Expired Study
This study is not currently recruiting Study Participants on ClinicalConnection.com. If you would like to find active studies please search for clinical trials.

Bethesda, Maryland 20892


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 take the study drug at home. Participants will need to record if they miss any doses. - Visit 2 will be at 6 weeks for 1 2 days of medical evaluation. Blood samples will be drawn. - Visit 3 will be at the end of the study. Participants will stay in the NIH Clinical Center for 5 6 days for medical evaluations, muscle tests, and scans. Another muscle biopsy will be taken. Blood samples will be drawn. - Participants will be contacted by telephone or email about 4 times after leaving the clinic.

Study 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 evaluations will occur at 42 days, and at 91 (3 months), 182 (6 months), 365 (12 months), 548 (18 months), 730 (24 months) and 912 (30 months) days. Safety lab evaluation will be performed also at 456 (15 months), 638 (21 months) and 820 (27 months) days either at the NIH clinical center or subjects home laboratory or physician s office. Final dosing will occur at the 30-month visit. After the final dose, all Grade (Bullet)2 AEs at least possibly related to study drug will be followed to resolution. Safety will be evaluated by adverse events (AEs), clinical laboratory tests, vital signs, and physical examinations. PK will be assessed for plasma ManNAc and Neu5Ac. Biochemical efficacy will be measured by change in the sialylation of proteins and clinical efficacy will be assessed using a battery of clinical assessments deemed to be relevant based on disease natural history.


- 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 DEX-M74/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.



Primary Contact:

Principal Investigator
Nuria Carrillo-Carrasco, M.D.
National Human Genome Research Institute (NHGRI)

Backup Contact:


Location Contact:

Bethesda, Maryland 20892
United States

There is no listed contact information for this specific location.

Site Status: N/A

Data Source: ClinicalTrials.gov

Date Processed: March 16, 2018

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.

Click to view Full Listing

This study is not currently recruiting Study Participants on ClinicalConnection.com. The form below is not enabled.