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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04732429




Registration number
NCT04732429
Ethics application status
Date submitted
21/01/2021
Date registered
1/02/2021

Titles & IDs
Public title
Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia
Scientific 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
Secondary ID [1] 0 0
HST20-CL01
Universal Trial Number (UTN)
Trial acronym
HERO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Methylmalonic Acidemia 0 0
Propionic Acidemia 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Renal and Urogenital 0 0 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - HST5040
Treatment: Drugs - Placebo

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).

Experimental: Placebo - Placebo in addition to standard of care.


Treatment: Drugs: HST5040
Liquid solution

Treatment: Drugs: Placebo
Liquid solution
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in plasma 2-methylcitric acid (MCA) levels
Timepoint [1] 0 0
6 months
Secondary outcome [1] 0 0
Change in plasma propionyl-carnitine (3)
Timepoint [1] 0 0
6 months
Secondary outcome [2] 0 0
Change in C3 to acetyl-carnitine ratio (C3:C2)
Timepoint [2] 0 0
6 months
Secondary outcome [3] 0 0
Change in 3-OH propionate
Timepoint [3] 0 0
6 months
Secondary outcome [4] 0 0
Change in Methylmalonic acid (in MMA subjects)
Timepoint [4] 0 0
6 months
Secondary outcome [5] 0 0
Change in NH3
Timepoint [5] 0 0
6 months
Secondary outcome [6] 0 0
Anion Gap
Timepoint [6] 0 0
6 months
Secondary outcome [7] 0 0
Pharmacokinetics parameters - Cmax
Timepoint [7] 0 0
6 months
Secondary outcome [8] 0 0
Pharmacokinetics parameters - Tmax
Timepoint [8] 0 0
6 months
Secondary outcome [9] 0 0
Pharmacokinetics parameters - AUC
Timepoint [9] 0 0
6 months
Secondary outcome [10] 0 0
Oral Intake
Timepoint [10] 0 0
6 months
Secondary outcome [11] 0 0
Acute Metabolic Decompensations
Timepoint [11] 0 0
6 months
Secondary outcome [12] 0 0
MetabQoL 1.0 - Health Related Quality of Life (HRQOL)
Timepoint [12] 0 0
6 months
Secondary outcome [13] 0 0
PedsQL 1.0 Family Impact Score - Health Related Quality of Life (HRQOL)
Timepoint [13] 0 0
6 months

Eligibility
Key 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.
Minimum age
2 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
20/10/2023
Sample size
Target
Accrual to date
Final
26
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Royal Children's Hospital Melbourne - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Utah
Country [14] 0 0
Saudi Arabia
State/province [14] 0 0
Riyadh

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
HemoShear Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Patrick Horn, MD PhD
Address 0 0
HemoShear Therapeutics, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04732429