GlcNAc for NGLY1 Deficiency

Not currently recruiting at 2 trial locations

Overseen By Mary Freeman, MS, CGC

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Eva Morava-Kozicz

Disqualifiers: Shellfish allergy, Pregnancy, others

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

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial targets individuals with NGLY1 deficiency, a rare disorder that can cause dry eyes due to low tear production. Researchers are testing a dietary supplement called GlcNAc (GlcNAc-GlcN) to determine if it can enhance tear production. Participants will receive either the GlcNAc supplement or a placebo, a harmless pill resembling the treatment but lacking active ingredients, to compare outcomes. This trial suits those diagnosed with NGLY1 deficiency who experience dry eyes. As a Phase 2 trial, the research aims to measure the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you cannot have taken GlcNAc within 28 days before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that GlcNAc (N-acetylglucosamine) is under investigation for its safety and effectiveness in treating NGLY1 deficiency. This condition can impair tear production, leading to eye damage. While specific data on using GlcNAc for this condition is lacking, it is a dietary supplement commonly used for other purposes and is generally well-tolerated.

The study is in Phase 2, indicating some early evidence of safety from previous testing. In this phase, researchers focus on how the treatment works in people and continue to monitor its safety. Side effects may occur, but they are usually mild and manageable. Prospective participants should discuss potential risks with the study team before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike other treatments for NGLY1 deficiency, which are mostly supportive and focus on managing symptoms, GlcNAc-GlcN is unique because it targets the underlying biochemical pathway affected by the condition. Researchers are excited about this treatment because it introduces N-Acetylglucosamine (GlcNAc) as a potential therapy that may influence protein deglycosylation, a process disrupted in NGLY1 deficiency. This approach could offer a more targeted treatment option, potentially improving outcomes by addressing the root cause of the disorder rather than just alleviating symptoms.

What evidence suggests that GlcNAc might be an effective treatment for NGLY1 deficiency?

This trial will compare GlcNAc (N-acetylglucosamine) with a placebo to determine whether GlcNAc can help treat NGLY1 deficiency, a condition that reduces tear production and harms the eyes. GlcNAc plays a crucial role in this condition as a key molecule involved. The research aims to discover if GlcNAc can increase tear production, potentially benefiting those with the deficiency. While direct evidence of its effectiveness for tear production is still being gathered, the connection between GlcNAc and the condition suggests potential benefits. Early studies focus on confirming this possible advantage. ^{4 6 7 8 9}

Who Is on the Research Team?

Eva Morava-Kozicz, MD, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for individuals with NGLY1-CDDG, a condition that impairs tear production and can damage the eyes. Participants must have a confirmed diagnosis, be willing to consent (or have a guardian who can consent), and not be planning eye surgery soon or participating in other drug trials.

Inclusion Criteria

My condition is confirmed to be NGLY1-CDDG.

Willingness of subject or legal guardian to provide consent

Parent or legal guardian available to provide consent on behalf of minor subjects or adult subjects who are unable to give informed consent due to developmental disabilities

Exclusion Criteria

You are allergic to any of the ingredients in the placebo.

I am scheduled for eye surgery within the next 3 months.

Participation in another therapeutic trial - the subject will not be permitted to participate in any other drug trial during the blinded phase and during the 28 days prior to Visit 1

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Washout

Participants already on GlcNAc undergo a washout period before consent and randomization

4 weeks

Treatment

Participants receive weight-dependent doses of GlcNAc or placebo for 6 weeks

6 weeks

1 visit (in-person) at 6 weeks

Open-label Treatment

Participants receive open-label weight-dependent doses of GlcNAc for 6 weeks

6 weeks

1 visit (in-person) at 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GlcNAc-GlcN
• Placebo

Trial Overview The study tests whether GlcNAc, a dietary supplement, increases tear production in those with NGLY1-CDDG. Patients will either receive GlcNAc-GlcN or a placebo without knowing which one they're getting to compare the effects fairly.

How Is the Trial Designed?

Group I: GlcNAc Experimental Treatment 1 Intervention

GlcNAc powder

Group II: Placebo Placebo Group 1 Intervention

Placebo xylose

Who Is Running the Clinical Trial?

Eva Morava-Kozicz

Lead Sponsor

Trials

4

Recruited

80+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Seattle Children's Hospital

Collaborator

Trials

319

Recruited

5,232,000+

Published Research Related to This Trial

N-acetylglucosamine-asparagine (GNA) has been identified as a key biomarker for N-glycanase 1 (NGLY1) deficiency, showing significant differences in levels between affected patients and healthy controls, which can help in identifying patients with this rare disorder.

