Vanderbilt Clinical Trials

Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia

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

Methylmalonic Acidemia
Propionic Acidemia

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. - 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.

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

Arm	Description	Assigned 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

More Details

Status: Terminated
Sponsor: HemoShear Therapeutics

Study Contact

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.