AVTX-801 D-galactose Supplementation in SLC35A2-CDG

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.