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

NCT04007536 | Completed

• 1 other identifier: DNLI-E-0001
• Study Type: observational
• Target: 18
• Locations: 3 countries
• Sites: 6

Brief Summary

This is a six-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 ≤30 years at the time of enrollment.

Conditions

Mucopolysaccharidosis II

Keywords

MPS-II; Hunter Syndrome; Lysosomal Storage Disease; nMPS II; nnMPS II

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (6)

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

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 outcome assessments are optional in Part 2 for participants aged 18 years or younger; no clinical assessments are planned for participants older than 18 years.

Other: 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

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

Part 5

Participants ≤3 years of age with an undetermined MPS II phenotype. Clinical, neurocognitive, laboratory, and biomarker assessments will be conducted.

Other: No Intervention

Part 6

Participants from 1 to 17 years of age with nMPS II. Clinical, neurocognitive, laboratory, and biomarker assessments will be conducted. Part 6 will also include a single collection of CSF.

Other: No Intervention

Interventions

No Intervention OTHER

No Intervention

Part 1; Part 2; Part 3; Part 4; Part 5; Part 6

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• 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

You may qualify if:

• 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
• 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
• nMPS II participants aged \<8 years
• nnMPS II participants aged 6 to 17 years
• Participants aged ≤ 3 years
• Have undetermined MPS II phenotype
• Do not have a large deletion(s) or rearrangement(s) in the IDS gene or other definitive mutation indicative of nMPS II
• Do not have a DQ \< 85 at the screening/baseline neurocognitive assessment and/or a documented decline of at least 7.5 points in DQ in the previous 6 to 18 months
• Do not have the same IDS gene variant as a blood relative with confirmed nMPS II or nnMPS II
• nMPS II participants aged 1 to 17 years
• Have received an MPS II gene therapy or allogeneic HSCT \> 12 months prior to screening
• Have a post-HSCT or post-gene therapy DQ \< 85 at the screening/baseline neurocognitive assessment and/or a documented decline of at least 7.5 points in DQ in the previous 6 to 18 months

You may not qualify if:

• 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

Sponsors & Collaborators

• Denali Therapeutics Inc.: lead

Study Sites (6)

UCSF Benioff Children's Hospital

Oakland, California, 94609, United States

Location

UNC Children's Research Institute

Chapel Hill, North Carolina, 27514, United States

Location

UPMC | Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Erasmus Medical Center

Rotterdam, South Holland, 3015 GD, Netherlands

Location

Birmingham Children's Hospital

Birmingham, B4 6NH, United Kingdom

Location

Manchester Centre for Genomic Medicine

Manchester, M13 9WL, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, serum, cerebrospinal fluid

MeSH Terms

Conditions

Mucopolysaccharidosis II; Sudden Infant Death; Lysosomal Storage Diseases

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infant Death

Study Officials

• Katia Meirelles, MD

  Denali Therapeutics

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: June 22, 2019
• First Posted: July 5, 2019
• Study Start: October 23, 2019
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2024
• Last Updated: June 10, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); NL (1); GB (2)