reference range at screening.
* Stable supplementation dose of carnitine for at least 1 week prior to the entry in the study.
Exclusion Criteria:
* Moderate-to-severely impaired cardiac function with LVEF \< 45% by ECHO.
* Clinically significant arrhythmia by Holter monitor.
* QTcF \> 450 msec
* Moderate to severe chronic kidney disease with estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73m2.
* Exposure to any investigational therapy, apart for a COVID-19 vaccine, within the past 6 months prior to study entry.
* Exposure to gene therapy for PA or MMA at any time prior to study entry.
* History of organ transplantation (Part A and B only)
* History of severe allergic or anaphylactic reactions to any of the components of HST5040.
Intervention
Intervention Type
Intervention Name
DRUG
HST5040
DRUG
Placebo
Phase
PHASE2
Gender
ALL
Min Age
2 Years
Max Age
N/A
Download Date
2024-01-05
Principal Investigator
N/A
Primary Contact Information
For more information on this trial, visit clinicaltrials.gov.
Contact
For more information and to contact the study team: