A Study of Potential Treatment-Responsive Biomarkers and Clinical Outcomes in Hunter Syndrome

A Prospective, Longitudinal Study of Potential Treatment-Responsive Biomarkers and Clinical Outcomes in Hunter Syndrome

This is a four-part prospective, multicenter, multiregional observational study of patients with mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, to assess biomarkers potentially related to disease severity and/or treatment response and prospectively assess the progression of disease in participants with MPS II who are aged 2 through 10 years (Part 1), 2 through 30 years (Part 2), < 8 years (Part 3), and 6 to < 17 years (Part 4) at the time of enrollment.

Study Overview

• Status: Completed
• Conditions: Mucopolysaccharidosis II
• Intervention / Treatment: Other: No Intervention

Detailed Description

This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).

• Study Type: Observational
• Enrollment (Actual): 18

Contacts and Locations

Study Locations

• Italy
  • Udine, Italy, 33100
    • Center for Rare Diseases, Udine University Hospital
• Netherlands
  • South Holland
    • Rotterdam, South Holland, Netherlands, 3015 GD
      • Erasmus Medical Center
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Children's Hospital
  • Manchester, United Kingdom, M13 9WL
    • Manchester Centre for Genomic Medicine
• United States
  • California
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • UNC Children's Research Institue
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC | Children's Hospital of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 30 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients ≤ 30 years with a confirmed diagnosis of MPS II based on IDS (iduronate 2-sulfatase) enzyme activity and documented mutation in the IDS gene

Description

Key Inclusion Criteria (Part 1):

• Participants aged 2 through 10 years
• nMPS II subgroup: participants with a development quotient (DQ) <85 and/or a decline of at least 7.5 points in DQ, assessed at least 6 months apart, or with the same genetic mutation as a blood relative with confirmed nMPS II

Key Inclusion Criteria (Part 2):

• Participants aged 2 through 30 years
• nMPS II subgroup: patients with an age-adjusted DQ <85 and/or a decline of 10 points or more in DQ in the previous 6 months or more, or with the same genetic mutation as a blood relative with confirmed nMPS II
• Scheduled to undergo general anesthesia or CSF sampling for non-study-related medical reasons and parent(s)/legally authorized representative consent to donate CSF for research purposes during that procedure, or an adult patient is able to provide consent and agrees to participation in the study for CSF collection/donation

Key Inclusion Criteria (Part 3):

• nMPS II participants aged <8 years

Key Inclusion Criteria (Part 4):

• nnMPS II participants aged 6 to 17 years

Key Exclusion Criteria (All Parts):

• Have unstable medical condition that would make participation in the study unsafe or would interfere with necessary medical care
• Have received any central nervous system (CNS)-targeted MPS II investigational therapy within the previous 6 months

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Part 1; Participants from 2 through 10 years of age who have MPS II. Clinical, neurocognitive, laboratory, and biomarker assessments will be conducted.	Other: No Intervention; No Intervention
Part 2; Participants from 2 through 30 years of age who have MPS II; Part 2 will entail a single collection of cerebrospinal fluid (CSF), urine, and blood. Clinical assessments are optional in Part 2.	Other: No Intervention; No Intervention
Part 3; Participants <8 years of age who have the neuronopathic form of mucopolysaccharidosis type II (nMPS II). Clinical, neurocognitive, laboratory, and biomarker assessments will be conducted.	Other: No Intervention; No Intervention
Part 4; Participants 6 to 17 years of age with the non-neuronopathic form of mucopolysaccharidosis type II (nnMPS II). Clinical, neurocognitive, laboratory, and biomarker assessments will be conducted.	Other: No Intervention; No Intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes in adaptive behavior over time as measured by Vineland Adaptive Behavior Scales, Second Edition (VABS II) and/or Vineland Adaptive Behavior Scales, Third Edition (Vineland-3)	Up to 96 weeks
Changes in neurocognition over time as measured by Bayley Scales of Infant and Toddler Development, 3rd Edition; Kaufman Assessment Battery for Children, 2nd Edition; or Wechsler Intelligence Scale for Children, Fifth Edition	Up to 96 weeks
Changes in levels of total urine glycosaminoglycans (GAGs), levels of heparan sulfate (HS) and dermatan sulfate (DS) in cerebrospinal fluid (CSF), urine and/or blood	up to 96 weeks

Collaborators and Investigators

• Sponsor: Denali Therapeutics Inc.
• Investigators: Study Director: Anna Bakardjiev, MD, Denali Therapeutics

Publications and helpful links

Helpful Links

• Engage Hunter Website

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2019
• Primary Completion (Actual): March 1, 2024
• Study Completion (Actual): March 1, 2024

Study Registration Dates

• First Submitted: June 22, 2019
• First Submitted That Met QC Criteria: July 1, 2019
• First Posted (Actual): July 5, 2019

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Hunter Syndrome; Lysosomal Storage Disease; nMPS II; nnMPS II; MPS-II
• 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: DNLI-E-0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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