Clinical Trial: An Open Label Phase 2 Study of ManNAc in Subjects With GNE Myopathy

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: An Open-Label Phase 2 Study of ManNAc in Subjects With GNE Myopathy

Brief Summary:

Background:

- People with GNE myopathy have muscle weakness and can have difficulty walking . The disease comes from a gene mutation related to the production of a sugar called sialic acid. Researchers think decreased sialic acid may cause the muscle problems. Researchers are testing the drug ManNAc which is a building block of sialic acid. It is a powder that is dissolved in water.

Objective:

- To evaluate the safety of 90 days of ManNAc given by mouth.

Eligibility:

- Adults ages 18 60 diagnosed with GNE myopathy.

Design:

  • Eligible participants will be admitted to the NIH Clinical Center for the first visit and will stay 10 14 days. Participants will have:
  • Medical history and physical exam
  • Electrocardiogram to measure heart function
  • Blood and urine tests
  • Muscle strength tests
  • Magnetic resonance imaging (MRI) muscle scans. Participants will lie on a table that slides in and out of a metal tube that takes pictures
  • Questionnaires
  • Muscle biopsies. Samples of muscle will be taken, one each from the arm and leg.
  • The study drug as a liquid twice a day
  • Participants may wear a small activity monitor throughout the study. It can be worn on a waistband.
  • After discharge from the initial visit, participants will tak

    Detailed Summary: GNE myopathy, previously known as hereditary inclusion body myopathy (HIBM), is a rare, autosomal recessive myopathy with onset in early adulthood that is characterized by progressive muscle weakness and atrophy, which leads to wheelchair use and dependent care. The causative gene, GNE, encodes the rate-limiting enzyme in the biosynthesis of sialic acid. While the exact pathophysiology of GNE myopathy remains unknown, decreased sialic acid production and subsequent hyposialylation of muscle glycoproteins are thought to be key factors leading to muscle deterioration in GNE myopathy. This hypothesis is supported by prevention of disease after administration of N-acetyl-D-mannosamine (ManNAc) in mouse models of GNE myopathy. A recent first-in-human, Phase 1 single ascending dose study evaluated the safety, pharmacokinetics, and pharmacodynamics of a single dose of 3,000, 6,000, or 10,000 mg drug product-grade ManNAc in subjects with GNE myopathy (ClinicalTrials.gov NCT01634750; IND No.78,091). ManNAc was safe and well-tolerated in all subjects who participated in this study. In this Phase 2, open-label, single-center study we propose to administer ManNAc orally to 12 subjects for 912 days (30 months). The objectives of the study are to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and biochemical efficacy of orally administered ManNAc in GNE myopathy subjects and to evaluate disease-related biomarkers and relevant clinical endpoints. In the first phase of pharmacokinetic assessment, two cohorts of 6 subjects will receive ManNAc at doses of 3,000 mg twice a day (6,000 mg per day) or 6,000 mg twice a day (12,000 mg per day) for 7 days while admitted to the NIH Clinical Center to assess PK and safety. Safety and tolerability will be assessed on an individual basis. In the second phase of the study, all subjects will receive treatment with ManNAc at a dose of 6,000 mg twice daily for the remainder of the study. Follow-up safety and efficacy evaluation
    Sponsor: National Human Genome Research Institute (NHGRI)

    Current Primary Outcome:

    • Safety [ Time Frame: Day 1-120 ]
    • Pharmacokinetics and Pharmacodynamics [ Time Frame: Baseline, Day 1-93 ]
    • Biochemical efficacy [ Time Frame: Baseline, Day 1-93 ]


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    Original Secondary Outcome:

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: January 24, 2015
    Date Started: January 14, 2015
    Date Completion: August 30, 2018
    Last Updated: May 12, 2017
    Last Verified: February 28, 2017