An Open Label Phase 2 Study of ManNAc in Subjects With GNE Myopathy
Condition: GNE Myopathy
MeSH terms: Muscular Diseases; Distal Myopathies
Intervention: ManNAc; ManNAc
Intervention description: At doses of 3 g and 6 g twice daily for a total dose of 6 and 12 g per day.; At doses of 6 g twice daily (12 g per day).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Hereditary Inclusion Body Myopathy (HIBM); Sialic Acid (N-acetylneuraminic acid, Neu5Ac); GNE Myopathy; N-Acetyl-D-mannosamine (ManNAc); GNE Gene

Summary:

      Background:

      Patients with GNE myopathy have progressive muscle weakness and can have difficulty walking
      and decreased mobility. The disease is a rare genetic disorder that results from a gene
      mutation in a key step in the body's production of a sugar called sialic acid, (also called
      N-acetylneuraminic acid, Neu5Ac). Researchers think decreased sialic acid bound to muscle
      proteins may be the cause of muscle wasting in GNE myopathy. Researchers are testing the drug
      ManNAc which is a precursor in the production of sialic acid within cells. ManNAc is provided
      as a powder dissolved in water to be administered orally.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Subject is age 18-60 years, inclusive, and of either gender.

          -  Subject has a diagnosis of GNE myopathy based upon a consistent clinical course and
             identification of two GNE gene mutations.

          -  Subject must be willing to stop any treatment with ManNAc, sialic acid, intravenous
             immunoglobulin (IVIG), and/or other supplements containing sialic acid (e.g. St. John
             s wort, sialyllactose) 90 days prior to dosing and remain off such treatment for the
             duration of the trial.

          -  Subjects must have a body mass index (BMI) between 18 and 30 kg/m2, with a bodyweight
             of >50 kg.

          -  Subjects must have 20-75% of predicted strength measured by QMA at baseline on at
             least one of the following: 1) ankle dorsiflexion, 2) knee flexion, 3) hip extension,
             4) grip, 5) elbow flexion, shoulder abduction

               -  20-75% of predicted strength measures by OMA at baseline, or

               -  If predicted muscle strength above 75%, a documented change of at least 10% per
                  year.

          -  Subject has the ability to travel to the NIH Clinical Center for admissions.

          -  Subject has an INR less than or equal to 1.5 and must have stopped warfarin and other
             anticoagulants 2 weeks prior and after muscle biopsy procedures. Aspirin and
             clopidogrel should be stopped 3 days and 5 days before the procedure, respectively.

          -  Subject must be able to comply with requirements of the protocol, including blood
             collection, drug administration, muscle MRI/MRS, muscle biopsy and muscle strength
             assessments.

          -  If a woman of reproductive age, subject must be willing to use an effective method of
             contraception for the duration of the trial.

          -  Subject must be able to provide informed consent.

        EXCLUSION CRITERIA:

          -  Subject had a clinical significant infection or medical illness 30 days prior to the
             first protocol visit.

          -  Subject has a psychiatric illness or neurological disease that would interfere with
             the ability to comply with the requirements of this protocol. This includes, but is
             not limited to, uncontrolled/untreated psychotic depression, bipolar disorder,
             schizophrenia, substance abuse or dependence, antisocial personality disorder, panic
             disorder, or behavioral problems, which interfere with effective communication.

          -  Subject has hepatic laboratory parameters (AST, ALT, GGTP) or renal laboratory
             parameters (creatinine, BUN) greater than 3 times the upper limit of normal.

          -  Subject has known adverse reactions to anesthetic or sedatives utilized for muscle
             biopsy.

          -  Subject is anemic (defined as Hematocrit <30%) or has platelets <100,000 or white
             blood cell count less than 3,000.

          -  Subject shows evidence of clinically significant cardiovascular, pulmonary, hepatic,
             renal, hematological, metabolic, or gastrointestinal disease, or has a condition that
             requires immediate surgical intervention.

          -  Subject is pregnant or breastfeeding at any time during the study.

          -  Subject has received treatment with another investigational drug, investigational
             device, or approved therapy for investigational use less than 90 days prior to the
             first protocol visit.

          -  Subject has hypersensitivity to ManNAc or in the judgment of the investigator, has a
             condition that places the subject at increased risk for adverse effects.

          -  Subject has received ManNAc, sialic acid, intravenous immunoglobulin (IVIG), and/or
             other supplements containing sialic acid (e.g. St. John s wort, sialyllactose) less
             than 90 days prior to the first protocol visit.

          -  The presence of persistent diarrhea or malabsorption that could interfere with the
             subject s ability to absorb drugs or to tolerate ManNAc therapy.