A Study of GlcNAc on Tear Production in NGLY1-CDDG

A Phase II Randomized, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating Effect Of GlcNAc On Tear Production In Individuals With NGLY1-CDDG

In patients with NGLY1-CDDG, the disorder can lead to eye damage due to not being able to produce enough tears. This study is being done to see if the dietary supplement, GlcNAc, improves tear production in patients with NGLY1-CDDG.

Study Overview

• Status: Active, not recruiting
• Conditions: NGLY1 Deficiency
• Intervention / Treatment: Drug: GlcNAc-GlcN; Other: Placebo

Detailed Description

This study is a multicenter randomized, double-blind, placebo-controlled trial of GlcNAc supplementation for improvement of tear production in NGLY1-CDDG. Clinical history and screening data will be reviewed to determine subject eligibility. If a subject is already on GlcNAc, a washout period of 1 month will be required prior to consent and randomization. Interested subjects who have a molecularly confirmed diagnosis of NGLY1-CDDG will be consented. Baseline data will be collected prior to randomization at treatment initiation. Subjects will then be randomized to placebo or GlcNAc. They will be administered weight-dependent doses of GlcNAc or an equivalent volume of placebo enterally for 6 weeks, followed by open label weight-dependent doses of GlcNAc for 6 weeks. A visit for evaluation and collection of lab samples will be conducted at 6 and 12 weeks.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Previously molecularly confirmed NGLY1-CDDG
• Between the ages of 1 year old to 60 years old
• 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. Willingness of subject or legal guardian to provide consent.
• Non-pregnant, non-lactating female subjects of childbearing potential who are heterosexually active must agree to use a highly effective method of contraception for the duration of the study. A highly effective method of birth control is defined as one that results in a low failure rate (i.e., <1% per year) when used consistently and correctly, such as oral/injectable/inserted/implanted/transdermal contraceptives, condom with diaphragm, condom with spermicide, diaphragm with spermicide, intrauterine hormone- releasing system, or intrauterine device (IUD), or sexual abstinence. Contraception is not required where at least 6 weeks have passed since sterilization, defined as females having undergone one of the following surgeries: hysterectomy, bilateral tubal ligation or occlusion, bilateral oophorectomy, or bilateral salpingectomy; and males who are vasectomized. Contraception is not required where females are postmenopausal (defined as 12 consecutive months of spontaneous amenorrhea and age ≥51 years)..

Exclusion Criteria

• Hypersensitivity to any of the components of the placebo
• History of treatment with GlcNAc within 28 days of Visit 1
• 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
• Shellfish allergy
• Planned eye surgery within 3 months of enrollment
• • Females that are pregnant, nursing or less than 6 months postpartum or attempting to conceive

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GlcNAc; GlcNAc powder	Drug: GlcNAc-GlcN; GlcNAc powder - weight-dependent dose
Placebo Comparator: Placebo; Placebo xylose	Other: Placebo; Placebo xylose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in tear production from baseline in placebo vs GlcNAc group	The primary endpoint of the study is the difference in tear production from baseline in individuals with NGLY1-CDDG between the placebo and the GlcNAc group after 6 weeks of blinded therapy, as measured by Schirmer II test which is a tool that helps assess the amount of tears in the eyes.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of eye infections needing treatments	Patient/family reported number of eye infections needing treatment in last month after 6 weeks of blinded therapy and at 12 weeks after 6 weeks of open-label administration of GlcNAc.	6 weeks, 12 weeks
Frequency of eye redness needing treatments	Patient/family reported frequency of eye redness after 6 weeks of blinded therapy and at 12 weeks after 6 weeks of open-label administration of GlcNAc.	6 weeks, 12 weeks
Frequency of eye tearing/watering	Patient/family reported frequency of eye tearing/watering after 6 weeks of blinded therapy and at 12 weeks after 6 weeks of open-label administration of GlcNAc.	6 weeks, 12 weeks
Frequency of light sensitivity	Patient/family reported frequency of light sensitivity after 6 weeks of blinded therapy and at 12 weeks after 6 weeks of open-label administration of GlcNAc.	6 weeks, 12 weeks
Frequency of wind sensitivity	Patient/family reported frequency of wind sensitivity after 6 weeks of blinded therapy and at 12 weeks after 6 weeks of open-label administration of GlcNAc.	6 weeks, 12 weeks
Difference in tear production from baseline	Difference in tear production, as measured by Schirmer II test, at 12 weeks after 6 weeks of open-label administration of GlcNAc.	12 weeks

Collaborators and Investigators

• Sponsor: Eva Morava-Kozicz
• Collaborators: Children's Hospital of Philadelphia; Seattle Children's Hospital
• Investigators: Principal Investigator: Eva Morava-Kozicz, MD, PhD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 28, 2022
• First Submitted That Met QC Criteria: May 28, 2022
• First Posted (Actual): June 2, 2022

Study Record Updates

• Last Update Posted (Estimated): July 8, 2025
• Last Update Submitted That Met QC Criteria: July 3, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Congenital Disorders of Glycosylation
• Other Study ID Numbers: CHOP 23-020868; 8404 (Other Identifier: FCDGC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No