Study designs.
MPS, MPS IIIB
Interventional study NCT02754076, i.e., Study 250-201, was a phase I/II open-label, dose-escalation (Part 1), and stable-dose (Part 2) study involving males and females between 1 and less than 11 years of age (i.e., 12 months and 132 months) with a confirmed diagnosis of MPS IIIB. Three patients, i.e., patients 9001, 9002, and 9003, were enrolled in Study 250-201 Part 1 and received weekly escalating doses, i.e., 30, 100, and 300 mg of tralesinidase alfa via an i.c.v. device such as the Ommaya reservoir and a catheter implanted into the lateral ventricle. Twenty-three patients, 19 of whom were rolled over from our natural history study (The sample size was determined by the number of patients who were rolled over from Study 250-901 into Study 250-201. On the basis of the natural history data for untreated patients with MPS IIIA, 10 points of yearly decline in cognitive DQ score was assumed for the natural course of MPS IIIB, and the SD of the difference in yearly decline between pre- and post-treatment periods within a patient was assumed to be 10. Under these assumptions, a sample size of 20 patients was estimated to provide greater than 90% power to detect an 8-point difference in yearly decline between pre- and post-treatment periods, using a paired The primary objectives were to (a) evaluate the safety and tolerability of tralesinidase alfa administered to patients with MPS IIIB via an implanted i.c.v. reservoir and catheter, and (b) evaluate the impact of tralesinidase alfa on cognitive function as assessed by the DQ. Additional objectives were to (a) evaluate the impact of tralesinidase alfa on cognitive function as assessed by AEq score; (b) characterize the PK of tralesinidase alfa in CSF and plasma; (c) characterize the immunogenicity of tralesinidase alfa in CSF and serum; (d) evaluate the impact of tralesinidase alfa treatment on CSF, serum, and urine GAGs; and (e) evaluate the impact of tralesinidase alfa treatment on brain structure, liver size, and spleen size as assessed by MRI.