Study of IV VTS-270 for Infantile Liver Disease Associated With Niemann-Pick Disease, Type C

Study Summary

Niemann-Pick disease, type C (NPC) is a lethal, autosomal recessive, lysosomal storage disorder characterized by neurodegeneration in early childhood and death in adolescence. NPC results from mutation of either the Niemann-Pick C1 disease (NPC1) (\~95% of cases) or NPC2 genes. NPC is characterized by the endolysosomal storage of unesterified cholesterol and lipids in both the central nervous system and peripheral tissues such as the liver. Individuals with NPC demonstrate progressive central nervous system decline including inability to coordinate balance, gait, extremity and eye movements. Acute liver disease in the newborn/infant period is frequently observed, but subsequently resolves. However, chronic, sub-clinical liver disease persists. Intrathecal 2-Hydroxypropyl-β-Cyclodextrin (HP-β-CD, VTS-270), also known as adrabetadex, has proven effective in reducing the signs and prolonging life in animal models and Phase 1/2a data support efficacy in NPC1 patients. Adrabetadex (VTS-270) also has been shown to be effective in treating liver disease in the NPC1 cat. This Phase 1/2a, open-label, multiple ascending dose trial will evaluate whether adrabetadex (VTS-270) administered intravenously is effective in treating acute liver disease in NPC1 infants.

Primary Outcome

This bile acid, 5α-cholanic acid-3β, 5α, 6β-triol N-(carboxymethyl)-amide, is elevated \>99% of NPC1 subjects, is largely generated in the liver and therefore provides a biochemical measure of oxidizable lysosomal unesterified cholesterol in liver tissue. The primary outcome measure in phase 1 of the study is the change in plasma levels of 5α-cholanic acid-3β, 5α, 6β-triol N-(carboxymethyl)-amide measured in nanograms/ml from baseline to 6 weeks. The primary outcome measure in phase 2 of the stu

Interventions

• DRUG VTS-270