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A Study of Mucopolysaccharidosis Type IIIB (MPS IIIB)

Completed
Conditions
Mucopolysaccharidosis Type 3 B
MPS 3 B
Mucopolysaccharidosis Type IIIB
MPS III B
Registration Number
NCT02493998
Lead Sponsor
Allievex Corporation
Brief Summary

Mucopolysaccharidosis type IIIB (MPS IIIB, also known as Sanfilippo Syndrome Type B) is a severe neurodegenerative disorder. The purpose of this study is to learn more about the health problems in patients with MPS IIIB and how to measure these problems over time. It will particularly look at how the disease develops in young children. This is an observational study, so no experimental drug will be given. The results from this study will help us design future studies to measure whether these health problems get better when we give experimental drug for MPS IIIB.

Detailed Description

This is a multicenter, multinational, longitudinal, observational study in subjects 1 through 10 years of age who have been diagnosed with MPS IIIB. Data will be prospectively collected from 20 to 30 subjects to understand the clinical progression of MPS IIIB in terms of neurocognitive function, behavior, quality of life, imaging characteristics, genotype, and biochemical markers of disease burden. This information may help inform the design and interpretation of subsequent interventional studies.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
22
Inclusion Criteria
  • Individuals eligible to participate in 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 ≤ 10 years of age and has an age-equivalent of ≥ 12 months on the VABS-II
  • DQ ≥ 50 (determined by BSID-III or KABC-II)
  • Has presented with signs/symptoms consistent with MPS IIIB; for individuals who have not presented with signs/symptoms of disease (e.g., 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
Exclusion Criteria
  • Has another neurological illness that may have caused cognitive decline (e.g., trauma, meningitis, or hemorrhage) before study entry
  • Requires ventilation support, except for noninvasive support at night
  • 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)
  • 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 wellbeing or safety, or the interpretability of the subject's clinical data.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Neurocognitive functionScreening, baseline, and every 12 weeks, for up to 48-96 weeks

A neurodevelopmental assessment will be performed using standardized developmental tests to provide quantifiable measures of neurocognitive function.

Imaging characteristicsBaseline and every 24 weeks, for up to 48-96 weeks

MRI will be used to assess changes in size of various organs affected by the disease, including brain, liver and spleen.

Behavioral functionBaseline and every 12 weeks, for up to 48-96 weeks

Disease-related behaviors will be assessed using an MPS III-specific behavior rating scale.

HearingBaseline and every 24 weeks, for up to 48-96 weeks

The function of conductive and sensorineural hearing pathways will be assessed using tympanometry and auditory brainstem response (ABR).

Sleep habitsBaseline and every 24 weeks, for up to 48-96 weeks

Patient sleep habits will be assessed using specific questionnaires.

Quality-of-lifeBaseline and every 24 weeks, for up to 48-96 weeks

Multiple QOL tools will be used to capture physical, mental, and social well-being of the patient as well as to examine the impact of the patient's disease on the parent/guardian and family.

Biochemical, Molecular, Cellular and Genetic Markers of Disease BurdenBaseline and every 24 weeks, for up to 48-96 weeks

Blood, urine, and CSF samples will be used to evaluate biochemical, molecular cellular, and genetic/genomic aspects of MPS IIIB.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (8)

Melbourne Children's Trials Centre

🇦🇺

Melbourne, Victoria, Australia

Children's Hospital and Research Center Oakland

🇺🇸

Oakland, California, United States

Hospital Clinico Universitario de Santiago

🇪🇸

Santiago de Compostela, Spain

Gazi University Faculty of Medicine

🇹🇷

Ankara, Turkey

Somers Clinical Research Facility, Great Ormond Street Hospital

🇬🇧

London, United Kingdom

MacKay Memorial Children's Hospital

🇨🇳

Taipei, Taiwan

University Medical Center Hamburg Eppendorf, Department of Pediatrics

🇩🇪

Hamburg, Germany

Fundacion Cardioinfantil-Instituto de Cardiologia

🇨🇴

Bogota, Colombia

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