AVTX-801 D-galactose Supplementation in SLC35A2-CDG

Evaluation of Efficacy and Safety of D-galactose Supplementation in SLC35A2-CDG, a Disorder of Hypogalactosylation

This is a multicenter, randomized, double-blind, placebo-controlled, cross-over study to evaluate the efficacy and safety of AVTX-801 in subjects with SLC35A2-CDG

Study Overview

• Status: Not yet recruiting
• Conditions: SLC35A2-CDG - Solute Carrier Family 35 Member A2 Congenital Disorder of Glycosylation
• Intervention / Treatment: Drug: Placebo; Drug: AVTX-801

Detailed Description

This is a multicenter, open-label, withdrawal and treatment study assessing the efficacy, safety, and tolerability of CERC-801 in subjects with SLC35A2-CDG. Upon completion of the Screening Visit all subjects will be asked to stop their ongoing treatment of medical food D-galactose and will enter a 6-week run-in period with CERC-801 at a dose of 1 g/kg/day. Following the run-in period, subjects will begin a (up to) 6-week washout period in which each subject will stop taking CERC-801. During this washout period, subjects will be closely monitored for clinical signs and symptoms related to or suspected to be related to withdrawal of D-galactose therapy (e.g., fasting blood glucose <50 mg/dl, hypoglycemic episode, bleeding, persistent or recurrent muscle cramps, and signs suggesting rhabdomyolysis). In addition, laboratory tests (ATIII, Factor XI, and comprehensive metabolic panel [CMP]) will be completed weekly during this washout. Subjects will be instructed to measure fasting blood glucose level by glucometer daily and whenever they have symptoms of hypoglycemia during the washout period.

Upon manifestation of symptoms, clinically relevant changes to laboratory parameters, or completion of the 6-week washout period, the key clinical laboratory parameters (ATIII, ALT, AST, and fasting blood glucose) will be assessed to establish a post-washout baseline. At this baseline, subjects will resume treatment with CERC-801 at the dose of 1 g/kg/day for 24 weeks (6 months). At the end of 24 weeks, the key clinical laboratory parameter assessment will be repeated as a part of the efficacy analysis.

Upon completion of the efficacy evaluation period (at the end of 24 weeks), subjects will enter a long-term safety follow-up period of 12 months with CERC-801 at a dose of 1.5 g/kg/day.

This study is designed in collaboration with the Frontiers in Congenital Disorders of Glycosylation Consortium / National Institutes of Health (NIH) study to limit patient burden as much as possible.

Approximately 10 subjects are planned to be included and dosed with CERC-801 in this study.

Subjects must have biologically and genetically proven SLC35A2-CDG, and at least one historical measurement of NPCRS and relevant laboratory tests values (complete blood count [CBC], ATIII, activated partial thromboplastin time [APTT, CMP, thyroid stimulating hormone [TSH], free thyroxin [T4], insulin-like growth factor binding protein 3 [IGBP3], insulin-like growth factor 1 [IgF1], and glycan analysis by mass spectrometry) before initiation of unregulated D galactose therapy.

Subject will not be eligible if they have aldolase-B deficiency, galactosemia, hemolytic uremic syndrome, or severe anemia; or if they have experienced severe AEs (severe diarrhea, vomiting, constipation, galactosuria, or increased liver glycogen storage) from oral galactose. Additionally, in the investigator's opinion, subjects with a history of galactose intolerance can be excluded.

Efficacy will be evaluated by measuring changes in laboratory parameters (ATIII activity, quantitative N-glycan assay, glycosylated transferrin APTT, ALT, AST, and fasting blood glucose) from baseline, NPCRS, and GAS.

Safety will be monitored throughout the study. Safety will be measured by monitoring of AEs, clinical laboratory tests, urinalysis, vital signs, and liver scans during the study; and change in the levels of metabolic biomarkers (erythrocyte galactose-1-phosphate and urine galactitol) and patient-reported outcomes using GAS from baseline.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mary Freeman, MS, CGC; Phone Number: 212-659-1434; Email: mary.freeman@mssm.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 40 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Molecular confirmation of SLC35A2 genetic variant
• Age > 1 month
• Presence of seizures, chronic vomiting, chronic constipation, or chronic diarrhea
• A parent or legal guardian must be available and willing to provide consent on behalf of minor subjects or adult subjects who are unable to give informed consent due to developmental disabilities.
• Use of contraception in females > age 8 years
• Previously performed eye exam within last year

Exclusion Criteria

• Aldolase-B deficiency
• Galactosemia
• Hemolytic uremic syndrome
• Hemoglobin < 7 mg/dL
• LFTs > 3x ULN
• Previously experienced severe AEs from oral galactose (severe diarrhea, vomiting, constipation, galactosuria, or increased liver glycogen storage)
• Other history of galactose intolerance as determined by the investigator
• Currently treated with ketogenic diet
• Current enrollment in another trial involving investigational compounds
• Ongoing dietary D-galactose supplementation
• Use of investigational compounds
• Pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AVTX-801, then Placebo; Each treatment period is 24 weeks, with 6-week washout period in between.	Drug: Placebo; Matching placebo; Drug: AVTX-801; Medical grade D-galactose dosage:2.0 g/kg/day; Other Names: D-Galactose
Placebo Comparator: Placebo, then AVTX-801; Each treatment period is 24 weeks, with 6-week washout period in between.	Drug: Placebo; Matching placebo; Drug: AVTX-801; Medical grade D-galactose dosage:2.0 g/kg/day; Other Names: D-Galactose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of major motor seizure frequency	Seizure burden assessed by change from baseline in 28-day major motor seizure frequency	28 days
Number of vomiting episodes	Vomiting frequency in 28-day from baseline	28 days
Bristol Stool Form Scale (BSFS)	Constipation/diarrhea assessed by scale improvement toward normal stool forms from baseline in average daily 28-day Bristol Stool form scale. The BSFS classifies stool into 7 groups, type 1 (hardest) to type 7 (softest). Type 3 and Type 4 would be more indicative of normal stool.	average daily 28 days

Collaborators and Investigators

• Sponsor: Eva Morava-Kozicz
• Collaborators: Children's Hospital of Philadelphia; National Institute of Neurological Disorders and Stroke (NINDS); Rare Diseases Clinical Research Network
• 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 (Estimated): January 1, 2027
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

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 (Actual): June 29, 2025
• Last Update Submitted That Met QC Criteria: June 27, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Carbohydrate Metabolism, Inborn Errors; Congenital Disorders of Glycosylation
• Other Study ID Numbers: 19-005271; U54NS115198 (U.S. NIH Grant/Contract)

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