Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 2 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Active Drug
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).
  • Drug: HST5040
    Liquid solution
Experimental
Placebo
Placebo in addition to standard of care.
  • Drug: Placebo
    Liquid solution

Recruiting Locations

Vanderbilt University Medical Center
Nashville, Tennessee 37232
Contact:
LeeAnna Melton
615-343-6761
leeanna.melton@vumc.org

More Details

Status
Recruiting
Sponsor
HemoShear Therapeutics

Study Contact

Mavis Y Waller
833-975-3559
waller@hemoshear.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.