A Treatment Study of Mucopolysaccharidosis Type IIIB
- Registration Number
- NCT02754076
- Lead Sponsor
- Allievex Corporation
- Brief Summary
The study's primary objectives are to evaluate the safety and tolerability of AX 250 administered to subjects with MPS IIIB via an ICV reservoir and catheter and to evaluate the impact of AX 250 on cognitive function in patients with MPS IIIB as assessed by the Development Quotient.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 23
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description AX 250 AX 250 In Part 1, patients will receive up to 3 escalating doses of AX 250 (30, 100 and 300 mg) via ICV infusion every week until the maximum tolerated tested dose (MTTD) is established. In Part 2, patients will receive weekly doses of AX 250 via ICV infusion that will continue for 48 weeks at the MTTD established in Part 1.
- Primary Outcome Measures
Name Time Method 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. Assessed at study end, up to 124 weeks. Collected at: Part 1 - Baseline; Part 2 - Weeks 12, 24, 36, & 48 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. Entire study period, up to 124 weeks Number of participants with abnormal clinical laboratory values and/or Adverse Events that are related to treatment.
- Secondary Outcome Measures
Name Time Method Evaluate GAG levels in cerebrospinal fluid (CSF) Assessed at study end, up to 124 weeks. Collected at: Each weekly visit as relevant through completion of Part 1 and 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 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 plasma 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 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) 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 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 Evaluate GAG levels in urine 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
Trial Locations
- Locations (7)
Gazi Üniversitesi Tıp Fakültesi
🇹🇷Ankara, Turkey
Mackay Memorial Hospital
🇨🇳Taipei, Taiwan
Hospital Clinico Universitario de Santiago
🇪🇸Santiago de Compostela, Spain
University Medical Center Hamburg Eppendorf, Department of Pediatrics
🇩🇪Hamburg, Germany
Somers Clinical Research Facility, Great Ormond Street Hospital
🇬🇧London, United Kingdom
Fundación Cardio Infantil - Instituto de Cardiología
🇨🇴Bogotá, Colombia
Children's Hospital Oakland
🇺🇸Oakland, California, United States