US-based Ultragenyx Pharmaceutical has started dosing first patient in the pivotal Phase III trial of recombinant human beta-glucuronidase (rhGUS, UX003), an investigational therapy to treat Mucopolysaccharidosis 7 (MPS 7), also known as Sly syndrome.
The global, randomised, placebo-controlled, blind-start Phase III trial will evaluate the efficacy and safety of rhGUS in 12 patients between five and 35 years old and they will be randomised to one of four groups.
One group will begin rhGUS therapy immediately, while the other three will start first with placebo and cross over to rhGUS at different predefined time points in a blinded manner.
The company said that the new trial design generates treatment data from all 12 patients, improving the statistical power of the trial relative to a traditional parallel-group design.
Based on data from the Phase I/II trial, patients will be dosed with 4mg/kg of rhGUS every other week for up to a total of 48 weeks, and all groups will receive a minimum of 24 weeks of treatment with rhGUS.
The trial's primary objective is to determine the efficacy of rhGUS as determined by the reduction in urinary GAG excretion after 24 weeks of treatment.
The company has already reached an agreement with both the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) on the pivotal trial design.
The agreement with FDA was reached after deciding that their evaluation of the pivotal Phase III trial will be based on the totality of the data on a patient-by-patient basis.
EMA has agreed that approval under exceptional circumstances could be possible based on a single positive Phase III trial using urinary GAG excretion as the primary endpoint with a trend toward improvement in the most important clinical endpoints.
The company intends to report data from the Phase III trial in the first half of 2016.