The investigators propose to conduct a single arm phase I/II study of Vosoritide (also called VOXZOGO® and BMN111) in 6 pediatric patients with mucopolysaccaridosis (MPS) types IVA and VI; 3 patients with each disease. This will be a single center study performed at UCSF Children's Hospital, Oakland, under the direction of Dr. Paul Harmatz, Professor in Residence in the Department of Pediatric Gastroenterology.~Mucopolysaccharidoses (MPS) are a group of ultra rare genetic lysosomal storage diseases caused by deficiency in various enzymes responsible for the breakdown of glycosaminoglycans (GAGs), leading to progressive accumulations of GAGs in the tissues and organs. Patients with MPS have severe growth deficits and growth-related decreased quality of life. In this study, the MPS disorders which have the most severe growth deficits will be the focus, MPS IVA and VI.~Enzyme replacement therapies (ERT) have been developed and approved for use in MPS. Though ERT has improved functional outcomes it does not lead to complete reversal of disease progression. Patients maintained on ERT continue to experience significant growth deficits.~Vosoritide, a CNP analog and recently approved FDA drug, has been shown to improve linear growth in patients with achondroplasia.~This proposal is for a Phase I/II, single arm, open label study of vosoritide therapy provided subcutaneously at 15 ug/kg/day for 48 weeks to 6 patients with MPS IVA or VI. Subjects will be included if they are > 5 years and < 10 years, Tanner pubertal stage 1 with a height Z-score of <-2.0 or less than 2 cm change in height velocity over the year prior to screening. Prior to enrollment in the interventional arm of study, subjects will be followed for a minimum of 24 weeks to gather information on safety profiles and determine pre-treatment (baseline) annualized growth velocity. The primary study endpoint is the determination of safety and tolerability of daily vosoritide treatment in MPS. Segmental growth, other functional assessments, inflammation, and bone/collagen markers, as well as quality of life will also be assessed.
This is a Phase I/II, single arm, open label study of vosoritide therapy provided subcutaneously at 15 ug/kg/day for 48 weeks to 6 patients with MPS IVA or VI. Prior to enrollment in the interventional arm of study, subjects will be followed for a minimum of 24 weeks to gather information on safety profiles and determine annualized growth velocity. The primary study endpoint is the determination of safety and tolerability of daily vosoritide treatment in MPS. Exploratory endpoints include changes in linear and segmental growth as well as biomarkers of growth and bone metabolism.