Mucopolysaccharidosis IINCT04007536
A Study of Potential Treatment-Responsive Biomarkers and Clinical Outcomes in Hunter Syndrome
An observational study of Mucopolysaccharidosis II, run by Denali Therapeutics Inc. at 6 sites in 3 countries.
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… Read more about this study
- Who is it for?
- Ages Up to 30 years
- Conditions the study is for
- Mucopolysaccharidosis II
- How many people
- 18 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 23 Oct 2019to 1 Mar 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
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
Who may be able to join
- 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
Show all 15Show fewer
- 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
Who cannot join
- 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 locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
United States3 sites
UNC Children's Research Institute
Chapel Hill, North Carolina, 27514
UCSF Benioff Children's Hospital
Oakland, California, 94609
UPMC | Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
United Kingdom2 sites
Birmingham Children's Hospital
Birmingham, B4 6NH
Manchester Centre for Genomic Medicine
Manchester, M13 9WL
Netherlands1 site
Erasmus Medical Center
Rotterdam, South Holland, 3015 GD
About this study
Official title: A Prospective, Longitudinal Study of Potential Treatment-Responsive Biomarkers and Clinical Outcomes in Hunter Syndrome
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.
Read the 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.).
- Conditions
- Mucopolysaccharidosis II
- Being tested
- No Intervention
- Keywords
- MPS-II, Hunter Syndrome, Lysosomal Storage Disease, nMPS II, nnMPS II
- Medical subject headings
- Mucopolysaccharidosis II, Sudden Infant Death, Lysosomal Storage Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No InterventionOther
No Intervention
| Study group | Role | What they receive |
|---|---|---|
| Part 1 | Participants from 2 through 10 years of age who have MPS II. Clinical, neurocognitive, laboratory, and biomarker assessments will be conducted. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Other: No Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Measured: 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
Measured: up to 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2019
- Study start23 Oct 2019
- Primary completion1 Mar 2024
- Study completion1 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mucopolysaccharidosis IIStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Denali Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Katia Meirelles, MD, Study director, Denali Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04007536
- Sponsor's protocol ID
- DNLI-E-0001
- Status last verified
- Jun 2024
- First submitted
- 22 Jun 2019
- Last updated
- 10 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Longitudinal Study of Potential Treatment-Responsive Biomarkers and Clinical Outcomes in Hunter Syndrome
- ClinicalTrials.gov ID
- NCT04007536
- Acronym / sponsor ID
- DNLI-E-0001
- Conditions
- Mucopolysaccharidosis II
- Keywords
- MPS-II, Hunter Syndrome, Lysosomal Storage Disease, nMPS II, nnMPS II
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Denali Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- 23 Oct 2019 (actual)
- Primary completion
- 1 Mar 2024 (actual)
- Study completion
- 1 Mar 2024 (actual)
- First posted
- 5 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Part 1 | – | Other: No InterventionParticipants from 2 through 10 years of age who have MPS II. Clinical, neurocognitive, laboratory, and biomarker assessments will be conducted. |
| Part 2 | – | Other: No InterventionParticipants 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. |
| Part 3 | – | Other: No InterventionParticipants <8 years of age who have the neuronopathic form of mucopolysaccharidosis type II (nMPS II). Clinical, neurocognitive, laboratory, and biomarker assessments will be conducted. |
| Part 4 | – | Other: No InterventionParticipants 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. |
| Part 5 | – | Other: No InterventionParticipants ≤3 years of age with an undetermined MPS II phenotype. Clinical, neurocognitive, laboratory, and biomarker assessments will be conducted. |
| Part 6 | – | Other: No InterventionParticipants 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. |
Who may qualify
- Ages
- Up to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- 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
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No InterventionNo Intervention | Other | Part 1, Part 2, Part 3, Part 4, Part 5, Part 6 |
Primary outcome
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katia Meirelles, MD study director
Denali Therapeutics
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Mucopolysaccharidosis II, run by Denali Therapeutics Inc. at 6 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, United Kingdom, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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) (time frame: Up to 96 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2024.