A Phase 2 Open-label, Dose Escalation Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia Followed by a Randomized, Double-blind, Placebo-controlled, 2-period Crossover Study and an Open-label, Long-term Extension Study
| Registry | NCT04732429, acronym HERO |
|---|---|
| Status | Terminated - The decision to terminate the study was based on business considerations by the Sponsor. |
| Phase | Phase 2 |
| Study type | Interventional; randomized, crossover, masking: quadruple, treatment |
| Enrollment | 26 (Actual) |
| Sponsor | HemoShear Therapeutics (Industry) |
| Conditions | Methylmalonic Acidemia, Propionic Acidemia |
| Interventions | HST5040, Placebo (Drug) |
| Dates | start 2021-03-15, primary completion 2023-10-20, completion 2023-10-20, first posted 2021-02-01, last updated 2024-01-05 |
| Locations | 16 sites in United States, Australia, Saudi Arabia |
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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.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Active Drug | Experimental | Drug: HST5040 | 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 | Experimental | Drug: Placebo | Placebo in addition to standard of care. |
Sex: All, ages: 2 Years to any
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.
| Facility | City | Country | Status |
|---|---|---|---|
| Rady Children's Hospital | San Diego, California | United States | |
| Yale | New Haven, Connecticut | United States | |
| Children's National Health System | Washington D.C., District of Columbia | United States | |
| Emory University School of Medicine | Atlanta, Georgia | United States | |
| Ann & Robert H. Lurie Children's Hospital of Chicago | Chicago, Illinois | United States | |
| Boston Children's Hospital | Boston, Massachusetts | United States | |
| University of Minnesota | Minneapolis, Minnesota | United States | |
| Children's Mercy Hospital Kansas City | Kansas City, Missouri | United States | |
| University Hospitals Cleveland Medical Center | Cleveland, Ohio | United States | |
| Nationwide Children's Hospital | Columbus, Ohio | United States | |
| University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh | Pittsburgh, Pennsylvania | United States | |
| Vanderbilt University Medical Center | Nashville, Tennessee | United States | |
| John P. and Kathrine G. McGovern Medical School | Houston, Texas | United States | |
| University of Utah Hospital | Salt Lake City, Utah | United States | |
| Royal Children's Hospital Melbourne | Parkville, Victoria | Australia | |
| King Faisal Specialist Hospital and Research Centre | Riyadh, Riyadh Region | Saudi Arabia |