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Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia (HERO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04732429
Recruitment Status : Recruiting
First Posted : February 1, 2021
Last Update Posted : March 9, 2023
Information provided by (Responsible Party):
HemoShear Therapeutics

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.

Condition or disease Intervention/treatment Phase
Methylmalonic Acidemia Propionic Acidemia Drug: HST5040 Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Arm Intervention/treatment
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).
Drug: HST5040
Liquid solution

Experimental: Placebo
Placebo in addition to standard of care.
Drug: Placebo
Liquid solution

Primary Outcome Measures :
  1. Change in plasma 2-methylcitric acid (MCA) levels [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Change in plasma propionyl-carnitine (3) [ Time Frame: 6 months ]

  2. Change in C3 to acetyl-carnitine ratio (C3:C2) [ Time Frame: 6 months ]

  3. Change in 3-OH propionate [ Time Frame: 6 months ]

  4. Change in Methylmalonic acid (in MMA subjects) [ Time Frame: 6 months ]

  5. Change in NH3 [ Time Frame: 6 months ]

  6. Anion Gap [ Time Frame: 6 months ]

  7. Pharmacokinetics parameters - Cmax [ Time Frame: 6 months ]
    Maximum concentration (Cmax) after administration of HST5040

  8. Pharmacokinetics parameters - Tmax [ Time Frame: 6 months ]
    Time of maximum concentration (Tmax)

  9. Pharmacokinetics parameters - AUC [ Time Frame: 6 months ]
    Area under the concentration time curve (AUC)

  10. Oral Intake [ Time Frame: 6 months ]
    Food diary - change from baseline to end of each dose level interval in oral intake

  11. Acute Metabolic Decompensations [ Time Frame: 6 months ]
    Change in the total number of metabolic decompensation events requiring an emergency room (ER) visit of hospitalization

  12. MetabQoL 1.0 - Health Related Quality of Life (HRQOL) [ Time Frame: 6 months ]
    Score 0-100 Scale. Higher Score indicates better HRQOL

  13. 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

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

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

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Contact: Mavis Y Waller 833-975-3559 waller@hemoshear.com
Contact: Allison J Armstrong 833-975-3559 Armstrong@hemoshear.com

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United States, California
Rady Children's Hospital Recruiting
San Diego, California, United States, 92123
Contact: Sergio Garcia Crosthwaite    858-576-1700    sgarciacrosthwaite@rchsd.org   
United States, Connecticut
Yale Recruiting
New Haven, Connecticut, United States, 06520
Contact: Michele Jasne    203-785-4945    michele.jasne@yale.edu   
United States, District of Columbia
Children's National Health System Recruiting
Washington, District of Columbia, United States, 20010
Contact: Sonja Duncan       sduncan@childrensnational.org   
United States, Georgia
Emory University School of Medicine Recruiting
Atlanta, Georgia, United States, 30322
Contact: Eleanor Botha    404-778-8517    egeller@emory.edu   
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Carolyn Serbinski    312-227-4391    cserbinski@luriechildrens.org   
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.soules@helendevoschildrens.org   
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Sara Elsbecker    612-626-5275    selsbeck10@umphysicians.umn.edu   
United States, Missouri
Children's Mercy Hospital Kansas City Recruiting
Kansas City, Missouri, United States, 64108
Contact: Kemi Lewis    816-302-8419    kjlewis@cmh.edu   
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    leeanna.melton@vumc.org   
United States, Utah
University of Utah Hospital Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Kenzie Fait    801-585-7160    kenzie.fait@hsc.utah.edu   
Australia, Victoria
Royal Children's Hospital Melbourne Recruiting
Parkville, Victoria, Australia, 3052
Contact: Beath Kara    +61 03 9345 6251    kara.beath@mcri.edu.au   
Contact: Jessica Yeo    +61 03 9345 6251    jessica.yeo@mcri.edu.au   
Sponsors and Collaborators
HemoShear Therapeutics
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Study Chair: Patrick Horn, MD PhD HemoShear Therapeutics, Inc.
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Responsible Party: HemoShear Therapeutics
ClinicalTrials.gov Identifier: NCT04732429    
Other Study ID Numbers: HST20-CL01
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by HemoShear Therapeutics:
Methylmalonic Acidemia
Propionic Acidemia
Organic Acidemia
Inborn errors of metabolism
Propionyl-coenzyme A carboxylase
Methylmalonyl-CoA mutase
Metabolic disease
Genetic disease
Additional relevant MeSH terms:
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Amino Acid Metabolism, Inborn Errors
Propionic Acidemia
Acid-Base Imbalance
Metabolic Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn