Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia (HERO)
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|ClinicalTrials.gov Identifier: NCT04732429|
Recruitment Status : Recruiting
First Posted : February 1, 2021
Last Update Posted : March 9, 2023
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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.
|Condition or disease||Intervention/treatment||Phase|
|Methylmalonic Acidemia Propionic Acidemia||Drug: HST5040 Drug: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
|Actual Study Start Date :||March 15, 2021|
|Estimated Primary Completion Date :||March 31, 2023|
|Estimated Study Completion Date :||January 31, 2026|
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).
Placebo in addition to standard of care.
- Change in plasma 2-methylcitric acid (MCA) levels [ Time Frame: 6 months ]nmol/mL
- Change in plasma propionyl-carnitine (3) [ Time Frame: 6 months ]µmol/L
- Change in C3 to acetyl-carnitine ratio (C3:C2) [ Time Frame: 6 months ]µmol/L
- Change in 3-OH propionate [ Time Frame: 6 months ]g/mol
- Change in Methylmalonic acid (in MMA subjects) [ Time Frame: 6 months ]nmol/L
- Change in NH3 [ Time Frame: 6 months ]nmol/L
- Anion Gap [ Time Frame: 6 months ]mEq/L
- Pharmacokinetics parameters - Cmax [ Time Frame: 6 months ]Maximum concentration (Cmax) after administration of HST5040
- Pharmacokinetics parameters - Tmax [ Time Frame: 6 months ]Time of maximum concentration (Tmax)
- Pharmacokinetics parameters - AUC [ Time Frame: 6 months ]Area under the concentration time curve (AUC)
- Oral Intake [ Time Frame: 6 months ]Food diary - change from baseline to end of each dose level interval in oral intake
- Acute Metabolic Decompensations [ Time Frame: 6 months ]Change in the total number of metabolic decompensation events requiring an emergency room (ER) visit of hospitalization
- MetabQoL 1.0 - Health Related Quality of Life (HRQOL) [ Time Frame: 6 months ]Score 0-100 Scale. Higher Score indicates better HRQOL
- PedsQL 1.0 Family Impact Score - Health Related Quality of Life (HRQOL) [ Time Frame: 6 months ]Score 0-100 Scale. Higher Score indicates better HRQOL
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||2 Years and older (Child, Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04732429
|Contact: Mavis Y Wallerfirstname.lastname@example.org|
|Contact: Allison J Armstrong||833-975-3559||Armstrong@hemoshear.com|
|United States, California|
|Rady Children's Hospital||Recruiting|
|San Diego, California, United States, 92123|
|Contact: Sergio Garcia Crosthwaite 858-576-1700 email@example.com|
|United States, Connecticut|
|New Haven, Connecticut, United States, 06520|
|Contact: Michele Jasne 203-785-4945 firstname.lastname@example.org|
|United States, District of Columbia|
|Children's National Health System||Recruiting|
|Washington, District of Columbia, United States, 20010|
|Contact: Sonja Duncan email@example.com|
|United States, Georgia|
|Emory University School of Medicine||Recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: Eleanor Botha 404-778-8517 firstname.lastname@example.org|
|United States, Illinois|
|Ann & Robert H. Lurie Children's Hospital of Chicago||Recruiting|
|Chicago, Illinois, United States, 60611|
|Contact: Carolyn Serbinski 312-227-4391 email@example.com|
|United States, Massachusetts|
|Boston Children's Hospital||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Lora Pixley 617-919-7632 Lora.Pixley@childrens.harvard.edu|
|United States, Michigan|
|Helen DeVos Children's Hospital||Recruiting|
|Grand Rapids, Michigan, United States, 49503|
|Contact: Nicole Soules 616-486-2064 Nicole.firstname.lastname@example.org|
|United States, Minnesota|
|University of Minnesota||Recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Contact: Sara Elsbecker 612-626-5275 email@example.com|
|United States, Missouri|
|Children's Mercy Hospital Kansas City||Recruiting|
|Kansas City, Missouri, United States, 64108|
|Contact: Kemi Lewis 816-302-8419 firstname.lastname@example.org|
|United States, Ohio|
|University Hospitals Cleveland Medical Center||Recruiting|
|Cleveland, Ohio, United States, 44106|
|Contact: Genya Kisin 216-286-9202 Genya.Kisin@UHhospitals.org|
|United States, Pennsylvania|
|University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15213|
|Contact: Elizabeth McCraken 412-692-5662 Elizabeth.McCracken@chp.edu|
|United States, Tennessee|
|Vanderbilt University Medical Center||Recruiting|
|Nashville, Tennessee, United States, 37232|
|Contact: LeeAnna Melton 615-343-6761 email@example.com|
|United States, Utah|
|University of Utah Hospital||Recruiting|
|Salt Lake City, Utah, United States, 84132|
|Contact: Kenzie Fait 801-585-7160 firstname.lastname@example.org|
|Royal Children's Hospital Melbourne||Recruiting|
|Parkville, Victoria, Australia, 3052|
|Contact: Beath Kara +61 03 9345 6251 email@example.com|
|Contact: Jessica Yeo +61 03 9345 6251 firstname.lastname@example.org|
|Study Chair:||Patrick Horn, MD PhD||HemoShear Therapeutics, Inc.|
|Responsible Party:||HemoShear Therapeutics|
|Other Study ID Numbers:||
|First Posted:||February 1, 2021 Key Record Dates|
|Last Update Posted:||March 9, 2023|
|Last Verified:||January 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Inborn errors of metabolism
Propionyl-coenzyme A carboxylase
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn