Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia

Brief Title

Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia

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

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.
    


Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Change in plasma 2-methylcitric acid (MCA) levels

Secondary Outcome

 Change in plasma propionyl-carnitine (3)

Condition

Methylmalonic Acidemia

Intervention

HST5040

Study Arms / Comparison Groups

 Active Drug
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).

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

12

Start Date

March 15, 2021

Completion Date

January 31, 2026

Primary Completion Date

January 31, 2023

Eligibility Criteria

        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 4
             years.

          -  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.
      

Gender

All

Ages

2 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Gerald F Cox, 833-975-3559, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04732429

Organization ID

HST20-CL01


Responsible Party

Sponsor

Study Sponsor

HemoShear Therapeutics


Study Sponsor

Gerald F Cox, Study Chair, HemoShear Therapeutics, Inc.


Verification Date

October 2021