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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04732429




Registration number
NCT04732429
Ethics application status
Date submitted
21/01/2021
Date registered
1/02/2021
Date last updated
5/01/2024

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
Terminated
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
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04732429
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04732429