ManNAc for GNE Myopathy

(MAGiNE Trial)

Recruiting at 10 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ManNAc for individuals with GNE myopathy, a rare genetic disease that gradually weakens muscles. Researchers aim to determine if ManNAc can safely improve or slow muscle deterioration in affected individuals. Participants will receive either ManNAc or a placebo (a pill with no active medicine) to compare outcomes. This trial may suit those with GNE myopathy confirmed by genetic testing who experience progressive muscle weakness and can travel for study visits. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in treatment.

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.

Is there any evidence suggesting that ManNAc is likely to be safe for humans?

Research has shown that ManNAc has been tested in people and appears safe. In one study, patients with GNE myopathy took ManNAc orally, and it was well-tolerated without serious side effects. Another study found that a single dose of up to 6 grams of ManNAc was safe and increased sialic acid levels in the body, which is important for treating GNE myopathy. These findings suggest that ManNAc is generally safe for people, although further testing continues to confirm these results. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for GNE Myopathy, which typically focus on supportive care and symptomatic relief, ManNAc offers a new approach by supplying the body with a precursor to sialic acid, which is deficient in individuals with this condition. This treatment is unique because it targets the underlying biochemical deficiency, potentially slowing disease progression rather than just managing symptoms. Researchers are excited about ManNAc because it directly addresses the root cause of the muscle weakness in GNE Myopathy, offering hope for more effective management of this rare genetic disorder.

What evidence suggests that ManNAc might be an effective treatment for GNE myopathy?

Research has shown that ManNAc, which participants in this trial may receive, might help treat GNE myopathy, a rare muscle disease that causes gradual weakness. Previous studies found that ManNAc slowed the disease's progression over 12 to 18 months. It provides a key component for Neu5Ac, a molecule important for muscle health. ManNAc has proven safe for long-term use and has shown effects consistent with its intended purpose. While clinical testing continues, these early results offer promise for those affected by GNE myopathy. ^{2 6 7 8 9}

Who Is on the Research Team?

Anthony A Amato, MD

Principal Investigator

Brigham and Women's Hospital

Francis Rossignol, MD

Principal Investigator

National Institutes of Health (NIH)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. nature.com nature.com/articles/s41436-021-01259-x

Safety and efficacy of N-acetylmannosamine (ManNAc) in ... ManNAc showed long-term safety, biochemical efficacy consistent with the intended mechanism of action, and preliminary evidence clinical efficacy in patients ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01634750

Phase I Clinical Trial of ManNAc in Patients With GNE ... Researchers are studying a drug called ManNAc. It may be useful for treating HIBM. However, this drug is still being tested.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34257421/

Safety and efficacy of N-acetylmannosamine (ManNAc) in ... Decreased disease progression was estimated at 12 (γ = 0.61 [95% CI: 0.09, 1.27]) and 18 months (γ = 0.55 [95% CI: 0.12, 1.02]) using the GNE- ...

4. ucla.clinicaltrials.researcherprofiles.org ucla.clinicaltrials.researcherprofiles.org/trial/NCT04231266

ManNAc for GNE Myopathy - Clinical Trials at UCLA 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 ...

5. genome.gov genome.gov/Current-NHGRI-Clinical-Studies/GNE-Myopathy

GNE Myopathy The study collects genetic and medical information from people with GNE myopathy to understand the symptoms and clinical course of GNE ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8553608/

Safety and efficacy of N-acetylmannosamine (ManNAc) in ... We conducted an open-label, phase 2, single-center (NIH, USA) study to evaluate oral ManNAc in 12 patients with GNE myopathy.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S109671921730152X

Safety, pharmacokinetics and sialic acid production after ... A single dose of up to 6 g of oral ManNAc is safe and well tolerated. Oral administration of ManNAc significantly increases circulating levels of sialic acid ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02346461

An Open Label Phase 2 Study of ManNAc in Subjects With ... INCLUSION CRITERIA: Subject is age 18-60 years, inclusive, and of either gender. Subject has a diagnosis of GNE myopathy based upon a consistent clinical course ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5949875/

Safety, pharmacokinetics and sialic acid production after ... GNE myopathy is a rare, autosomal recessive, inborn error of sialic acid metabolism, caused by mutations in GNE, the gene encoding ...