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.
March 9, 2023
Primary Contact Information
Mavis Y Waller
Allison J Armstrong
For more information on this trial, visit clinicaltrials.gov.
For more information and to contact the study team: