Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia

NCT04732429 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: HST20-CL01
• Study Type: interventional
• Target: 26
• Locations: 3 countries
• Sites: 16

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Change in plasma 2-methylcitric acid (MCA) levels

  nmol/mL

  6 months

Secondary Outcomes (13)

• Change in plasma propionyl-carnitine (3)

  6 months

• Change in C3 to acetyl-carnitine ratio (C3:C2)

  6 months

• Change in 3-OH propionate

  6 months

• Change in Methylmalonic acid (in MMA subjects)

  6 months

• Change in NH3

  6 months

Study Arms (2)

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).

Drug: HST5040

Placebo

EXPERIMENTAL

Placebo in addition to standard of care.

Drug: Placebo

Interventions

HST5040 DRUG

Liquid solution

Active Drug

Placebo DRUG

Liquid solution

Placebo

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• HemoShear Therapeutics: lead

Study Sites (16)

Rady Children's Hospital

San Diego, California, 92123, United States

Location

Yale

New Haven, Connecticut, 06520, United States

Location

Children's National Health System

Washington D.C., District of Columbia, 20010, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Children's Mercy Hospital Kansas City

Kansas City, Missouri, 64108, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

John P. and Kathrine G. McGovern Medical School

Houston, Texas, 77030, United States

Location

University of Utah Hospital

Salt Lake City, Utah, 84132, United States

Location

Royal Children's Hospital Melbourne

Parkville, Victoria, 3052, Australia

Location

King Faisal Specialist Hospital and Research Centre

Riyadh, Riyadh Region, 11211, Saudi Arabia

Location

MeSH Terms

Conditions

Methylmalonic acidemia; Propionic Acidemia; Metabolism, Inborn Errors; Metabolic Diseases; Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Amino Acid Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases

Study Officials

• Patrick Horn, MD PhD

  HemoShear Therapeutics, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2021
• First Posted: February 1, 2021
• Study Start: March 15, 2021
• Primary Completion: October 20, 2023
• Study Completion: October 20, 2023
• Last Updated: January 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

SA (1); US (14); AU (1)