Clinical trial NCT03784287: A Treatment Extension Study of Mucopolysaccharidosis Type IIIB
Official title: A Multicenter, Multinational, Extension Study to Evaluate the Long Term Safety and Efficacy of Intracerebroventricular AX 250 in Patients With Mucopolysaccharidosis Type IIIB (MPS IIIB, Sanfilippo Syndrome Type B)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Mucopolysaccharidosis Type IIIB
MPS III B
Keywords: Sanfilippo Syndrome Type B
Lead sponsor: Allievex Corporation
Sponsor class: INDUSTRY
First posted: 2018-12-21
Enrollment: 20
Sex: ALL
Minimum age (years): 0
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objectives of this study are to evaluate the long-term safety and tolerability of AX 250 administered to subjects with MPS IIIB by an implanted ICV reservoir and catheter and to evaluate the impact of long-term AX 250 treatment on cognitive function in patients with MPS IIIB as assessed by developmental quotient (DQ).


Eligibility 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.

Exclusion Criteria:

* Has both (1) a cognitive AEq score ≤ 18 months, and (2) a DQ score ≤ 20
* 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 (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 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

Primary outcomes:
measure: Evaluate the Long-term safety and tolerability of AX 250 administered in up to 33 subjects with MPS IIIB by assessing the number of participants with abnormal clinical laboratory values and/or Adverse Events related to the treatment
timeFrame: Entire study period, up to 240 weeks
measure: Evaluating the impact of long-term AX 250 treatment on cognitive function in up to 33 patients with MPS IIIB as assessed by developmental quotient (DQ)
timeFrame: Entire study period, up to 240 weeks
Secondary outcomes:
measure: Evaluate the impact of long-term AX 250 treatment on cognitive function in up to 33 patients with MPS IIIB as assessed by age equivalent score (AEq)
timeFrame: Entire study period, up to 240 weeks
measure: Characterize immunogenicity as measured by IgE levels, formation of anti-AX 250, IGF1 and IGF2 antibodies in Cerebrospinal fluid (CSF) and serum.
timeFrame: Entire study period, up to 240 weeks
measure: Evaluate the impact of long-term AX 250 treatment on Heparan sulfate (HS) levels in cerebrospinal fluid (CSF), serum and urine.
timeFrame: Entire study period, up to 240 weeks
measure: Evaluate the impact of long-term AX 250 treatment on brain structure assessed by magnetic resonance imaging (MRI)
timeFrame: Entire study period, up to 240 weeks
measure: Evaluate the impact of long-term AX 250 treatment on adaptive function derived from the Vineland Adaptive Behavior Scales, 2nd edition (VABS-II)
timeFrame: Entire study period, up to 240 weeks
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Children's Hospital and Research Center Oakland
state: California
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital Pittburgh
state: Pennsylvania
city: Bogotá,
country: Colombia
facility: Fundación Cardio Infantil - Instituto de Cardiología
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
city: Santiago de Compostela
country: Spain
facility: Complexo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario
city: Taipei
country: Taiwan
facility: MacKay Memorial Children's Hospital
city: Ankara
country: Turkey
facility: Gazi University Faculty of Medicine
city: London
country: United Kingdom
facility: Great Ormond Street Hospital For Children, NHS Foundation Trust
Study officials:
affiliation: Allievex Corporation
name: Medical Monitor, MD
role: STUDY_DIRECTOR
References: