Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome Type B, MPS IIIB) MedDRA version: 20.0 Level: LLT Classification code 10056918 Term: Sanfilippo's syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.1 Level: PT Classification code 10056890 Term: Mucopolysaccharidosis III System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Allievex Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part 1: Dose Escalation Period: Has deficient NAGLU enzyme activity at Screening. Blood for NAGLU enzyme activity will be collected and analyzed centrally. Is = 1 and 1 and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Part 1: Dose Escalation Phase: Has received stem cell, gene therapy, or enzyme replacement therapy 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 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 Part 2: Stable Dose Period: Has received stem cell, gene therapy or ERT 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) Is prone to complications from intraventricular drug administration, including patients with hydrocephalus or ventricular shunts Has received any investigational medication 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: To evaluate the 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 AX 250 on cognitive function in patients with MPS IIIB as assessed by development quotient (DQ).;Secondary Objective: To evaluate the impact of AX 250 on cognitive function in patients with MPS IIIB as assessed by age equivalent score (AEq). To characterize single- and repeated-dose pharmacokinetics (PK) of AX 250 in cerebrospinal fluid (CSF) and plasma. To characterize immunogenicity of AX 250 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 MRI. To evaluate the impact of AX 250 treatment on adaptive function derived from the Vineland Adaptive Behavior Scales, 2nd edition (VABS-II).;Primary end point(s): To evaluate the 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 AX 250 on cognitive function in patients with MPS IIIB as assessed by developmental quotient (DQ).;Timepoint(s) of evaluation of this end point: Safety + tolerability reviews: monitoring of AEs +concomitant medic.; clinical lab assess. at Screening, prior to/day after 1st dose at each dose level and Q4W until next dose escalation in Pt.1 + Screening, prior to/day after 1st dose + Q4W thereafter in Pt.2;CSF for cell count, protein, glucose collected prior to weekly infusions; pre/post-dose blood samples for serial PK analysis monitored for glucose level; complete physical exam at Screening, Baseline and dose escalation visits in Pt.1 and Baseline and Wks 24 and 48 . in Pt.2,phys. exams at weekly dosing visits when complete exams not performed; ECG+ EEG at Screening +EoS of study. Brain imaging to monitor asymptomatic subdural hygroma formation up to Q4W. Neurocogni | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary objectives of this study are: *to evaluate the impact of AX 250 on cognitive function in patients with MPS IIIB as assessed by age equivalent score (AEq) *to characterize single- and repeated-dose pharmacokinetics (PK) of AX 250 in cerebrospinal fluid (CSF) and plasma *to characterize immunogenicity of AX 250 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 (VABS-II).;Timepoint(s) of evaluation of this end point: VABS-II/Neurocognitive tests (from which AEq is derived) at Baseline in Part1, and Baseline, Weeks 12, 24, 36, 48 in Part2. Sampling of CSF and blood (plasma) for serial PK and GAG analyses will be following the first dose and subsequent dose escalations in Part1 and for doses at Baseline, and Weeks 5, 12 and 36 in Part2. CSF and blood (plasma) samples will also be used for trough PK performed Q4W in Part2. CSF and serum will be drawn throughout the study to analyze immunogenicity. Urine will be collected for GAGs/creatinine analysis prior to initial dosing at each dose level and Q4W until the next dose escalation in Part1, and Baseline and Q4W thereafter in Part2. Brain structure will be evaluated by MRI during Part1 and Part2 Baseline visits and at Weeks 24 and 48 in Part2. | — |
Countries
Australia, Colombia, Germany, Spain, Taiwan, Turkey, United Kingdom
Contacts
Public ContactClinical Trials Information
Allievex Corporation
Outcome results
None listed