Methylmalonic AcidemiaPhase 2HERONCT04732429
Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia
A Phase 2 study testing HST5040 in people with Methylmalonic Acidemia and Propionic Acidemia, run by HemoShear Therapeutics at 16 sites in 3 countries.
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… Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Methylmalonic Acidemia, Propionic Acidemia
- What is being tested?
- HST5040
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 16 sitesin 3 countries
- Study dates
- 15 Mar 2021to 20 Oct 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
16 sites in 3 countries.
16 sites in 3 countries
United States14 sites
Emory University School of Medicine
Atlanta, Georgia, 30322
Boston Children's Hospital
Boston, Massachusetts, 02115
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Nationwide Children's Hospital
Columbus, Ohio, 43205
John P. and Kathrine G. McGovern Medical School
Houston, Texas, 77030
Children's Mercy Hospital Kansas City
Kansas City, Missouri, 64108
University of Minnesota
Minneapolis, Minnesota, 55455
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Yale
New Haven, Connecticut, 06520
University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213
University of Utah Hospital
Salt Lake City, Utah, 84132
Rady Children's Hospital
San Diego, California, 92123
Children's National Health System
Washington D.C., District of Columbia, 20010
Australia1 site
Royal Children's Hospital Melbourne
Parkville, Victoria, 3052
Saudi Arabia1 site
King Faisal Specialist Hospital and Research Centre
Riyadh, Riyadh Region, 11211
About this study
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
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.
- Conditions
- Methylmalonic Acidemia, Propionic Acidemia
- Being tested
- HST5040, Placebo
- Keywords
- Methylmalonic Acidemia, Propionic Acidemia, Organic Acidemia, Inborn errors of metabolism, PCCA, PCCB, Propionyl-coenzyme A carboxylase, MMUT, Methylmalonyl-CoA mutase, Metabolic disease, Genetic disease, HemoShear
- Medical subject headings
- Methylmalonic acidemia, Propionic Acidemia, Metabolism, Inborn Errors, Metabolic Diseases, Genetic Diseases, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HST5040Drug
Liquid solution
PlaceboDrug
Liquid solution
| Study group | Role | What they receive |
|---|---|---|
| Active Drug | Experimental | 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). Receives: Drug: HST5040 |
| Placebo | Experimental | Placebo in addition to standard of care. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in plasma 2-methylcitric acid (MCA) levels
nmol/mL
Measured: 6 months
Secondary outcomes (13)
Change in plasma propionyl-carnitine (3)
µmol/L
Measured: 6 months
Change in C3 to acetyl-carnitine ratio (C3:C2)
µmol/L
Measured: 6 months
Change in 3-OH propionate
g/mol
Measured: 6 months
Change in Methylmalonic acid (in MMA subjects)
nmol/L
Measured: 6 months
Change in NH3
nmol/L
Measured: 6 months
Anion Gap
mEq/L
Measured: 6 months
Pharmacokinetics parameters - Cmax
Maximum concentration (Cmax) after administration of HST5040
Measured: 6 months
Pharmacokinetics parameters - Tmax
Time of maximum concentration (Tmax)
Measured: 6 months
Pharmacokinetics parameters - AUC
Area under the concentration time curve (AUC)
Measured: 6 months
Oral Intake
Food diary - change from baseline to end of each dose level interval in oral intake
Measured: 6 months
Acute Metabolic Decompensations
Change in the total number of metabolic decompensation events requiring an emergency room (ER) visit of hospitalization
Measured: 6 months
MetabQoL 1.0 - Health Related Quality of Life (HRQOL)
Score 0-100 Scale. Higher Score indicates better HRQOL
Measured: 6 months
PedsQL 1.0 Family Impact Score - Health Related Quality of Life (HRQOL)
Score 0-100 Scale. Higher Score indicates better HRQOL
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2021
- Study start15 Mar 2021
- Primary completion20 Oct 2023
- Study completion20 Oct 2023
Why it stopped: The decision to terminate the study was based on business considerations by the Sponsor.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Methylmalonic AcidemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- HemoShear Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Patrick Horn, MD PhD, Study chair, HemoShear Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04732429
- Sponsor's protocol ID
- HST20-CL01
- Acronym
- HERO
- Status last verified
- Jan 2024
- First submitted
- 21 Jan 2021
- Last updated
- 5 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04732429
- Acronym / sponsor ID
- HERO / HST20-CL01
- Conditions
- Methylmalonic Acidemia, Propionic Acidemia
- Keywords
- Methylmalonic Acidemia, Propionic Acidemia, Organic Acidemia, Inborn errors of metabolism, PCCA, PCCB, Propionyl-coenzyme A carboxylase, MMUT
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The decision to terminate the study was based on business considerations by the Sponsor.
- Enrolment
- 26 participants (actual)
- Lead sponsor
- HemoShear TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 15 Mar 2021 (actual)
- Primary completion
- 20 Oct 2023 (actual)
- Study completion
- 20 Oct 2023 (actual)
- First posted
- 1 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Drug | Experimental | Drug: HST5040Part 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). |
| Placebo | Experimental | Drug: PlaceboPlacebo in addition to standard of care. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HST5040Liquid solution | Drug | Active Drug |
| PlaceboLiquid solution | Drug | Placebo |
Primary outcome
Change in plasma 2-methylcitric acid (MCA) levels
Time frame: 6 months
nmol/mL
13 secondary outcomes
Change in plasma propionyl-carnitine (3)
Time frame: 6 months
Change in C3 to acetyl-carnitine ratio (C3:C2)
Time frame: 6 months
Change in 3-OH propionate
Time frame: 6 months
Change in Methylmalonic acid (in MMA subjects)
Time frame: 6 months
Change in NH3
Time frame: 6 months
Anion Gap
Time frame: 6 months
Pharmacokinetics parameters - Cmax
Time frame: 6 months
Pharmacokinetics parameters - Tmax
Time frame: 6 months
Pharmacokinetics parameters - AUC
Time frame: 6 months
Oral Intake
Time frame: 6 months
Acute Metabolic Decompensations
Time frame: 6 months
MetabQoL 1.0 - Health Related Quality of Life (HRQOL)
Time frame: 6 months
PedsQL 1.0 Family Impact Score - Health Related Quality of Life (HRQOL)
Time frame: 6 months
Results and safety
The study was stopped early (reason given: The decision to terminate the study was based on business considerations by the Sponsor.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick Horn, MD PhD study chair
HemoShear Therapeutics, Inc.
16 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HST5040 in people with Methylmalonic Acidemia and Propionic Acidemia, run by HemoShear Therapeutics at 16 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, Australia, Saudi Arabia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The decision to terminate the study was based on business considerations by the Sponsor.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in plasma 2-methylcitric acid (MCA) levels (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2024.