Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia

Propionic Acidemia Clinical Trial

— HERO  

Official 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04732429
• Other study ID #: HST20-CL01
• Status: Terminated
• Phase: Phase 2
• 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
• 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.

Related Conditions & MeSH terms

• Acidosis
• Amino Acid Metabolism, Inborn Errors
• Methylmalonic Acidemia
• Propionic Acidemia

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