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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04007536
Recruitment Status : Recruiting
First Posted : July 5, 2019
Last Update Posted : April 20, 2022
Sponsor:
Information provided by (Responsible Party):
Denali Therapeutics Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment
Mucopolysaccharidosis II 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.).

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Study Type : Observational
Estimated Enrollment : 37 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Prospective, Longitudinal Study of Potential Treatment-Responsive Biomarkers and Clinical Outcomes in Hunter Syndrome
Actual Study Start Date : October 23, 2019
Estimated Primary Completion Date : February 2024
Estimated Study Completion Date : February 2024


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




Primary Outcome Measures :
  1. 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) [ Time Frame: Up to 96 weeks ]
  2. 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 [ Time Frame: Up to 96 weeks ]
  3. 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 [ Time Frame: up to 96 weeks ]

Biospecimen Retention:   Samples With DNA
Whole blood, serum, cerebrospinal fluid


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
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
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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04007536


Locations
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United States, California
UCSF Benioff Children's Hospital Recruiting
Oakland, California, United States, 94609
Contact: Danielle Roth    510-428-3885 ext 4785    Danielle.Roth@ucsf.edu   
Contact       paul.harmatz@ucsf.edu   
Principal Investigator: Paul Harmatz, MD         
United States, North Carolina
UNC Children's Research Institue Recruiting
Chapel Hill, North Carolina, United States, 27514
Contact: Chen Zhu    919-966-1447    czhu@email.unc.edu   
Contact       muenzer@med.unc.edu   
Principal Investigator: Joseph Muenzer, MD         
United States, Pennsylvania
UPMC | Children's Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Dawn Kolar    412-692-8343    kolardr@upmc.edu   
Contact       rajands@upmc.edu   
Principal Investigator: Deepa Soundara Rajan, MD         
Italy
Center for Rare Diseases, Udine University Hospital Recruiting
Udine, Italy, 33100
Contact: Serena Vanlent    +393386265576    serena.valent@asufc.sanita.fvg.it   
Principal Investigator: Maurizio Scarpa, MD         
Netherlands
Erasmus Medical Center Recruiting
Rotterdam, South Holland, Netherlands, 3015 GD
Contact: Jacqueline Hardon    Email:    j.hardon@erasmusmc.nl   
Contact: Dorine Heemskerk    Email:    t.heemskerk@erasmusmc.nl   
Principal Investigator: Hannerieke van den Hout, MD         
United Kingdom
Birmingham Children's Hospital Recruiting
Birmingham, United Kingdom, B4 6NH
Contact: Shashi Watson    +4401213339954    shashi.rana@nhs.net   
Principal Investigator: Julian Raiman, MD         
Manchester Centre for Genomic Medicine Recruiting
Manchester, United Kingdom, M13 9WL
Contact: Simon Jones    0161 7012137    Simon.Jones@mft.nhs.uk   
Sponsors and Collaborators
Denali Therapeutics Inc.
Investigators
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Study Director: Anna Bakardjiev, MD Denali Therapeutics
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Responsible Party: Denali Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT04007536    
Other Study ID Numbers: DNLI-E-0001
First Posted: July 5, 2019    Key Record Dates
Last Update Posted: April 20, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Denali Therapeutics Inc.:
MPS-II
Hunter Syndrome
Lysosomal Storage Disease
nMPS II
nnMPS II
Additional relevant MeSH terms:
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Mucopolysaccharidosis II
Mucopolysaccharidoses
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System