Phase I Clinical Trial of ManNAc in Patients With GNE Myopathy or Hereditary Inclusion Body Myopathy (HIBM)

NCT01634750 | Completed Phase 1

• 2 other identifiers: 12020712-HG-0207
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Hereditary inclusion body myopathy (HIBM) is a genetic disorder caused by mutations in a gene called GNE. This gene is responsible for producing a sugar called sialic acid. Low levels of sialic acid may cause muscle problems. Symptoms of HIBM include walking difficulties and muscle weakness, which usually start in a person s 20s or 30s and become worse over time. Researchers are studying a drug called ManNAc. It may be useful for treating HIBM. However, this drug is still being tested. Researchers want to see how ManNAc is absorbed into and removed from the blood. They will not be looking specifically at whether ManNAc can stop or slow the symptoms of HIBM. Objectives:

• \<TAB\>To study how MaNAc is absorbed into and removed from the blood in people with HIBM.
• \<TAB\>To study of safety of ManNAc in people with HIBM. Eligibility: \- Individuals between 18 and 70 years of age who have HIBM. Design:
• Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
• Participants will have a 3 to 4-day inpatient stay for the main part of the study.
• Participants will be divided into groups of six. In each group, four will take ManNAc and two will take a placebo. Participants will not know which one they will receive.
• Participants will have a single dose of either ManNAc or placebo. They will be monitored for any possible side effects. Frequent blood samples will be collected during the 4-day stay.
• No treatment for HIBM will be provided as part of this study.

Conditions

Hereditary Inclusion Body Myopathy (HIBM); GNE Myopathy

Keywords

N-Acetyl-D-mannosamine (ManNAc); HIBM; GNE Myopathy

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety and tolerability of a single dose of orally administered ManNAc to HIBM subjects.

Secondary Outcomes (1)

• Pharmacokinetics

Study Arms (2)

ManNac

EXPERIMENTAL

Drug: ManNAc

Placebo

PLACEBO COMPARATOR

Drug: ManNAc

Interventions

ManNAc DRUG

Single dose

ManNac; Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Subject has a severe disease manifestation that would interfere with the ability to comply with the requirements of this protocol.
• 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, or panic disorder.
• 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 a QTcB \>450 msec (males) or QTcB \>470 msec (females).
• Subject is anemic (defined as two standard deviations below normal for age and gender).
• 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 within 4 weeks of initial screening.
• Subject has a hypersensitivity to ManNAc or in the judgment of the investigator, has a condition that places the subject at increased risk for adverse effects.

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI): lead
• National Center for Advancing Translational Sciences (NCATS): collaborator
• Therapeutics for Rare and Neglected Diseases (TRND): collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Amir SM, Barker SA, Butt WR, Crooke AC, Davies AG. Administration of N-acetyl-D-mannosamine to mammals. Nature. 1966 Aug 27;211(5052):976-7. doi: 10.1038/211976a0. No abstract available.

  PMID: 5970419 BACKGROUND

• Argov Z, Mitrani-Rosenbaum S. The hereditary inclusion body myopathy enigma and its future therapy. Neurotherapeutics. 2008 Oct;5(4):633-7. doi: 10.1016/j.nurt.2008.07.004.

  PMID: 19019317 BACKGROUND

• Bork K, Reutter W, Gerardy-Schahn R, Horstkorte R. The intracellular concentration of sialic acid regulates the polysialylation of the neural cell adhesion molecule. FEBS Lett. 2005 Sep 12;579(22):5079-83. doi: 10.1016/j.febslet.2005.08.013.

  PMID: 16137682 BACKGROUND

• Van Wart S, Mager DE, Bednasz CJ, Huizing M, Carrillo N. Population Pharmacokinetic Model of N-acetylmannosamine (ManNAc) and N-acetylneuraminic acid (Neu5Ac) in Subjects with GNE Myopathy. Drugs R D. 2021 Jun;21(2):189-202. doi: 10.1007/s40268-021-00343-6. Epub 2021 Apr 24.

  PMID: 33893973 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Distal myopathy, Nonaka type

Interventions

N-acetylmannosamine

Study Officials

• Nuria Carrillo-Carrasco, M.D.

  National Human Genome Research Institute (NHGRI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2012
• First Posted: July 6, 2012
• Study Start: September 11, 2012
• Study Completion: May 29, 2013
• Last Updated: October 19, 2017

Record last verified: 2017-02-24

Locations

US (1)