Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia (HERO)
Methylmalonic Acidemia, Propionic Acidemia
About this trial
This is an interventional treatment trial for Methylmalonic Acidemia focused on measuring Methylmalonic Acidemia, Propionic Acidemia, Organic Acidemia, Inborn errors of metabolism, PCCA, PCCB, Propionyl-coenzyme A carboxylase, MMUT, Methylmalonyl-CoA mutase, Metabolic disease, Genetic disease, HemoShear
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.
Sites / Locations
- Rady Children's HospitalRecruiting
- YaleRecruiting
- Children's National Health SystemRecruiting
- Emory University School of MedicineRecruiting
- Ann & Robert H. Lurie Children's Hospital of ChicagoRecruiting
- Boston Children's HospitalRecruiting
- University of MinnesotaRecruiting
- Children's Mercy Hospital Kansas CityRecruiting
- University Hospitals Cleveland Medical CenterRecruiting
- Nationwide Children's HospitalRecruiting
- University of Pittsburgh Medical Center - Children's Hospital of PittsburghRecruiting
- Vanderbilt University Medical CenterRecruiting
- John P. and Kathrine G. McGovern Medical SchoolRecruiting
- University of Utah HospitalRecruiting
- Royal Children's Hospital MelbourneRecruiting
- King Faisal Specialist Hospital and Research CentreRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Active Drug
Placebo
Part B is the 6-month, randomized, double-blind (Subject/Investigator/Sponsor), placebo-controlled, 2-period crossover study consisting of 2 intervention periods of 12 weeks each to evaluate the safety and efficacy of the optimal dose of HST5040 in PA and MMA subjects ≥ 2 years old (N = minimum 12) in addition to SoC determined in Part A (within-subject dose escalation).
Placebo in addition to standard of care.