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

Denali Therapeutics

Status: Completed

Conditions: Mucopolysaccharidosis II

Treatments: Other: No Intervention

Study type: Observational

Funder types: Industry

Identifiers

NCT04007536

DNLI-E-0001

Details and patient eligibility

About

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.

Full 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.).

Enrollment: 18 patients

Sex: All

Ages: Under 30 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

18 participants in 6 patient groups

Part 1

Description:

Participants from 2 through 10 years of age who have MPS II. Clinical, neurocognitive, laboratory, and biomarker assessments will be conducted.

Treatment:

Other: No Intervention

Part 2

Description:

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.

Treatment:

Other: No Intervention

Part 3

Description:

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.

Treatment:

Other: No Intervention

Part 4

Description:

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.

Treatment:

Other: No Intervention

Part 5

Description:

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

Treatment:

Other: No Intervention

Part 6

Description:

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.

Treatment:

Other: No Intervention