Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia

NCT ID: NCT04732429

Last Updated: 2024-01-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-15

Study Completion Date

2023-10-20

Brief Summary

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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.

Detailed Description

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Conditions

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Methylmalonic Acidemia Propionic Acidemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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).

Group Type EXPERIMENTAL

HST5040

Intervention Type DRUG

Liquid solution

Placebo

Placebo in addition to standard of care.

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

Liquid solution

Interventions

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HST5040

Liquid solution

Intervention Type DRUG

Placebo

Liquid solution

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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HemoShear Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Patrick Horn, MD PhD

Role: STUDY_CHAIR

HemoShear Therapeutics, Inc.

Locations

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Rady Children's Hospital

San Diego, California, United States

Site Status

Yale

New Haven, Connecticut, United States

Site Status

Children's National Health System

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

Site Status

Emory University School of Medicine

Atlanta, Georgia, United States

Site Status

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

Chicago, Illinois, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Children's Mercy Hospital Kansas City

Kansas City, Missouri, United States

Site Status

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

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

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

John P. and Kathrine G. McGovern Medical School

Houston, Texas, United States

Site Status

University of Utah Hospital

Salt Lake City, Utah, United States

Site Status

Royal Children's Hospital Melbourne

Parkville, Victoria, Australia

Site Status

King Faisal Specialist Hospital and Research Centre

Riyadh, Riyadh Region, Saudi Arabia

Site Status

Countries

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United States Australia Saudi Arabia

Other Identifiers

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HST20-CL01

Identifier Type: -

Identifier Source: org_study_id

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