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

• Status: Completed
• Trial end date: 2018-11-15
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Human Genome Research Institute (NHGRI)
• Collaborator: National Center for Advancing Translational Science (NCATS)

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.