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
Sponsors
Allievex Corporation
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 (1) a cognitive AEq score = 18 months, (2) a DQ score = 20 and (3) no evidence of improvement during the 250-201 study in secondary or exploratory efficacy endpoints. • Would not benefit from enrolling in the study in the opinion of the investigator • Has received stem cell, gene therapy or ERT (other than AX 250) for MPS IIIB • Has contraindications for neurosurgery (e.g., congenital heart disease, severe respiratory impairment, or clotting abnormalities) • Has contraindications for MRI scans (e.g., 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 AX 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 AX 250 administered to subjects with MPS IIIB by an implanted ICV reservoir and catheter • Evaluate the impact of long-term AX 250 treatment on cognitive function in patients with MPS IIIB as assessed by age equivalent score (AE);Secondary Objective: • Evaluate the impact of long-term AX 250 treatment on cognitive function in patients with MPS IIIB as assessed by development quotient (DQ) • Characterize immunogenicity of long-term AX 250 treatment in CSF and serum • Evaluate the impact of long-term AX 250 treatment on CSF, serum and urine GAGs • Evaluate the impact of long-term AX 250 treatment on brain structure assessed by magnetic resonance imaging (MRI) • Evaluate the impact of long-term AX 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 AX 250 administered to subjects with MPS IIIB by an implanted intracerebroventricular (ICV) reservoir and catheter. To evaluate the impact of long-term AX 250 treatment on cognitive function in patients with MPS IIIB as assessed by age equivalent score (AEq).;Timepoint(s) of evaluation of this end point: Safety evaluation will include continuous monitoring of AEs and concomitant medications. Clinical laboratory assessments at Baseline and every 4W the first 96W, Q12W thereafter. CSF for cell count, protein, and glucose collected prior to each weekly infusion. A complete physical examination performed at Baseline and every 24W thereafter. The exam includes assessment of general appearance, vital signs, measurements of height, weight and head circumference, a detailed neurological examination, and assessment of cardiovascular, respiratory, and gastrointestinal systems. Brief physical exams weekly dosing visits when complete exams are not performed. ECG and EEG performed at the EoT. Brain imaging (MRI or CT) to monitor for asymptoma | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary objectives of this study are: To evaluate the long-term impact of AX 250 treatment on cognitive function in patients with MPS IIIB as assessed by development quotient (DQ) To characterize single- and repeated-dose pharmacokinetics (PK) of AX 250 in cerebrospinal fluid (CSF) and plasma To characterize immunogenicity of long-term AX 250 treatment in CSF and serum To evaluate the impact of AX 250 treatment on CSF, serum and urine GAGs To evaluate the impact of AX 250 treatment on brain structure assessed by magnetic resonance imaging (MRI) To evaluate the impact of AX 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
Colombia, Germany, Spain, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
Allievex Corporation
Outcome results
None listed