Clinical trial NCT04007536: A Study of Potential Treatment-Responsive Biomarkers and Clinical Outcomes in Hunter Syndrome
Official title: A Prospective, Longitudinal Study of Potential Treatment-Responsive Biomarkers and Clinical Outcomes in Hunter Syndrome
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Mucopolysaccharidosis II
Keywords: MPS-II
Hunter Syndrome
Lysosomal Storage Disease
nMPS II
nnMPS II
Lead sponsor: Denali Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2019-07-05
Enrollment: 18
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.

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.).

Eligibility 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

Primary outcomes:
measure: 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)
timeFrame: Up to 96 weeks
measure: 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
timeFrame: Up to 96 weeks
measure: 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
timeFrame: up to 96 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: Chapel Hill
country: United States
facility: UNC Children's Research Institute
state: North Carolina
city: Pittsburgh
country: United States
facility: UPMC | Children's Hospital of Pittsburgh
state: Pennsylvania
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: South Holland
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Manchester
country: United Kingdom
facility: Manchester Centre for Genomic Medicine
Study officials:
affiliation: Denali Therapeutics
name: Katia Meirelles, MD
role: STUDY_DIRECTOR
References: