Multi-Center Study of ManNAc for GNE Myopathy (MAGiNE)
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ClinicalTrials.gov Identifier: NCT04231266 |
Recruitment Status :
Recruiting
First Posted : January 18, 2020
Last Update Posted : March 27, 2023
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Condition or disease | Intervention/treatment | Phase |
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GNE Myopathy | Drug: ManNAc Other: Placebo | Phase 2 |
This is a randomized, placebo-controlled, double-blind, multi-center study to evaluate the long-term safety and clinical efficacy of ManNAc in subjects with GNE myopathy.
A total of 51 eligible subjects will be randomized in a 2:1 ratio to receive either ManNAc at 4 g three times daily (total of 12 g/day) or placebo. Subjects will have follow-up visits every 6 months (±7 days) and take study drug for a minimum of 24 months, until their final study visit . The final on-site study visit for a subject is the last expected 6-month follow-up visit that occurs prior to the time the last randomized subject is expected to reach 24 months (extended follow-up).
Subjects will undergo screening and baseline evaluations that include clinical laboratory tests, Quantitative Muscle Assessment (QMA), the Inclusion Body Functional Myositis Rating Scale (IBMFRS), and other patient-reported outcomes (PROs), and rehabilitation medicine functional assessments. Follow-up evaluations will occur every six months following baseline, until 24 months after randomization of the last subject. Phone follow-up will occur every month without a clinic visit for the duration of the trial, and the last visit for each subject will be followed by phone follow-up 1 month after the final study visit.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 51 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Efficacy of ManNAc in Subjects With GNE Myopathy |
Actual Study Start Date : | April 5, 2022 |
Estimated Primary Completion Date : | March 28, 2024 |
Estimated Study Completion Date : | July 15, 2024 |

Arm | Intervention/treatment |
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Active Comparator: ManNAc
Oral ManNAc will be administered at a dose of 4 grams three times daily (total of 12 grams daily).
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Drug: ManNAc
Oral N-acetyl-D-mannosamine monohydrate (ManNAc)
Other Name: N-acetyl-D-mannosamine monohydrate |
Placebo Comparator: Placebo
Oral Placebo will be administered three times daily.
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Other: Placebo
Placebo |
- Muscle strength of ankle dorsiflexion, knee flexion, knee extension, shoulder abduction, elbow flexion and grip measured by fixed-frame Quantitative Muscle Assessment (QMA) [ Time Frame: Minimum 2 years, until 24 months from randomization of last subject ]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.
- Inclusion Body Myositis Functional Rating Scale (IBMFRS) [ Time Frame: Minimum 2 years, until 24 months from randomization of last subject ]Change in patient-reported function as measured by the Inclusion Body Myositis Functional Rating Scale (IBMFRS).
- Adverse Events [ Time Frame: Minimum 2 years, until 24 months from randomization of last subject ]Safety and tolerability will be evaluated by comparing the frequency of adverse events (AEs) across groups, collected using information from in-person assessments, clinical laboratory tests, vital signs, electronic diary reports, and physical examinations.
- Correlation muscle strength measured Exploratory GNEM Functional Questions (ExGNEM) [ Time Frame: Minimum 2 years, until 24 months from randomization of last subject ]Evaluate the effect of ManNAc on patient-reported physical functioning assessed by ExGNEM, a six-question rating scale that assesses lower body function.
- Adult Myopathy Assessment Tool [ Time Frame: Minimum 2 years, until 24 months from randomization of last subject ]Evaluate the effect of ManNAc on physical function as measured by the Adult Myopathy Assessment Tool (AMAT), a 13-item standardized test that assesses physical performance, to be performed at baseline and every 6 months thereafter until completion of the study.
- Six-Minute Walk Test [ Time Frame: Minimum 2 years, until 24 months from randomization of last subject ]Evaluate the effect of ManNAc on physical function as measured by the Six-Minute Walk Test (whenever possible) to be performed at baseline and every 6 months thereafter until completion of the study.
- Timed Up and Go Test [ Time Frame: Minimum 2 years, until 24 months from randomization of last subject ]Evaluate the effect of ManNAc on physical function as measured by the Timed Up and Go, performance test to evaluate functional mobility, to be performed at baseline and every 6 months thereafter until completion of the study.
- Functional Reach Test [ Time Frame: Minimum 2 years, until 24 months from randomization of last subject ]Evaluate the effect of ManNAc on physical function as measured by the Functional Reach, a measure of stability, to be performed at baseline and every 6 months thereafter until completion of the study.
- Jebsen Hand Function Test [ Time Frame: Baseline and every 12 months thereafter ]Evaluate the effect of ManNAc on physical function as measured by the Jebsen Hand Function Test, a performance measure which assesses unilateral hand function, to be performed at baseline and every 6 months thereafter until completion of the study.
