Clinical trial NCT02493998: A Study of Mucopolysaccharidosis Type IIIB (MPS IIIB)
Official title: A Prospective, Observational Study of Mucopolysaccharidosis Type IIIB (MPS IIIB)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Mucopolysaccharidosis Type IIIB
Mucopolysaccharidosis Type 3 B
MPS III B
MPS 3 B
Keywords: Sanfilippo Syndrome Type B
Lead sponsor: Allievex Corporation
Sponsor class: INDUSTRY
First posted: 2015-07-10
Enrollment: 22
Sex: ALL
Minimum age (years): 1
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study Population: Subjects diagnosed with MPS IIIB

Males and females 1 through 10 years of age (ie, until they turn 11) with a documented diagnosis of MPS IIIB are eligible to participate in this observational study. Up to approximately 5 subjects 6 to 10 years old, inclusive, will be enrolled; the remaining subjects will be 1 to 5 years old, inclusive. Additional entry criteria follow.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Neurocognitive function
timeFrame: Screening, baseline, and every 12 weeks, for up to 48-96 weeks
measure: Imaging characteristics
timeFrame: Baseline and every 24 weeks, for up to 48-96 weeks
measure: Behavioral function
timeFrame: Baseline and every 12 weeks, for up to 48-96 weeks
measure: Hearing
timeFrame: Baseline and every 24 weeks, for up to 48-96 weeks
measure: Sleep habits
timeFrame: Baseline and every 24 weeks, for up to 48-96 weeks
measure: Quality-of-life
timeFrame: Baseline and every 24 weeks, for up to 48-96 weeks
measure: Biochemical, Molecular, Cellular and Genetic Markers of Disease Burden
timeFrame: Baseline and every 24 weeks, for up to 48-96 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Children's Hospital and Research Center Oakland
state: California
city: Melbourne
country: Australia
facility: Melbourne Children's Trials Centre
state: Victoria
city: Bogota
country: Colombia
facility: Fundacion Cardioinfantil-Instituto de Cardiologia
city: Hamburg
country: Germany
facility: University Medical Center Hamburg Eppendorf, Department of Pediatrics
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago
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: Somers Clinical Research Facility, Great Ormond Street Hospital
Study officials:
affiliation: Allievex Corporation
name: Allievex Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Okur I, Ezgu F, Giugliani R, Muschol N, Koehn A, Amartino H, Harmatz P, de Castro Lopez MJ, Couce ML, Lin SP, Batzios S, Cleary M, Solano M, Peters H, Lee J, Nestrasil I, Shaywitz AJ, Maricich SM, Kuca B, Kovalchin J, Zanelli E. Longitudinal Natural History of Pediatric Subjects Affected with Mucopolysaccharidosis IIIB. J Pediatr. 2022 Oct;249:50-58.e2. doi: 10.1016/j.jpeds.2022.06.005. Epub 2022 Jun 13.