Natural History Study to Characterise the Course of Disease Progression in Participants With Mucopolysaccharidosis Type IIIB

Alexion Pharmaceuticals

Status: Terminated

Conditions: MPS IIIB (Sanfilippo B Syndrome)

Study type: Observational

Funder types: Industry

Identifiers

NCT02293408

NGLU-NH02

Details and patient eligibility

About

The objectives of this study are to describe the clinical and biochemical characteristics and course of disease progression in participants with Mucopolysaccharidosis type IIIB (MPS IIIB)

Enrollment: 30 patients

Sex: All

Ages: 1+ year old

Volunteers: No Healthy Volunteers

Inclusion criteria

A participant must meet all of the following inclusion criteria to be eligible for this study:

1. The participant has a definitive diagnosis of MPS IIIB, as determined by either of the following:

   1. Documented deficiency in alpha-N-acetyl-glucosaminidase (NAGLU) enzyme activity or
   2. Documented functionally-relevant mutations in both alleles of the NAGLU gene.

2. The participant is at least 1 year of age (biological age).

3. The participant or the participant's parent provides informed consent.

4. The participant is willing and able to comply with protocol requirements to the extent that may be expected of a participant with cognitive impairment.

In addition to the eligibility criteria above, a participant must meet all of the following criteria for Component 2:

1. The participant meets criterion a or criterion b below.

   a. The participant is considered to be at risk of rapid disease progression based on at least 1 of the following criteria:

   i. The participant has documented mutations of the NAGLU gene that are reported to be linked to rapid disease progression (for example, disease onset before 6 years of age), or

   ii. The participant has a sibling, or other first- or second-degree relative with rapidly progressing MPS IIIB (for example, disease onset before 6 years of age).

   b. The participant had disease onset prior to 6 years of age (biological age), as defined by:

   i. Cognitive delay evaluated by Bayley Scales of Infant Development, Third Edition (BSID-III) or Kaufman Assessment Battery for Children, Second Edition (KABC-II), or

   ii. Language delay, plateauing, or regression of language skills as determined by the Investigator (for example, participant uses isolated words, associated words such as 2-word combinations, sentences, poor or reduced language, and/or difficult to understand).

2. The participant has an age equivalent of ≥1 year on the Vineland Adaptive Behavior Scales, Second Edition (Vineland II).

Exclusion criteria

A participant who meets any of the following exclusion criteria will be ineligible for this study:

1. The participant has visual or hearing impairments sufficient to preclude cooperation with neurodevelopmental testing.
2. The participant has a history of poorly-controlled seizure disorder.
3. The participant is currently receiving medication, which, in the Investigator's opinion, would be likely to substantially confound interpretation of the results (for example, the participant has been on the current dose of psychotropic medication for less than 3 months).
4. The participant is receiving a newly increased dose of melatonin (for example, less than 3 months on current dose).
5. The participant has previously received an investigational therapy for MPS IIIB (with the exception of high dose Genistein >150 milligram/kilogram (mg/kg)/day, which will require a minimum of 3 months wash-out before entering the study) or has had hematopoietic stem cell transplant (HSCT).
6. The participant has any other prior or ongoing medical condition that may present a safety risk, interfere with study compliance, or confound data interpretation.

Trial design

30 participants in 2 patient groups

Component 1

Description:

Component 1 involved an evaluation of the clinical characteristics of MPS IIIB in participants based on a retrospective chart review to collect information on demographics, clinical history, diagnostic tests, treatments, clinical chemistry and hematology test results, physical examination findings, anthropometric data, radiology results, and supportive interventions performed over a period of up to 6 weeks.

Component 2

Description:

Component 2 involved a longitudinal evaluation of the course of disease progression in a subset of participants considered to be at risk of rapid disease progression, who, after completing Component 1, were to be prospectively followed for a period of at least 1 year (Longitudinal Follow-Up) and up to 3 years total (Extended Follow-Up).