Back to resultsStudy of HST5040 in Subjects With Propionic or Methylmalonic Acidemia (HERO)
Primary Purpose
Methylmalonic Acidemia, Propionic Acidemia
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
HST5040
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Methylmalonic Acidemia focused on measuring 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
Eligibility Criteria
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.
Sites / Locations
- Rady Children's HospitalRecruiting
- YaleRecruiting
- Children's National Health SystemRecruiting
- Emory University School of MedicineRecruiting
- Ann & Robert H. Lurie Children's Hospital of ChicagoRecruiting
- Boston Children's HospitalRecruiting
- University of MinnesotaRecruiting
- Children's Mercy Hospital Kansas CityRecruiting
- University Hospitals Cleveland Medical CenterRecruiting
- Nationwide Children's HospitalRecruiting
- University of Pittsburgh Medical Center - Children's Hospital of PittsburghRecruiting
- Vanderbilt University Medical CenterRecruiting
- John P. and Kathrine G. McGovern Medical SchoolRecruiting
- University of Utah HospitalRecruiting
- Royal Children's Hospital MelbourneRecruiting
- King Faisal Specialist Hospital and Research CentreRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Active Drug
Placebo
Arm Description
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.
Outcomes
Primary Outcome Measures
Change in plasma 2-methylcitric acid (MCA) levels
nmol/mL
Secondary Outcome Measures
Change in plasma propionyl-carnitine (3)
µmol/L
Change in C3 to acetyl-carnitine ratio (C3:C2)
µmol/L
Change in 3-OH propionate
g/mol
Change in Methylmalonic acid (in MMA subjects)
nmol/L
Change in NH3
nmol/L
Anion Gap
mEq/L
Pharmacokinetics parameters - Cmax
Maximum concentration (Cmax) after administration of HST5040
Pharmacokinetics parameters - Tmax
Time of maximum concentration (Tmax)
Pharmacokinetics parameters - AUC
Area under the concentration time curve (AUC)
Oral Intake
Food diary - change from baseline to end of each dose level interval in oral intake
Acute Metabolic Decompensations
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)
Score 0-100 Scale. Higher Score indicates better HRQOL
PedsQL 1.0 Family Impact Score - Health Related Quality of Life (HRQOL)
Score 0-100 Scale. Higher Score indicates better HRQOL
Full Information
NCT ID
NCT04732429
First Posted
January 21, 2021
Last Updated
September 27, 2023
Sponsor
HemoShear Therapeutics
1. Study Identification
Unique Protocol Identification Number
NCT04732429
Brief Title
Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia
Acronym
HERO
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 15, 2021 (Actual)
Primary Completion Date
March 30, 2024 (Anticipated)
Study Completion Date
January 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
HemoShear Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Methylmalonic Acidemia, Propionic Acidemia
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Active Drug
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo
Arm Type
Experimental
Arm Description
Placebo in addition to standard of care.
Intervention Type
Drug
Intervention Name(s)
HST5040
Intervention Description
Liquid solution
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Liquid solution
Primary Outcome Measure Information:
Title
Change in plasma 2-methylcitric acid (MCA) levels
Description
nmol/mL
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Change in plasma propionyl-carnitine (3)
Description
µmol/L
Time Frame
6 months
Title
Change in C3 to acetyl-carnitine ratio (C3:C2)
Description
µmol/L
Time Frame
6 months
Title
Change in 3-OH propionate
Description
g/mol
Time Frame
6 months
Title
Change in Methylmalonic acid (in MMA subjects)
Description
nmol/L
Time Frame
6 months
Title
Change in NH3
Description
nmol/L
Time Frame
6 months
Title
Anion Gap
Description
mEq/L
Time Frame
6 months
Title
Pharmacokinetics parameters - Cmax
Description
Maximum concentration (Cmax) after administration of HST5040
Time Frame
6 months
Title
Pharmacokinetics parameters - Tmax
Description
Time of maximum concentration (Tmax)
Time Frame
6 months
Title
Pharmacokinetics parameters - AUC
Description
Area under the concentration time curve (AUC)
Time Frame
6 months
Title
Oral Intake
Description
Food diary - change from baseline to end of each dose level interval in oral intake
Time Frame
6 months
Title
Acute Metabolic Decompensations
Description
Change in the total number of metabolic decompensation events requiring an emergency room (ER) visit of hospitalization
Time Frame
6 months
Title
MetabQoL 1.0 - Health Related Quality of Life (HRQOL)
Description
Score 0-100 Scale. Higher Score indicates better HRQOL
Time Frame
6 months
Title
PedsQL 1.0 Family Impact Score - Health Related Quality of Life (HRQOL)
Description
Score 0-100 Scale. Higher Score indicates better HRQOL
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mavis Y Waller
Phone
833-975-3559
Email
waller@hemoshear.com
First Name & Middle Initial & Last Name or Official Title & Degree
Allison J Armstrong
Phone
833-975-3559
Email
Armstrong@hemoshear.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Horn, MD PhD
Organizational Affiliation
HemoShear Therapeutics, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Rady Children's Hospital
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sergio Garcia Crosthwaite
Phone
858-576-1700
Email
sgarciacrosthwaite@rchsd.org
Facility Name
Yale
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michele Jasne
Phone
203-785-4945
Email
michele.jasne@yale.edu
Facility Name
Children's National Health System
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mirian Naybor
Phone
202-476-6659
Email
mnaybor@childrensnational.org
Facility Name
Emory University School of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eleanor Botha
Phone
404-778-8517
Email
egeller@emory.edu
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carolyn Raski
Phone
312-227-4391
Email
craski@luriechildrens.org
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sarah Clemons
Phone
617-919-5125
Email
Sarah.Clemons@childrens.harvard.edu
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sara Elsbecker
Phone
612-626-5275
Email
selsbeck10@umphysicians.umn.edu
Facility Name
Children's Mercy Hospital Kansas City
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
jennifer Dolan
Phone
816-760-8876
Email
jdolan@cmh.edu
Facility Name
University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Genya Kisin
Phone
216-286-9202
Email
Genya.Kisin@UHhospitals.org
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lauren Pavlechko
Phone
614-722-6797
Email
lauren.pavlechko@nationwidechildrens.org
Facility Name
University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elizabeth McCraken
Phone
412-692-5662
Email
Elizabeth.McCracken@chp.edu
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
LeeAnna Melton
Phone
615-343-6761
Email
leeanna.melton@vumc.org
Facility Name
John P. and Kathrine G. McGovern Medical School
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marilyn Garcia
Phone
713-500-5064
Email
marilyn.garcia@uth.tmc.edu
Facility Name
University of Utah Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kenzie Fait
Phone
801-585-7160
Email
kenzie.fait@hsc.utah.edu
Facility Name
Royal Children's Hospital Melbourne
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Beath Kara
Phone
+61 03 9345 6251
Email
kara.beath@mcri.edu.au
First Name & Middle Initial & Last Name & Degree
Jessica Yeo
Phone
+61 03 9345 6251
Email
jessica.yeo@mcri.edu.au
Facility Name
King Faisal Specialist Hospital and Research Centre
City
Riyadh
ZIP/Postal Code
11211
Country
Saudi Arabia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Asmaa Almrshad
Phone
+966 144 24988
Email
aalmrshad@kfshrc.edu.sa
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia
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