Multi-Center Study of ManNAc for GNE Myopathy

NCT04231266 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: NN1091U01AR070498-01A1
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 10

Brief Summary

GNE myopathy is a rare genetic muscle disease characterized by progressive muscle atrophy and weakness. The disease is caused by mutations in the gene that encodes the enzyme that initiates and regulates N-acetylneuraminic acid (Neu5Ac) biosynthesis and glycan sialylation. Currently, there is no therapy available for this disease. N-Acetylmannosamine (ManNAc), an orphan drug in development for GNE myopathy, is an uncharged monosaccharide and the first committed precursor in Neu5Ac biosynthesis. In this randomized, double-blind, placebo-controlled trial the efficacy and long-term safety of ManNAc will be evaluated in subjects with GNE myopathy.

Conditions

GNE Myopathy

Keywords

GNE Myopathy; Hereditary Inclusion Body Myopathy (HIBM); Distal Myopathy with Rimmed Vacuoles (DMRV); Nonaka Myopathy; Inclusion Body Myopathy type 2 (IBM-2)

Outcome Measures

Primary Outcomes (1)

• Muscle strength of ankle dorsiflexion, knee flexion, knee extension, shoulder abduction, elbow flexion and grip measured by fixed-frame Quantitative Muscle Assessment (QMA)

  The primary endpoint is the change in muscle strength decline under treatment compared to placebo. The primary analysis is based on the disease progression ratio (γ) comparing the rate of progression from baseline until last visit, under placebo to that under treatment.

  Minimum 2 years, until 24 months from randomization of last subject

Secondary Outcomes (1)

• Inclusion Body Myositis Functional Rating Scale (IBMFRS)

  Minimum 2 years, until 24 months from randomization of last subject

Other Outcomes (10)

• Adverse Events

  Minimum 2 years, until 24 months from randomization of last subject

• Correlation muscle strength measured Exploratory GNEM Functional Questions (ExGNEM)

  Minimum 2 years, until 24 months from randomization of last subject

• Adult Myopathy Assessment Tool

  Minimum 2 years, until 24 months from randomization of last subject

Study Arms (2)

ManNAc

ACTIVE COMPARATOR

Oral ManNAc will be administered at a dose of 4 grams three times daily (total of 12 grams daily).

Drug: ManNAc

Placebo

PLACEBO COMPARATOR

Oral Placebo will be administered three times daily.

Other: Placebo

Interventions

ManNAc DRUG

Oral N-acetyl-D-mannosamine monohydrate (ManNAc)

Also known as: N-acetyl-D-mannosamine monohydrate

ManNAc

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Subject should be 18-70 years of age at the time of enrollment, inclusive, and of either gender.
• Subject has a diagnosis of GNE myopathy based upon a consistent clinical course and biallelic GNE gene mutations that classify as pathogenic or likely pathogenic according to American College of Medical Genetics and Genomics (ACMG) guidelines.
• Subjects must have 10.00-65.99% of predicted muscle strength measured by QMA at screening in at least one of the selected muscle groups (ankle dorsiflexion, knee flexion, grip, shoulder abduction and elbow flexion).
• Subject has the ability to travel to the Clinical Trial Site for visits.
• Subjects must be able to communicate effectively with study staff and understand the requirements of the protocol without translators.
• Subject must be able to comply with requirements of the protocol, including blood collection, drug administration, and muscle strength assessments.
• Women of childbearing potential must be willing to use an effective method of contraception for the duration of the trial. It is recommended that male subjects follow birth control measures for the duration of the trial.
• Subject must be able to provide informed consent.

You may not qualify if:

• Subject had an infection or medical illness requiring intravenous antibiotics or hospitalization within 30 days prior to the baseline/randomization visit.
• Subject has another comorbid condition which may affect physical function.
• Subject has a psychiatric illness or neurological disease that would interfere with the ability to comply with the requirements of this protocol.
• Subject with hepatic laboratory parameters (AST, ALT, GGTP), equal to or greater than 3 times the upper limit of normal at screening.
• Subject with existing renal dysfunction, as defined by glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2 at screening.
• Subject is anemic (defined as Hematocrit \<30%) or has platelets \<75 x 10\^3/µL or white blood cell count less than 3 x 10\^3/µL at screening.
• 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 screening.
• Subject has received any dose of ManNAc, sialic acid, intravenous immunoglobulin (IVIG), and/or other compounds containing, or that can be metabolized into sialic acid, within 6 months prior to enrollment as reported by subject at the time of screening.
• Subject has received stem cell therapy or gene therapy within 1 year prior to screening.
• Subject has hypersensitivity to ManNAc or erythritol or in the judgment of the investigator, has a condition that places the subject at increased risk for adverse effects.
• The presence of persistent diarrhea or malabsorption that could interfere with the subject's ability to absorb drugs or to tolerate ManNAc therapy.

Sponsors & Collaborators

• Leadiant Biosciences, Inc.: lead
• Brigham and Women's Hospital: collaborator
• National Human Genome Research Institute (NHGRI): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator
• NIH (NIAMS and NIND) as part of NeuroNext: collaborator

Study Sites (10)

UCLA

Los Angeles, California, 90095, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas, Medical Center

Kansas City, Kansas, 66160, United States

Location

NIH Clinical Center

Bethesda, Maryland, 20892, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Ohio State University, Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (3)

• Quintana M, Shrader J, Slota C, Joe G, McKew JC, Fitzgerald M, Gahl WA, Berry S, Carrillo N. Bayesian model of disease progression in GNE myopathy. Stat Med. 2019 Apr 15;38(8):1459-1474. doi: 10.1002/sim.8050. Epub 2018 Dec 3.

  PMID: 30511500 BACKGROUND

• Carrillo N, Malicdan MC, Huizing M. GNE Myopathy: Etiology, Diagnosis, and Therapeutic Challenges. Neurotherapeutics. 2018 Oct;15(4):900-914. doi: 10.1007/s13311-018-0671-y.

  PMID: 30338442 BACKGROUND

• Xu X, Wang AQ, Latham LL, Celeste F, Ciccone C, Malicdan MC, Goldspiel B, Terse P, Cradock J, Yang N, Yorke S, McKew JC, Gahl WA, Huizing M, Carrillo N. Safety, pharmacokinetics and sialic acid production after oral administration of N-acetylmannosamine (ManNAc) to subjects with GNE myopathy. Mol Genet Metab. 2017 Sep;122(1-2):126-134. doi: 10.1016/j.ymgme.2017.04.010. Epub 2017 Apr 26.

  PMID: 28641925 BACKGROUND

Related Links

• Study NN109/MAGiNE website

MeSH Terms

Conditions

Distal myopathy, Nonaka type

Interventions

N-acetylmannosamine

Study Officials

• Anthony A. Amato, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

• Francis Rossignol, MD

  National Institutes of Health (NIH)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2020
• First Posted: January 18, 2020
• Study Start: April 5, 2022
• Primary Completion: June 27, 2025
• Study Completion: October 30, 2025
• Last Updated: June 13, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)