A Treatment Study of Mucopolysaccharidosis Type IIIB

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02754076
• Date of registration: 27/02/2016
• Prospective Registration: Yes
• Primary sponsor: Allievex Corporation
• Public title: A Treatment Study of Mucopolysaccharidosis Type IIIB MPS IIIB
• Scientific title: A Phase 1/2 Open-Label Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Intracerebroventricular AX 250 in Patients With Mucopolysaccharidosis Type IIIB (MPS IIIB, Sanfilippo Syndrome Type B)
• Date of first enrolment: April 2016
• Target sample size: 23
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02754076
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Colombia, Germany, Spain, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: Allievex Medical Monitor
• Affiliation: Allievex Corporation

Key inclusion & exclusion criteria

Inclusion Criteria:

Individuals eligible to participate in Part 1 of this study must meet all of the following
criteria:

- Has deficient NAGLU enzyme activity at Screening. Blood for NAGLU enzyme activity will
be collected and analyzed centrally.

- Is = 1 and < 11 years of age (at least 1 of the 3 subjects in Part 1 must be = 1 and <
6 years of age)

- Has presented with signs/symptoms consistent with MPS IIIB; for individuals who have
not presented with signs/symptoms of disease (eg, siblings of known patients), the
determination of eligibility will be at the discretion of the BioMarin medical monitor
in conjunction with the site investigator.

- 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

Individuals eligible to participate in Part 2 of this study must meet all of the following
criteria:

- Participated in and met protocol requirements for transitioning from Study 250-901 or
participated in Part 1 of Study 250-201

- Written informed consent from parent or legal guardian and assent from subject, if
required

Exclusion Criteria:

Individuals who meet any of the following exclusion criteria are ineligible to participate
in Part 1 of the study:

- Has received stem cell, gene therapy or ERT 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 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

Individuals who meet any of the following exclusion criteria are ineligible to participate
in Part 2 of this study:

- Has received stem cell, gene therapy or ERT 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)

- 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



Age minimum: 1 Year
Age maximum: 10 Years
Gender: All

Health Condition(s) or Problem(s) studied

MPS III B

Mucopolysaccharidosis Type IIIB

Intervention(s)

Drug: AX 250

Primary Outcome(s)

Safety Evaluation of weekly infusions of AX 250 (Part 1 & Part 2) - Number of participants with abnormal clinical laboratory values and/or Adverse Events that are related to treatment. [Time Frame: Entire study period, up to 124 weeks]

Development Quotient (DQ) as efficacy variable with analysis of rate of change of DQ score on treatment vs. rate of change of DQ score prior to treatment. [Time Frame: Assessed at study end, up to 124 weeks. Collected at: Part 1 - Baseline; Part 2 - Weeks 12, 24, 36, & 48]

Secondary Outcome(s)

Evaluate GAG levels in urine [Time Frame: Assessed at study end, up to 124 weeks. Collected at: Each weekly visit as relevant through completion of Part 1 and Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, as relevant in Part 2]

Evaluate GAG levels in plasma [Time Frame: Assessed at study end, up to 124 weeks. Collected at: Each weekly visit as relevant through completion of Part 1 and Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, as relevant in Part 2]

Characterize area under concentration curve (AUC) of AX 250 in cerebrospinal fluid (CSF) and plasma as relevant through completion of Part 1 and Part 2 [Time Frame: Study end, up to 124 weeks. Collected at: Pre-dose, 0, 4, 10, 24, 48, 72, 96, 168 hours post-dose for the first dose during each dose escalation in Part 1. Pre-dose, 0, 4, 10, 24, 48, 72, 96, 168 hours post-dose for Baseline, Weeks 5, 12, 36 in Part 2.]

Evaluate the impact of AX 250 treatment on brain structure assessed by magnetic resonance imaging (MRI) [Time Frame: Assessed at study end, up to 124 weeks. Part 1 - Screening and Baseline; Part 2 - Screening, Baseline, Week 24, and Week 48]

Characterize immunogenicity of AX 250 total anti-drug anti-body (TAb) in cerebrospinal fluid (CSF) and serum as relevant through completion of Part 1 and Part 2 [Time Frame: Assessed at study end, up to 124 weeks. Collected at: First dose during each dose escalation in Part 1, and Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 in Part 2]

Characterize maximum concentration (Cmax) of AX 250 in cerebrospinal fluid (CSF) and plasma as relevant through completion of Part 1 and Part 2 [Time Frame: Study end, up to 124 weeks. Collected at: Pre-dose, 0, 4, 10, 24, 48, 72, 96, 168 hours post-dose for the first dose during each dose escalation in Part 1. Pre-dose, 0, 4, 10, 24, 48, 72, 96, 168 hours post-dose for Baseline, Weeks 5, 12, 36 in Part 2.]

Evaluate GAG levels in cerebrospinal fluid (CSF) [Time Frame: Assessed at study end, up to 124 weeks. Collected at: Each weekly visit as relevant through completion of Part 1 and Part 2]

Secondary ID(s)

250-201

Source(s) of Monetary Support

Please refer to primary and secondary sponsors