Natural History Study of Patients With Mucopolysaccharidosis Type IIIB (MPS IIIB, Sanfilippo Syndrome Type B)

NCT01509768 | Completed

• 1 other identifier: HGT-SNB-088
• Study Type: observational
• Target: 19
• Locations: 3 countries
• Sites: 4

Brief Summary

The purpose of this study is to evaluate the natural course of disease progression in Mucopolysaccharidosis Type III (MPS IIIB) patients who are untreated to identify potential surrogate endpoints that may be utilized in future treatment trials of MPS IIIB using predefined assessments including standardized clinical, biochemical, neurocognitive, developmental, and imaging measures.

Conditions

Sanfilippo Syndrome Type B

Keywords

MPS IIIB

Outcome Measures

Primary Outcomes (1)

• evaluate the course of disease progression in patients with MPS IIIB who are untreated with any investigational products to inform possible future treatment studies

  13 months

Study Arms (1)

No treatment

This is a longitudinal, prospective, observational, natural history study of patients with MPS IIIB to identify endpoints that may be used for future ERT trials via standardized clinical, biochemical, neurocognitive, developmental, behavioral and imaging measures

Eligibility Criteria

• Age: 1 Year - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Patients with a documented diagnosis of MPS IIIB and who are currently untreated with investigational products (drugs/device) for this disease. Patient must also be ≥ 1 year and \< 10 years of age with an age equivalent on the Vineland Adaptive Behavior Scales (VABS) of ≥ 1 year.

You may qualify if:

• Each patient must meet all of the following criteria to be enrolled in this study.
• Definitive diagnosis of MPS IIIB, as determined by one of the following:
• Documented deficiency in alpha-N-acetylglucosaminidase (NAGLU) enzyme activity of ≤10% of the lower limit of the normal range as measured in fibroblasts, leukocytes, plasma, or serum (based on normal range for diagnosis of MPS IIIB). Patients who do not already have a documented deficiency of NAGLU activity will provide a blood sample during screening for determination of NAGLU activity level in their serum. OR
• Two documented mutations in the NAGLU gene. Patients who do not already have a documented genotype of NAGLU will provide a blood sample during screening for NAGLU genotyping.
• The patient is ≥1 and \< 10 years of age and has an age equivalent on the Vineland Adaptive Behavior Scales (VABS) of ≥1 year
• The patient is medically stable, in the opinion of the Investigator, to accommodate the protocol requirements, including travel and assessments, without placing an undue burden on the patient/patient's family.

You may not qualify if:

• Patients will be excluded from the study if they meet any of the following criteria at screening:
• Presence of significant non-MPS IIIB related central nervous system (CNS) impairment or behavioral disturbances, sufficient, in the opinion of the Investigator, to preclude performance of study neurocognitive and developmental testing procedures, or that would confound the scientific integrity or interpretation of study assessments.
• Visual or hearing impairment sufficient to preclude cooperation with neurodevelopmental testing.
• Patient has a known or suspected hypersensitivity to anesthesia or is thought to be at an unacceptable risk from anesthesia, due to airway compromise or other conditions, in the opinion of the Investigator.
• Personal history or family history of neuroleptic malignant syndrome, malignant hyperthermia, or other anesthesia-related concerns.
• History of poorly controlled seizure disorder.
• Currently receiving psychotropic or other medications, which in the Investigator's opinion would be likely to substantially confound test results.
• History of bleeding disorder, inability to abstain from medications that affect blood clotting(e.g., aspirin, Non-steroidal anti-inflammatory drug (NSAIDs)), or history of their ingestion within 1 week prior to a lumbar puncture.
• History of complications from previous lumbar punctures that, in the opinion of the Investigator, place the patient at increased risk from this procedure.
• The patient is participating, plans to participate, or participated in a clinical trial of another investigational medicinal product, or has received a vaccination, within the 30 days prior to the study or for less than 5 half lives (whichever is longer) of the investigational product.
• History of hematopoietic stem cell or bone marrow transplant.
• Unable to assent, or the patient's parent(s) or patient's legal guardian(s) is/are unable to understand the nature, scope, and possible consequences of the study, or do/does not agree to comply with the protocol defined schedule of assessments.
• Patient is unable to comply with the protocol (e.g., has a clinically relevant medical condition making implementation of the protocol difficult, unstable social situation, or otherwise unlikely to complete the study) or is, in the opinion of the Investigator, otherwise unsuited for the study.
• The patient has any item (braces, tattoos, etc) which would exclude the patient from being able to undergo MRI according to local Institutional Policy, or the patient has any other situation that would exclude the patient from undergoing any other procedure required in this study.
• The patient is pregnant.

Sponsors & Collaborators

• Shire: lead

Study Sites (4)

Children's Hospital and Research Center

Oakland, California, 94609-1809, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55454, United States

Location

Johannes Gutenberg University Medical Center

Mainz, 55131, Germany

Location

Great Ormond Street Hospital for Children

London, WC1N 3JH, United Kingdom

Location

Related Publications (1)

• Whitley CB, Cleary M, Eugen Mengel K, Harmatz P, Shapiro E, Nestrasil I, Haslett P, Whiteman D, Alexanderian D. Observational Prospective Natural History of Patients with Sanfilippo Syndrome Type B. J Pediatr. 2018 Jun;197:198-206.e2. doi: 10.1016/j.jpeds.2018.01.044. Epub 2018 Apr 13.

  PMID: 29661560 DERIVED

Related Links

• To obtain more information on the study, click here/on this link.

Biospecimen

Retention: SAMPLES WITH DNA

blood (plasma and serum), cerebrospinal fluid (CSF), urine

MeSH Terms

Conditions

Mucopolysaccharidosis III

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2012
• First Posted: January 13, 2012
• Study Start: April 9, 2012
• Primary Completion: October 10, 2013
• Study Completion: October 10, 2013
• Last Updated: March 17, 2021

Record last verified: 2021-03

Locations

DE (1); GB (1); US (2)