NCT04732429: HERO

Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia

Terminated Phase 2 Last updated 5 January 2024

What this trial tests

Phase 2 trial testing HST5040 in Methylmalonic Acidemia in 26 participants. Terminated before completion.

Timeline

15 March 2021

Primary endpoint
20 October 2023

20 October 2023

Quick facts

Lead sponsor	HemoShear Therapeutics
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	quadruple
Primary purpose	treatment
Enrollment	26
Start date	15 March 2021
Primary completion	20 October 2023
Estimated completion	20 October 2023
Sites	16 locations across Saudi Arabia, United States, Australia

Drugs / interventions tested

• HST5040 — full drug profile →
• Placebo

Conditions studied

• Methylmalonic Acidemia — all drugs for Methylmalonic Acidemia →
• Propionic Acidemia — all drugs for Propionic Acidemia →

Sponsor

HemoShear Therapeutics — full company profile →

Who can join

2 and older, any sex, with Methylmalonic Acidemia or Propionic Acidemia. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Biomarkers for drug development in propionic and methylmalonic acidemias.
   Longo N, Sass JO, Jurecka A, Vockley J. · · 2022 · cited 30× · PMID 35038174 · DOI 10.1002/jimd.12478
2. Mitochondrial disease, mitophagy, and cellular distress in methylmalonic acidemia.
   Luciani A, Denley MCS, Govers LP, Sorrentino V, et al · · 2021 · cited 25× · PMID 34524466 · DOI 10.1007/s00018-021-03934-3
3. Metabolic toxicity and neurological dysfunction in methylmalonic acidemia: from mechanisms to therapeutics.
   Du M, Li M, Wu S, Wu X, et al · · 2025 · PMID 41299235 · DOI 10.1186/s10020-025-01395-z