Back to resultsAn Extension Study of the Long-Term Safety, Tolerability, and Efficacy of DNL310 in Participants With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007
Primary Purpose
Mucopolysaccharidosis II
Status
Enrolling by invitation
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
DNL310
Sponsored by
About this trial
This is an interventional treatment trial for Mucopolysaccharidosis II focused on measuring Hunter Syndrome, MPS II, nMPS II, nnMPS II
Eligibility Criteria
Key Inclusion Criteria: For participants from Study DNLI-E-0002 only: Completed at least through the Week 49 visit in Study DNLI-E-0002 and did not discontinue study intervention early For participants from Study DNLI-E-0007 only: Completed the treatment period of 96 weeks in Cohort A for nMPS II participants and 48 weeks in Cohort B for nnMPS II participants Key Exclusion Criteria: Unstable or poorly controlled medical condition(s) or significant medical or psychological comorbidity or comorbidities that, in the opinion of the investigator, would interfere with safe participation in the trial or interpretation of study assessments
Sites / Locations
- Cincinnati Children's Hospital Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort A2
Cohort B2
Cohort C2
Cohort D2
Cohort E2
Cohort A7
Cohort B7
Arm Description
Participants with nMPS II, aged ≥5 to ≤10 years
Participants with nMPS II or nnMPS II, aged ≥1 to ≤18 years
Participants with nMPS II, aged <4 years
Participants with nMPS II or nnMPS II, aged ≤18 years with preexisting hepatomegaly who have never taken standard-of-care ERT
Participants with nMPS II, aged ≥6 years; participants with nnMPS II, aged <6 or ≥17 years; or participants with nMPS II, aged ≥1 to ≤18 years, with a history of prior HSCT or gene therapy and have completed at least 48 weeks in Study DNLI-E-0001
Participants with nMPS II, aged ≥2 to <6 years
Participants with nnMPS II, aged ≥6 to <17 years
Outcomes
Primary Outcome Measures
Incidence and intensity of treatment-emergent adverse events (TEAEs)
Clinically significant changes in urine total glycosaminoglycan (GAG) concentrations throughout the treatment period
Incidence and intensity of infusion-related reactions (IRRs)
The intensity of IRRs will be assessed following each infusion of DNL310 using the categories of Mild, Moderate and Severe. IRRs will be summarized overall as well as stratified by intensity.
Secondary Outcome Measures
Percentage change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration
Change from baseline in the Vineland-3 Adaptive Behavior Scale
Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) cognitive raw score
Change from baseline in distance walked (meters) in the Six-Minute Walk Test (6MWT)
Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations
Liver volume within the normal range (normal vs abnormal) as measured by MRI
Spleen volume within the normal range (normal vs abnormal) as measured by MRI
Improvement in the Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II
Full Information
NCT ID
NCT06075537
First Posted
September 18, 2023
Last Updated
October 10, 2023
Sponsor
Denali Therapeutics Inc.
1. Study Identification
Unique Protocol Identification Number
NCT06075537
Brief Title
An Extension Study of the Long-Term Safety, Tolerability, and Efficacy of DNL310 in Participants With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007
Official Title
An Open-Label Extension to Investigate the Long-Term Safety, Tolerability, and Efficacy of DNL310 in Patients With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
September 20, 2023 (Actual)
Primary Completion Date
June 2027 (Anticipated)
Study Completion Date
June 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Denali Therapeutics Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a multiregional open-label extension (OLE) to assess the safety, tolerability, and efficacy of long-term treatment with DNL310, an investigational central nervous system (CNS)-penetrant intravenous (IV) enzyme replacement therapy (ERT) for Hunter syndrome (MPS II). Participants who complete at least through the Week 49 visit in Study DNLI-E-0002 and do not discontinue study intervention early and participants who complete Study DNLI-E-0007 will be enrolled in this OLE. All participants will receive DNL310 for up to 5 years from the time of entry in this OLE. Participants, site staff, and the Sponsor will remain blinded to the original treatment assignment for participants entering this OLE from Study DNLI-E-0007.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mucopolysaccharidosis II
Keywords
Hunter Syndrome, MPS II, nMPS II, nnMPS II
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
99 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cohort A2
Arm Type
Experimental
Arm Description
Participants with nMPS II, aged ≥5 to ≤10 years
Arm Title
Cohort B2
Arm Type
Experimental
Arm Description
Participants with nMPS II or nnMPS II, aged ≥1 to ≤18 years
Arm Title
Cohort C2
Arm Type
Experimental
Arm Description
Participants with nMPS II, aged <4 years
Arm Title
Cohort D2
Arm Type
Experimental
Arm Description
Participants with nMPS II or nnMPS II, aged ≤18 years with preexisting hepatomegaly who have never taken standard-of-care ERT
Arm Title
Cohort E2
Arm Type
Experimental
Arm Description
Participants with nMPS II, aged ≥6 years; participants with nnMPS II, aged <6 or ≥17 years; or participants with nMPS II, aged ≥1 to ≤18 years, with a history of prior HSCT or gene therapy and have completed at least 48 weeks in Study DNLI-E-0001
Arm Title
Cohort A7
Arm Type
Experimental
Arm Description
Participants with nMPS II, aged ≥2 to <6 years
Arm Title
Cohort B7
Arm Type
Experimental
Arm Description
Participants with nnMPS II, aged ≥6 to <17 years
Intervention Type
Drug
Intervention Name(s)
DNL310
Intervention Description
Intravenous repeating dose
Primary Outcome Measure Information:
Title
Incidence and intensity of treatment-emergent adverse events (TEAEs)
Time Frame
5 years
Title
Clinically significant changes in urine total glycosaminoglycan (GAG) concentrations throughout the treatment period
Time Frame
5 years
Title
Incidence and intensity of infusion-related reactions (IRRs)
Description
The intensity of IRRs will be assessed following each infusion of DNL310 using the categories of Mild, Moderate and Severe. IRRs will be summarized overall as well as stratified by intensity.
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Percentage change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration
Time Frame
5 years
Title
Change from baseline in the Vineland-3 Adaptive Behavior Scale
Time Frame
5 years
Title
Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) cognitive raw score
Time Frame
5 years
Title
Change from baseline in distance walked (meters) in the Six-Minute Walk Test (6MWT)
Time Frame
5 years
Title
Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations
Time Frame
5 years
Title
Liver volume within the normal range (normal vs abnormal) as measured by MRI
Time Frame
5 years
Title
Spleen volume within the normal range (normal vs abnormal) as measured by MRI
Time Frame
5 years
Title
Improvement in the Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II
Time Frame
5 years
10. Eligibility
Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
For participants from Study DNLI-E-0002 only: Completed at least through the Week 49 visit in Study DNLI-E-0002 and did not discontinue study intervention early
For participants from Study DNLI-E-0007 only: Completed the treatment period of 96 weeks in Cohort A for nMPS II participants and 48 weeks in Cohort B for nnMPS II participants
Key Exclusion Criteria:
Unstable or poorly controlled medical condition(s) or significant medical or psychological comorbidity or comorbidities that, in the opinion of the investigator, would interfere with safe participation in the trial or interpretation of study assessments
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jose Alcantara Rodriguez, PharmD
Organizational Affiliation
Denali Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://www.engagehunter.com/clinical-trials
Description
Engage Hunter Website
Learn more about this trial
An Extension Study of the Long-Term Safety, Tolerability, and Efficacy of DNL310 in Participants With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007
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