Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome Type B, MPS IIIB) MedDRA version: 20.1 Level: PT Classification code 10056890 Term: Mucopolysaccharidosis III System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.0 Level: LLT Classification code 10056918 Term: Sanfilippo's syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: N/A
Product Code: BMN 250
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not available
Current Sponsor code: BMN 250
Other descriptive name: RHNAGLU-IGF2
Concentration u
Sponsors
BioMarin Pharmaceutical Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Must have completed 48 weeks in Part 2 of Study 250-201 and enter 250-202 within 8 weeks of study completion • Written informed consent from parent or legal guardian and assent from subject, if required • Has the ability to comply with protocol requirements, in the opinion of the investigator • Males and females who are of reproductive age should practice true abstinence, defined as no sexual activity, during the study and for 6 months after the study has been completed (or withdrawal from the study). If sexually active and not practicing true abstinence, males and females of reproductive age must use a highly effective method of contraception while participating in the study. • If female with childbearing potential, must have a negative pregnancy test at the Screening visit and be willing to have additional pregnancy tests during the study. Are the trial subjects under 18? yes Number of subjects for this age range: 33 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Individuals who meet any of the following exclusion criteria are ineligible to participate in this study: • Has both a DQ score < 20 and DQ score < 25% that of the 250-201 Baseline DQ score at the 250-201 Week 48 visit • Would not benefit from enrolling in the study in the opinion of the investigator • Has received stem cell, gene therapy or ERT (other than BMN 250) for MPS IIIB • Has contraindications for neurosurgery (eg, congenital heart disease, severe respiratory impairment, or clotting abnormalities) • Has contraindications for MRI scans (eg, cardiac pacemaker, metal fragment or chip in the eye, or aneurysm clip in the brain) • Has a history of poorly controlled seizure disorder • Is prone to complications from intraventricular drug administration, including patients with hydrocephalus or ventricular shunts • Has received any investigational medication other than BMN 250 within 30 days prior to the Baseline visit or is scheduled to receive any investigational drug during the course of the study • Has a medical condition or extenuating circumstance that, in the opinion of the investigator, might compromise the subject’s ability to comply with protocol requirements, the subject’s well-being or safety, or the interpretability of the subject’s clinical data. • Is pregnant at any time during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •Evaluate the long-term safety and tolerability of BMN 250 administered to subjects with MPS IIIB by an implanted ICV reservoir and catheter • Evaluate the impact of long-term BMN 250 treatment on cognitive function in patients with MPS IIIB as assessed by development quotient (DQ);Secondary Objective: • Evaluate the impact of long-term BMN 250 treatment on cognitive function in patients with MPS IIIB as assessed by age equivalent score (AEq) • Characterize immunogenicity of long-term BMN 250 treatment in CSF and serum • Evaluate the impact of long-term BMN 250 treatment on CSF, serum and urine GAGs • Evaluate the impact of long-term BMN 250 treatment on brain structure assessed by magnetic resonance imaging (MRI) • Evaluate the impact of long-term BMN 250 treatment on adaptive function derived from the Vineland Adaptive Behavior Scales, 2nd edition (VABS-II);Primary end point(s): To evaluate the lon-term safety and tolerability of BMN 250 administered to subjects with MPS IIIB by an implanted intracerebroventricular (ICV) reservoir and catheter. To evaluate the lon-term impact of BMN 250 treatment on cognitive function in patients with MPS IIIB as assessed by developmental quotient (DQ).;Timepoint(s) of evaluation of this end point: The safety evaluation will include continuous monitoring of AEs and concomitant medications. Clinical laboratory assessments will be performed at Baseline and every 4 weeks for the first 96 weeks, then Q12W thereafter. CSF for cell count, protein, and glucose will be collected prior to each weekly infusion. A complete physical examination will be performed at Baseline and every 24 weeks thereafter. The exam includes an assessment of general appearance, vital signs, measurements of height, weight and head circumference, a detailed neurological examination, and an assessment of cardiovascular, respiratory, and gastrointestinal systems. Brief physical exams are performed at wee | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary objectives of this study are: *to evaluate the long-term impact of BMN 250 treatment on cognitive function in patients with MPS IIIB as assessed by age equivalent score (AEq) *to characterize single- and repeated-dose pharmacokinetics (PK) of BMN 250 in cerebrospinal fluid (CSF) and plasma *to characterize immunogenicity of long-term BMN 250 treatment in CSF and serum *to evaluate the impact of BMN 250 treatment on CSF, serum and urine GAGs *to evaluate the impact of BMN 250 treatment on brain structure assessed by magnetic resonance imaging (MRI) *To evaluate the impact of BMN 250 treatment on adaptive function derived from the Vineland Adaptive Behavior Scales, 2nd edition (VABSII).;Timepoint(s) of evaluation of this end point: The CSF, as well as blood collected at less frequent intervals, will be used for GAG analyses and/or exploratory analyses of the biochemical, molecular, cellular and genetic/genomic aspects of MPS IIIB. CSF and blood (serum) will be drawn throughout the study to analyze immunogenicity Urine will be collected for GAG and creatinine analyses as well as for exploratory analyses at Baseline and every 24 weeks thereafter. Brain structure will be evaluated by MRI during Baseline visits and at Weeks 24 and 48. | — |
Countries
Argentina, Australia, Colombia, Germany, Spain, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
BioMarin Pharmaceutical Inc.
Outcome results
None listed