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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 : September 5, 2021
Sponsor:
Information provided by (Responsible Party):
HemoShear Therapeutics

Tracking Information
First Submitted Date  ICMJE January 21, 2021
First Posted Date  ICMJE February 1, 2021
Last Update Posted Date September 5, 2021
Actual Study Start Date  ICMJE March 15, 2021
Estimated Primary Completion Date January 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 2, 2021)
Change in plasma 2-methylcitric acid (MCA) levels [ Time Frame: 6 months ]
nmol/mL
Original Primary Outcome Measures  ICMJE
 (submitted: January 26, 2021)
Change in plasma 2-methylcitric acid (MCA) levels [ Time Frame: 12 months ]
nmol/mL
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2021)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: January 26, 2021)
  • Change in plasma propionyl-carnitine (3) [ Time Frame: 12 months ]
    µmol/L
  • Change in C3 to acetyl-carnitine ratio (C3:C2) [ Time Frame: 12 months ]
    µmol/L
  • Change in 3-OH propionate [ Time Frame: 12 months ]
    g/mol
  • Change in Methylmalonic acid (in MMA subjects) [ Time Frame: 12 months ]
    nmol/L
  • Change in NH3 [ Time Frame: 12 months ]
    nmol/L
  • Anion Gap [ Time Frame: 12 months ]
    mEq/L
  • Pharmacokinetics parameters - Cmax [ Time Frame: 12 months ]
    Maximum concentration (Cmax) after administration of HST5040
  • Pharmacokinetics parameters - Tmax [ Time Frame: 12 months ]
    Time of maximum concentration (Tmax)
  • Pharmacokinetics parameters - AUC [ Time Frame: 12 months ]
    Area under the concentration time curve (AUC)
  • Oral Intake [ Time Frame: 12 months ]
    Food diary - change from baseline to end of each dose level interval in oral intake
  • Acute Metabolic Decompensations [ Time Frame: 12 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: 12 months ]
    Score 0-100 Scale. Higher Score indicates better HRQOL
  • PedsQL 1.0 Family Impact Score - Health Related Quality of Life (HRQOL) [ Time Frame: 12 months ]
    Score 0-100 Scale. Higher Score indicates better HRQOL
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Methylmalonic Acidemia
  • Propionic Acidemia
Intervention  ICMJE
  • Drug: HST5040
    Liquid solution
  • Drug: Placebo
    Liquid solution
Study Arms  ICMJE
  • 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).
    Intervention: Drug: HST5040
  • Experimental: Placebo
    Placebo in addition to standard of care.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 26, 2021)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 31, 2026
Estimated Primary Completion Date January 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Confirmed diagnosis of symptomatic PA or MMA (Mutase)
  • Ages ≥ 2 years old.
  • Inadequate metabolic control while receiving standard of care (SoC) within the past 2 years
  • Plasma MCA concentration > 3x upper limit of normal of the reference range at screening.
  • Stable supplementation dose of carnitine for at least 3 months 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mavis Y Waller 833-975-3559 waller@hemoshear.com
Contact: Allison J Armstrong 833-975-3559 Armstrong@hemoshear.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04732429
Other Study ID Numbers  ICMJE HST20-CL01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party HemoShear Therapeutics
Study Sponsor  ICMJE HemoShear Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Gerald F Cox HemoShear Therapeutics, Inc.
PRS Account HemoShear Therapeutics
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP