Propionic Acidemia Clinical Trial
— HEROOfficial title:
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
Verified date | January 2024 |
Source | HemoShear Therapeutics |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Terminated |
Enrollment | 26 |
Est. completion date | October 20, 2023 |
Est. primary completion date | October 20, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 2 Years and older |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
Australia | Royal Children's Hospital Melbourne | Parkville | Victoria |
Saudi Arabia | King Faisal Specialist Hospital and Research Centre | Riyadh | |
United States | Emory University School of Medicine | Atlanta | Georgia |
United States | Boston Children's Hospital | Boston | Massachusetts |
United States | Ann & Robert H. Lurie Children's Hospital of Chicago | Chicago | Illinois |
United States | University Hospitals Cleveland Medical Center | Cleveland | Ohio |
United States | Nationwide Children's Hospital | Columbus | Ohio |
United States | John P. and Kathrine G. McGovern Medical School | Houston | Texas |
United States | Children's Mercy Hospital Kansas City | Kansas City | Missouri |
United States | University of Minnesota | Minneapolis | Minnesota |
United States | Vanderbilt University Medical Center | Nashville | Tennessee |
United States | Yale | New Haven | Connecticut |
United States | University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania |
United States | University of Utah Hospital | Salt Lake City | Utah |
United States | Rady Children's Hospital | San Diego | California |
United States | Children's National Health System | Washington | District of Columbia |
Lead Sponsor | Collaborator |
---|---|
HemoShear Therapeutics |
United States, Australia, Saudi Arabia,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in plasma 2-methylcitric acid (MCA) levels | nmol/mL | 6 months | |
Secondary | Change in plasma propionyl-carnitine (3) | µmol/L | 6 months | |
Secondary | Change in C3 to acetyl-carnitine ratio (C3:C2) | µmol/L | 6 months | |
Secondary | Change in 3-OH propionate | g/mol | 6 months | |
Secondary | Change in Methylmalonic acid (in MMA subjects) | nmol/L | 6 months | |
Secondary | Change in NH3 | nmol/L | 6 months | |
Secondary | Anion Gap | mEq/L | 6 months | |
Secondary | Pharmacokinetics parameters - Cmax | Maximum concentration (Cmax) after administration of HST5040 | 6 months | |
Secondary | Pharmacokinetics parameters - Tmax | Time of maximum concentration (Tmax) | 6 months | |
Secondary | Pharmacokinetics parameters - AUC | Area under the concentration time curve (AUC) | 6 months | |
Secondary | Oral Intake | Food diary - change from baseline to end of each dose level interval in oral intake | 6 months | |
Secondary | Acute Metabolic Decompensations | Change in the total number of metabolic decompensation events requiring an emergency room (ER) visit of hospitalization | 6 months | |
Secondary | MetabQoL 1.0 - Health Related Quality of Life (HRQOL) | Score 0-100 Scale. Higher Score indicates better HRQOL | 6 months | |
Secondary | PedsQL 1.0 Family Impact Score - Health Related Quality of Life (HRQOL) | Score 0-100 Scale. Higher Score indicates better HRQOL | 6 months |
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