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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT04732429
Other study ID # HST20-CL01
Secondary ID
Status Terminated
Phase Phase 2
First received
Last updated
Start date March 15, 2021
Est. completion date October 20, 2023

Study information

Verified date January 2024
Source HemoShear Therapeutics
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Recruitment information / eligibility

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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
HST5040
Liquid solution
Placebo
Liquid solution

Locations

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

Sponsors (1)

Lead Sponsor Collaborator
HemoShear Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Saudi Arabia, 

Outcome

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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