ManNAc for GNE Myopathy

(MAGiNE Trial)

Recruiting at 9 trial locations

Overseen By Daniel Falleroni

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Leadiant Biosciences, Inc.

Must not be taking: ManNAc, Sialic acid, IVIG, others

Disqualifiers: Renal dysfunction, Anemia, Cardiovascular disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 9

Duration: 24 months

54 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests ManNAc, a sugar molecule, in patients with GNE myopathy, a rare muscle disease. The goal is to see if ManNAc can help produce more Neu5Ac, improving muscle strength and slowing down muscle weakening. ManNAc has been previously tested for safety in subjects with GNE myopathy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received certain treatments like ManNAc, sialic acid, or intravenous immunoglobulin (IVIG) within 6 months before joining the trial.

What data supports the effectiveness of the drug ManNAc for GNE myopathy?

Research shows that ManNAc, a drug being tested for GNE myopathy, helps increase levels of a substance called sialic acid in the body, which is important for muscle health. In studies, ManNAc was found to be safe and increased sialic acid levels in patients, suggesting it might help improve muscle function in this condition. ^{1 2 3 4 5}

Is ManNAc safe for humans?

ManNAc has been tested in humans with GNE myopathy and was generally safe and well tolerated at doses of 3 and 6 grams, though a 10-gram dose caused diarrhea. In animal studies, ManNAc showed acceptable safety for the kidneys and liver. ^{2 3 4 5 6}

How does the drug ManNAc differ from other treatments for GNE myopathy?

ManNAc is unique because it acts as a precursor to sialic acid, which is deficient in people with GNE myopathy due to a genetic enzyme deficiency. This approach aims to restore sialic acid levels in muscle tissues, addressing the root cause of the disease, unlike other treatments that may not target this specific biochemical pathway. ^{3 4 5 7 8}

Research Team

Anthony A Amato, MD

Principal Investigator

Brigham and Women's Hospital

Francis Rossignol, MD

Principal Investigator

National Institutes of Health (NIH)

Eligibility Criteria

This trial is for adults aged 18-70 with GNE myopathy, a muscle-weakening disease. Participants must have certain levels of muscle strength and be able to travel to the study site without assistance. Women who can get pregnant and men should use birth control during the trial. People with recent severe illness, other conditions affecting physical function, or those on certain medications recently cannot join.

Inclusion Criteria

Subject must be able to provide informed consent

My muscle strength in one of the specified areas falls within 10-66% of the expected level.

I can travel to the clinic for my appointments.

Exclusion Criteria

I have ongoing diarrhea or issues absorbing food that could affect my medication intake.

My kidney function is reduced, with a GFR under 60 mL/min.

I haven't used any experimental drugs or devices in the last 90 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Evaluation

Baseline evaluations including clinical laboratory tests, Quantitative Muscle Assessment (QMA), and other assessments

1 week

1 visit (in-person)

Treatment

Participants receive ManNAc or placebo for a minimum of 24 months

24 months

Follow-up visits every 6 months (in-person), monthly phone follow-ups

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

1 phone follow-up

Treatment Details

Interventions

• ManNAc
• Placebo

Trial Overview The study tests ManNAc, a drug in development for treating GNE myopathy against a placebo (a substance with no therapeutic effect). It's randomized and double-blind, meaning neither participants nor researchers know who gets the real drug versus placebo. The goal is to see if ManNAc improves muscle function safely over time.

Participant Groups

Group I: ManNAc Active Control 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

Oral Placebo will be administered three times daily.

Who Is Running the Clinical Trial?

Leadiant Biosciences, Inc.

Lead Sponsor

Trials

16

Recruited

940+

NIH (NIAMS and NIND) as part of NeuroNext

Collaborator

Trials

1

Recruited

50+

Brigham and Women's Hospital

Collaborator

Trials

1,694

Recruited

14,790,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Collaborator

Trials

508

Recruited

1,090,000+

National Human Genome Research Institute (NHGRI)

Collaborator

Trials

273

Recruited

299,000+

References

1. Germany pubmed.ncbi.nlm.nih.gov

Quantitative nuclear magnetic resonance imaging detects subclinical changes over 1 year in skeletal muscle of GNE myopathy. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics and sialic acid production after oral administration of N-acetylmannosamine (ManNAc) to subjects with GNE myopathy. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of N-acetylmannosamine (ManNAc) in patients with GNE myopathy: an open-label phase 2 study. [2022]

4. Singapore pubmed.ncbi.nlm.nih.gov

Evaluation of N-Acetylmannosamine Administration to Restore Sialylation in GNE-Deficient Human Embryonal Kidney Cells. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetic Model of N-acetylmannosamine (ManNAc) and N-acetylneuraminic acid (Neu5Ac) in Subjects with GNE Myopathy. [2021]

6. Japan pubmed.ncbi.nlm.nih.gov

[Animal model of distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy and preclinical trial with sugar compounds]. [2015]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Visualizing Muscle Sialic Acid Expression in the GNED207VTgGne-/- Cmah-/- Model of GNE Myopathy: A Comparison of Dietary and Gene Therapy Approaches. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Development of Assays to Measure GNE Gene Potency and Gene Replacement in Skeletal Muscle. [2023]