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Protocol Details

A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Efficacy of ManNAc in Subjects with GNE Myopathy

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

20-HG-0025

Sponsoring Institute

National Human Genome Research Institute (NHGRI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18 Years
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

Children

Keywords

Hereditary Inclusion Body Myopathy (HIBM);
Nonaka Myopathy;
Orphan Drug;
Disease Progression Model;
Genetic Muscle Disease

Recruitment Keyword(s)

None

Condition(s)

GNE Myopathy

Investigational Drug(s)

ManNAc

Investigational Device(s)

None

Intervention(s)

Drug: ManNAc
Other: Placebo

Supporting Site

National Human Genome Research Institute

Background:

GNE myopathy is a rare disease that causes muscle wasting in adults. Symptoms include walking difficulties and muscle weakness that get worse the longer a person has the disease. Researchers want to see if a drug called ManNAc can help.

Objective:

To evaluate how well ManNAc works in reducing or slowing muscle weakness in people with GNE myopathy.

Eligibility:

Adults ages 18-70 who have GNE myopathy.

Design:

Participants will be screened with:

-Medical and medicine history

-Physical exam

-Mobility and stability tests

-Hand function test

-Tests of how well they perform common functional tasks

-Blood and urine tests

-Muscle strength tests of the lower legs and upper arms (for this, they will pull on an elastic band)

-Electrocardiogram (to check the heart s electrical function)

-Questionnaires about how they are functioning, their risk of falls, and how they feel emotionally.

Screening tests will be repeated during the study.

Participants will take the study drug or a placebo 3 times per day. They will take it by mouth, as a powder dissolved in water. They will be given an electronic diary to keep track of doses and symptoms.

Participants will have study visits at the NIH Clinical Center every 6 months. These visits will take up to 5-6 hours. They will have telephone follow-up visits every month between study visits. These calls will take about 10-15 minutes.

Participation lasts 26-38 months.

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Eligibility

INCLUSION CRITERIA:

1. Participant should be 18-70 years of age at the time of enrollment, inclusive, and of either gender.

2. Participant 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.

3. Participants 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, hand grip, shoulder abduction and elbow flexion).

4. Participant has the ability to travel to the Clinical Trial Site for visits.

5. Participants must be able to communicate effectively with study staff and understand the requirements of the protocol without translators.

6. Participant must be able to comply with requirements of the protocol, including blood collection, drug administration, and muscle strength assessments.

7. 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 Participants follow birth control measures for the duration of the trial.

8. Participant must be able to provide informed consent.

EXCLUSION CRITERIA:

1. Participant had an infection or medical illness requiring intravenous antibiotics or hospitalization within 30 days prior to the baseline/randomization visit.

2. Participant has another comorbid condition which may affect physical function.

3. Participant has a psychiatric illness or neurological disease that would interfere with the ability to comply with the requirements of this protocol.

4. Participant with hepatic laboratory parameters (AST, ALT, GGTP), equal to or greater than 3 times the upper limit of normal at screening.

5. Participant with existing renal dysfunction, as defined by estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m^2 at screening.

6. Participant is anemic (defined as Hematocrit <30%) or has platelets <75 x 10^3/microL or white blood cell count less than 3 x 10^3/microL at screening.

7. Participant shows evidence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, metabolic, or gastrointestinal disease, or has a condition that requires immediate surgical intervention.

8. Participant is pregnant or breastfeeding at any time during the study.

9. Participant has received treatment with another investigational drug, investigational device, or approved therapy for investigational use less than 90 days prior to screening.

10. Participant 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 Participant at the time of screening.

11. Participant has received stem cell therapy or gene therapy within 1 year prior to screening.

12. Participant has hypersensitivity to ManNAc or erythritol or in the judgment of the investigator, has a condition that places the Participant at increased risk for adverse effects.

13. The presence of persistent diarrhea or malabsorption that could interfere with the Participant's ability to absorb drugs or to tolerate ManNAc therapy.


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Citations:

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; PMCID: PMC6277305.

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; PMCID: PMC6277305.

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; PMCID: PMC5949875.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Francis Rossignol, M.D.
National Human Genome Research Institute (NHGRI)
NIHBC 10 - CLINICAL CENTER BG RM 10C103
10 CENTER DR
BETHESDA MD 20892
(301) 402-2324
francis.rossignol@nih.gov

Francis Rossignol, M.D.
National Human Genome Research Institute (NHGRI)
NIHBC 10 - CLINICAL CENTER BG RM 10C103
10 CENTER DR
BETHESDA MD 20892
(301) 402-2324
francis.rossignol@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1
ccopr@nih.gov

Clinical Trials Number:

NCT04231266

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