The study developed a reliable assay to measure GNA levels across various biological samples, demonstrating that elevated GNA levels correlate with the absence of functional NGLY1 and can serve as a potential pharmacodynamic marker and surrogate endpoint in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GlcNAc-Asn is a biomarker for NGLY1 deficiency. Mueller, WF., Zhu, L., Tan, B., et al.[2022]

The first Polish patient diagnosed with NGLY1 deficiency (NGLY1-CDDG) exhibited significant symptoms including global developmental delay, hyperkinetic movement disorder, and hypolacrimia, highlighting the disorder's clinical features.

Whole exome sequencing identified two heterozygous nonsense variants in the NGLY1 gene, reinforcing the importance of genetic testing in diagnosing NGLY1-CDDG, especially in patients with developmental disabilities and movement disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NGLY1 deficiency: Novel patient, review of the literature and diagnostic algorithm. Lipiński, P., Bogdańska, A., Różdżyńska-Świątkowska, A., et al.[2022]

A natural history study involving 29 participants with NGLY1 deficiency revealed severe developmental delays and motor function decline, with most participants scoring below 20 on developmental assessments, indicating significant challenges in growth and development.

The study identified elevated levels of the biomarker GlcNAc-Asn in all participants, which could serve as a potential endpoint for future clinical trials aimed at developing interventions for this rare disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NGLY1 deficiency: a prospective natural history study. Tong, S., Ventola, P., Frater, CH., et al.[2023]

The study identified two novel compound heterozygous mutations in the NGLY1 gene in a 10-month-old infant with NGLY1-related congenital disorder of deglycosylation (NGLY1-CDDG), which is linked to developmental delays, epilepsy, and liver dysfunction.

Whole-exome sequencing (WES) and Sanger sequencing were used to confirm these mutations, providing a genetic basis for the disorder in this rare case, which had not been previously documented.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two novel compound heterozygous mutations in NGLY1as a cause of congenital disorder of deglycosylation: a case presentation. Ge, H., Wu, Q., Lu, H., et al.[2020]

A patient with NGLY1 deficiency exhibited a milder form of the disorder, lacking many typical symptoms such as severe intellectual disability, which suggests a broader range of possible presentations for this condition.

This case expands the understanding of NGLY1 deficiency, indicating that not all patients will present with the severe symptoms commonly associated with the disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanding the NGLY1 deficiency phenotype: Case report of an atypical patient. Nolan, DK., Pastore, MT., McBride, KL.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8863169/

GlcNAc-Asn is a biomarker for NGLY1 deficiency - PMC We demonstrate that N-acetylglucosamine-asparagine (GlcNAc-Asn; GNA), is the analyte most closely associated with NGLY1 deficiency.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05402345

A Study of GlcNAc on Tear Production in NGLY1-CDDG This study is being done to see if the dietary supplement, GlcNAc, improves tear production in patients with NGLY1-CDDG.

3. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT06199531

GS-100 Gene Therapy in Patients With NGLY1 Deficiency Efficacy outcomes will be assessed at baseline and 52 weeks. The co-primary outcomes will be change from baseline in cerebrospinal fluid (CSF) ...

4. academic.oup.com academic.oup.com/hmg/article/32/18/2787/7209579

NGLY1 deficiency: a prospective natural history study This study demonstrates that the profound neurodevelopmental impairments, quality of life, and other outcomes of NGLY1 deficiency do not improve ...

5. withpower.com withpower.com/trial/phase-2-and-3-ngly1-deficiency-11-2022-7f0c0

GlcNAc for NGLY1 Deficiency · Info for Participants Trial Overview The study tests whether GlcNAc, a dietary supplement, increases tear production in those with NGLY1-CDDG. Patients will either receive GlcNAc- ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06199531

Safety and Efficacy of GS-100 Gene Therapy in Patients ... This study is a non-randomized, open-label, dose escalation study of GS-100 gene therapy for NGLY1 deficiency, using a single ICV injection, to assess safety ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2329050125001196

Preclinical pharmacology and safety studies to support an ... The safety and efficacy of GS-100 in patients with NGLY1 deficiency are currently being assessed in an ongoing phase 1/2/3 (NCT06199531 ) clinical trial.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40687377/

Preclinical pharmacology and safety studies to support an ... GS-100 is an AAV9 gene replacement therapy for the treatment of N-glycanase 1 (NGLY1) deficiency, an ultra-rare, recessive disorder ...

9. cell.com cell.com/molecular-therapy-family/methods/pdf/S2329-0501(25)00119-6.pdf

Preclinical pharmacology and safety studies to support an ... NGLY1 deficiency is approximately 1 in 4 million live births. There are currently 42 patients diagnosed with NGLY1 deficiency in the US and ...