Mucopolysaccharidosis Type II Natural History

A Retrospective and Cross-sectional Study to Evaluate Neurodevelopmental Status in Pediatric Subjects With Severe Mucopolysaccharidosis Type II (Hunter Syndrome)

Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is caused by a deficiency of iduronate-2-sulfatase (IDS) leading to an accumulation of glycosaminoglycans (GAGs) in tissues of MPS II patients, resulting in characteristic storage lesions and diverse disease sequelae, and in patients with the more severe form of the disease, irreversible neurocognitive decline and higher morbidity and mortality than in patients with the attenuated form of the disease.

There is currently limited information on the natural history of MPS II, especially with respect to neurocognitive decline in patients with the more severe form of the disease. This study is planned to be an observational medical records review study (data collected retrospectively and no investigational product treatment or procedures) in subjects with the severe form of MPS II. Collectively, the data may inform the design of future MPS II gene therapy treatment studies and may be utilized as historical comparative control data.

Study Overview

• Status: Completed
• Conditions: Mucopolysaccharidosis II

• Study Type: Observational
• Enrollment (Actual): 36

Contacts and Locations

Study Locations

• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre
• United Kingdom
  • Manchester, United Kingdom
    • Manchester Centre for Genomic Medicine
• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh - UPMC: Program for Neurodevelopment in Rare Disorders

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Children diagnosed with Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome

Description

Inclusion Criteria:

1. Documented diagnosis of MPS II confirmed by enzyme activity as measured in plasma, fibroblasts, or leukocytes

2. The subject has at least one of the neurocognitive assessments listed below, which occurred prior to age 6 and in or after 2006 in their medical records.

   1. Bayley Scales of Infant and Toddler Development (BSID), any version
   2. Differential Ability Scale (DAS), any version
   3. Griffiths Mental Development Scale (GMDS), any version
   4. Kaufman Assessment Battery for Children (KABC), any version
   5. Kinder Infant Development Scale (KIDS)
   6. Kyoto Scale of Psychological Development (KSPD), any version
   7. Leiter International Performance Scale (LIPS), any version
   8. Mullen Scales of Early Learning (MSEL), any version
   9. Vineland Adaptive Behavior Scales (VABS), any version
   10. Wechsler Intelligence Scale for Children (WISC), any version
   11. Wechsler Preschool and Primary Scale of Intelligence (WPPSI), any version
3. If the subject has undergone hematopoietic stem cell transplantation (HSCT), they must have at least one neurocognitive assessment prior to HSCT.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Retrospective; An observational medical records review study (data collected retrospectively) in subjects with the severe form of MPS II.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive function over time, as indicated by results of neurocognitive measures documented in medical chart.	There are 10 neurocognitive measures that provide intelligence quotients (IQ) scores and/or developmental quotients (DQ) scores.	Up to 10 years old

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of general organ involvement and specific characteristics of severe MPS II as documented in medical chart.	Documentation in medical chart regarding date and age of onset of: Disease Characteristics, General Appearance, Neurologic/Psychiatric, Cardiovascular, Ocular, Musculoskeletal, Auditory, Respiratory, Gastroenterology/Urinary, Interventional Medications, Other Interventions, ER and Hospitalization History, MRI History, ECG History	Up to 10 years old
Age of onset of general organ involvement and specific characteristics of severe MPS II as documented in medical chart.	Documentation in medical chart regarding date and age of onset of: Disease Characteristics, General Appearance, Neurologic/Psychiatric, Cardiovascular, Ocular, Musculoskeletal, Auditory, Respiratory, Gastroenterology/Urinary, Interventional Medications, Other Interventions, ER and Hospitalization History, MRI History, ECG History	Up to 10 years old

Collaborators and Investigators

• Sponsor: REGENXBIO Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2017
• Primary Completion (Actual): March 22, 2022
• Study Completion (Actual): March 22, 2022

Study Registration Dates

• First Submitted: February 13, 2018
• First Submitted That Met QC Criteria: May 7, 2018
• First Posted (Actual): May 18, 2018

Study Record Updates

• Last Update Posted (Actual): April 26, 2022
• Last Update Submitted That Met QC Criteria: April 22, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Hunter Syndrome; Natural History; glycosaminoglycans; Iduronate-2-sulfatase
• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Mucopolysaccharidosis II; Mucopolysaccharidoses
• Other Study ID Numbers: RGX-121-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No