Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia
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
- Eligible Ages
- Over 2 Years
- Eligible Genders
- Accepts Healthy Volunteers
- Confirmed diagnosis of symptomatic PA or MMA (Mutase) - Ages ≥ 2 years old. - Inadequate metabolic control while receiving standard of care (SoC) within the past 4 years. - 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.
- Phase 2
- Study Type
- Intervention Model
- Crossover Assignment
- Primary Purpose
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
|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.||
- HemoShear Therapeutics
Study ContactMavis Y Waller