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.
Methylmalonic Acidemia, Propionic Acidemia
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.
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.
January 5, 2024
Primary Contact Information
For more information on this trial, visit clinicaltrials.gov.
For more information and to contact the study team: