AVTX-801 D-galactose Supplementation in SLC35A2-CDG
Study Details
Study Description
Brief Summary
This is a multicenter, open-label, withdrawal and treatment study assessing the efficacy, safety, and tolerability of CERC-801 in subjects with SLC35A2-CDG.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Main study arm - AVTX-801 subjects will wash out from food grade D-galactose then be put on medical grade D-galactose |
Drug: AVTX-801
Medical grade D-galactose
Other Names:
|
| Placebo Comparator: Placebo placebo crossover |
Drug: Placebo
Placebo
|
Outcome Measures
Primary Outcome Measures
- Change in the composite score of the Nijmegen Pediatric CDG Rating Scale [12 months]
Changes in the composite Nijmegen Pediatric CDG Rating Scale (NPCRS) score from post washout baseline to 12 months
- Change in Alanine aminotransferase level [12 months]
• Change in the key clinical laboratory parameters alanine aminotransferase [ALT], aspartate aminotransferase [AST]) from post-washout baseline to 12 months
- Change in Aspartate aminotransferase level [12 months]
• Change in the key clinical laboratory parameters alanine aminotransferase [ALT], aspartate aminotransferase [AST]) from post-washout baseline to 12 months
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Subject/legally authorized representative (LAR) is able to understand and provide written informed consent, and assent (as applicable) to participate in this study.
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Subject has biologically and genetically proven SLC35A2-CDG.
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Subject has at least one historical measurement of NPCRS before initiation of unregulated D galactose therapy.
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Subject has relevant laboratory test values (CBC, ATIII, APTT, CMP, TSH, free T4, IGBP3, IgF1, and glycan analysis by mass spectrometry) before initiation of unregulated D galactose therapy.
Exclusion Criteria:
-
Subject has aldolase B deficiency, galactosemia, hemolytic uremic syndrome, or severe anemia.
-
In the investigator's opinion, subject is not able or willing to comply with the trial requirements.
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In the investigator's opinion, subject has a history of galactose intolerance that precludes the subject from participation in this study.
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In the investigator's opinion, subject has previously experienced any of the following severe adverse events from oral galactose:
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Severe diarrhea
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Severe, recurrent vomiting
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Constipation
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Galactosuria
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Increased liver glycogen storage
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Use of investigational compounds or ongoing unregulated D-galactose supplementation or current enrollment in another trial involving investigational compounds
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Eva Morava-Kozicz
Investigators
- Principal Investigator: Eva Morava-Kozicz, MD, PhD, Mayo Clinic
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 19-005271