Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia

• Status: Recruiting
• Trial end date: 2026-01-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: HemoShear Therapeutics

Criteria

Inclusion Criteria:

• 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.

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.