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

Mucopolysaccharidosis II Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04007536
• Other study ID #: DNLI-E-0001
• Status: Completed
• Start date: October 23, 2019
• Est. completion date: March 1, 2024

Study information

• Verified date: June 2024
• Source: Denali Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: March 1, 2024
• Est. primary completion date: March 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 30 Years

Eligibility

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 Inclusion Criteria (Part 5):

• 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

Key Inclusion Criteria (Part 6):

• 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

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

Related Conditions & MeSH terms

• Mucopolysaccharidoses
• Mucopolysaccharidosis II

Intervention

Other:
• No Intervention
No Intervention

Locations

Country	Name	City	State
Netherlands	Erasmus Medical Center	Rotterdam	South Holland
United Kingdom	Birmingham Children's Hospital	Birmingham
United Kingdom	Manchester Centre for Genomic Medicine	Manchester
United States	UNC Children's Research Institute	Chapel Hill	North Carolina
United States	UCSF Benioff Children's Hospital	Oakland	California
United States	UPMC | Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Denali Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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