- Inclusion Body Myositis Functional Rating Scale [ Time Frame: Minimum 2 years, until 24 months from randomization of last subject ]Evaluate effect of ManNAc on activities of daily living (ADLs) compared to placebo as measured by the Inclusion Body Myositis Functional Rating Scale (IBMFRS), a patient-reported outcome completed at baseline, and every 6 months thereafter until completion of the study.
- Human Activity Profile [ Time Frame: Minimum 2 years, until 24 months from randomization of last subject ]Evaluate effect of ManNAc on activities of daily living (ADLs) compared to placebo as measured by the Human Activity Profile, a patient-reported outcome completed at baseline, and every 6 months thereafter until completion of the study.
- Activities-specific Balance Confidence (ABC) scale [ Time Frame: Minimum 2 years, until 24 months from randomization of last subject ]Evaluate effect of ManNAc on activities of daily living (ADLs) compared to placebo as measured by the Activities-specific Balance Confidence (ABC) scale, a patient-reported outcome completed at baseline, and every 6 months thereafter until completion of the study.

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Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04231266
Contact: Anthony A Amato, MD | 617-732-8046 | aamato@bwh.harvard.edu | |
Contact: Daniel Falleroni | 1-800-447-0169 | daniel.falleroni@leadiant.com |
United States, California | |
UCLA | Recruiting |
Los Angeles, California, United States, 90095 | |
Contact: Merve Kaleli 310-825-3264 MKaleli@mednet.ucla.edu | |
Contact: Perry B Shieh, MD, PhD | |
Principal Investigator: Perry B Shieh, MD, PhD | |
United States, Iowa | |
University of Iowa | Recruiting |
Iowa City, Iowa, United States, 52242 | |
Contact: Loraine Brenner 319-356-8744 loraine-brenner@uiowa.edu | |
Principal Investigator: Chris Nance, MD | |
United States, Kansas | |
University of Kansas, Medical Center | Recruiting |
Kansas City, Kansas, United States, 66160 | |
Contact: Lilli Saavedra 913-945-9937 lsaavedra2@kumc.edu | |
Principal Investigator: Duaa Jabari, MD | |
United States, Maryland | |
NIH Clinical Center | Recruiting |
Bethesda, Maryland, United States, 20892 | |
Contact: Jessica Jang, NP 301-827-7746 GNEMyopathyStudies@mail.nih.gov | |
Principal Investigator: Francis Rossignol, MD | |
United States, Massachusetts | |
Brigham and Women's Hospital | Recruiting |
Boston, Massachusetts, United States, 02115 | |
Contact: Kylie Yamauchi 808-393-5379 kcyamauchi@bwh.harvard.edu | |
Contact: Louis Beers | |
Principal Investigator: Anthony A Amato, MD | |
United States, Missouri | |
Washington University | Recruiting |
Saint Louis, Missouri, United States, 63110 | |
Contact: Mengesha Teshome 314-747-8420 teshomem@wustl.edu | |
Principal Investigator: Alan Pestronk, MD | |
United States, New York | |
Columbia University Medical Center | Recruiting |
New York, New York, United States, 10032 | |
Contact: Joyce Moran 212-305-8367 jt617@cumc.columbia.edu | |
Principal Investigator: Jinsy Andrews, MD | |
University of Rochester | Recruiting |
Rochester, New York, United States, 14642 | |
Contact: Erin Richardson 585-275-7867 erin_richardson@urmc.rochester.edu | |
Principal Investigator: Johanna Hamel, MD | |
United States, Ohio | |
Ohio State University, Wexner Medical Center | Recruiting |
Columbus, Ohio, United States, 43210 | |
Contact: Marco Tellez 614-366-9050 marco.tellez@osumc.edu | |
Principal Investigator: Michael Isfort, MD | |
United States, Utah | |
University of Utah | Recruiting |
Salt Lake City, Utah, United States, 84112 | |
Contact: Mariana Doudova 801-581-3818 mariana.doudova@hsc.utah.edu | |
Principal Investigator: J. Robinson Singleton, MD |
Principal Investigator: | Anthony A. Amato, MD | Brigham and Women's Hospital |
Publications:
Responsible Party: | Leadiant Biosciences, Inc. |
ClinicalTrials.gov Identifier: | NCT04231266 |
Other Study ID Numbers: |
NN109 1U01AR070498-01A1 ( U.S. NIH Grant/Contract ) |
First Posted: | January 18, 2020 Key Record Dates |
Last Update Posted: | March 27, 2023 |
Last Verified: | March 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
GNE Myopathy Hereditary Inclusion Body Myopathy (HIBM) Distal Myopathy with Rimmed Vacuoles (DMRV) Nonaka Myopathy Inclusion Body Myopathy type 2 (IBM-2) |
Muscular Diseases Distal Myopathies Musculoskeletal Diseases Neuromuscular Diseases |
Nervous System Diseases Muscular Dystrophies Muscular Disorders, Atrophic Genetic Diseases, Inborn |