Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia

Phase 2TerminatedNCT04732429

HemoShear Therapeutics26 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Methylmalonic Acidemia Propionic Acidemia

Eligibility

Sex: ALLMin age: 2 Years

Medical Language ↔ Plain English

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.

Locations (16)

Rady Children's Hospital

San Diego, California, United States

Yale

New Haven, Connecticut, United States

Children's National Health System

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

Emory University School of Medicine

Atlanta, Georgia, United States

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

Chicago, Illinois, United States

Boston Children's Hospital

Boston, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

Children's Mercy Hospital Kansas City

Kansas City, Missouri, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

...and 6 more locations

Outcomes

Primary Outcomes

Change in plasma 2-methylcitric acid (MCA) levels

nmol/mL

Time frame: 6 months

Secondary Outcomes

Change in plasma propionyl-carnitine (3)

µmol/L

Time frame: 6 months

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

µmol/L

Time frame: 6 months

Change in 3-OH propionate

g/mol

Time frame: 6 months

Change in Methylmalonic acid (in MMA subjects)

nmol/L

Time frame: 6 months

Change in NH3

nmol/L

Time frame: 6 months

Anion Gap

mEq/L

Time frame: 6 months

Pharmacokinetics parameters - Cmax

Maximum concentration (Cmax) after administration of HST5040

Time frame: 6 months

Pharmacokinetics parameters - Tmax

Time of maximum concentration (Tmax)

Time frame: 6 months

Pharmacokinetics parameters - AUC

Area under the concentration time curve (AUC)

Time frame: 6 months

Oral Intake

Food diary - change from baseline to end of each dose level interval in oral intake

Time frame: 6 months

Acute Metabolic Decompensations

Change in the total number of metabolic decompensation events requiring an emergency room (ER) visit of hospitalization

Time frame: 6 months

MetabQoL 1.0 - Health Related Quality of Life (HRQOL)

Score 0-100 Scale. Higher Score indicates better HRQOL

Time frame: 6 months

PedsQL 1.0 Family Impact Score - Health Related Quality of Life (HRQOL)

Score 0-100 Scale. Higher Score indicates better HRQOL

Time frame: 6 months

Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia

Overview

Conditions

Interventions

Eligibility

Locations (16)

Outcomes

Primary Outcomes

Secondary Outcomes