Safety, Tolerability and Efficacy of ICV AX 250 Treatment in MPS IIIB -OLE

Study Overview
=================
Brief Summary
-----------------
This is a Phase 3B/4, multicenter, multinational, open label study to further evaluate intracerebroventricular (ICV) delivered AX 250 treatment in MPS IIIB subjects that complete Study 250-202 for up to an additional 3 years (144 weeks) of treatment with AX 250 administered by ICV infusion every other week. Subjects will be evaluated for neurocognitive function, communication, adaptive behavior, quality of life, imaging characteristics and biochemical markers of disease burden. Safety will be assessed by adverse events, clinical labs, and physical exams.

Official Title
-----------------
Open-Label Multicenter Extension Study to Further Evaluate Safety, Tolerability and Efficacy of Intracerebroventricular AX 250 Treatment in Mucopolysaccharidosis Type IIIB (MPS IIIB, Sanfilippo Syndrome Type B) Patients

Conditions
-----------------
MPS III B

Intervention / Treatment
-----------------
* Drug: AX 250


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Must have completed 240 weeks of Study 250-202 and enter 250-401 within 8 weeks of dosing completion. Provides 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 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 Exclusion Criteria: Has (1) a cognitive age equivalent (AEq ) score ≤ 18 months, (2) a development quotient (DQ) score ≤ 20, and (3) no evidence of improvement during the 250-202 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 enzyme replacement therapy (other than AX 250) for MPS IIIB Has a history of poorly controlled seizure disorder Is prone to complications from ICV 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
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single arm<br>AX 250 300 mg - open label | Drug: AX 250<br>* biweekly infusion by intracerebroventricular (ICV) infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary - neurocognition | the rate of change in score from neurocognitive assessment using validated scale | baseline to 144 weeks of treatment |