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| ID | Type | Description | Link |
|---|---|---|---|
| 2023-503837-23 | Other Identifier | EU Trial Number |
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This is a multiregional open-label extension (OLE) to assess the safety, tolerability, and efficacy of long-term treatment with tividenofusp alfa (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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A2 | Experimental | Participants with nMPS II, aged ≥5 to ≤10 years |
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| Cohort B2 | Experimental | Participants with nMPS II or nnMPS II, aged ≥1 to ≤18 years |
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| Cohort C2 | Experimental | Participants with nMPS II, aged <4 years |
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| Cohort D2 | Experimental | Participants with nMPS II or nnMPS II, aged ≤18 years with preexisting hepatomegaly who have never taken standard-of-care ERT |
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| Cohort E2 | Experimental | 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 |
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| Cohort A7 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tividenofusp alfa | Drug | Intravenous repeating dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence and intensity of treatment-emergent adverse events (TEAEs) | 5 years | |
| Clinically significant changes in urine total glycosaminoglycan (GAG) concentrations throughout the treatment period | 5 years | |
| 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. | 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration | 5 years | |
| Change from baseline in the Vineland-3 Adaptive Behavior Scale | 5 years | |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Denali Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Benioff Children's Hospital Oakland | Oakland | California | 94609 | United States | ||
| Ann and Robert H Lurie Children's Hospital of Chicago |
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| Label | URL |
|---|---|
| Denali Therapeutics | View source |
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Participants with nMPS II, aged ≥2 to <6 years |
|
| Cohort B7 | Experimental | Participants with nnMPS II, aged ≥6 to <17 years |
|
| Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) cognitive raw score |
| 5 years |
| Change from baseline in distance walked (meters) in the Six-Minute Walk Test (6MWT) | 5 years |
| Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations | 5 years |
| Liver volume within the normal range (normal vs abnormal) as measured by MRI | 5 years |
| Spleen volume within the normal range (normal vs abnormal) as measured by MRI | 5 years |
| Improvement in the Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II | 5 years |
| Chicago |
| Illinois |
| 60611 |
| United States |
| Hackensack University Medical Center | Hackensack | New Jersey | 07601 | United States |
| UNC Children's Research Institute | Chapel Hill | North Carolina | 27599 | United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| The University of Texas Medical School at Houston | Houston | Texas | 77030 | United States |
| Huntsman Cancer Hospital | Salt Lake City | Utah | 84112 | United States |
| Sanatorio Mater Dei | Buenos Aires | Argentina |
| Universitair Ziekenhuis Antwerpen | Edegem | Antwerpen | 2650 | Belgium |
| UZ Brussel | Jette | Belgium |
| University of Alberta - Faculty of Medicine & Dentistry | Edmonton | Alberta | Canada |
| Hospital for Sick Children | Toronto | Ontario | M5G 1X8 | Canada |
| McGill University Health Center | Montreal | Quebec | H4A3J1 | Canada |
| Vseobecna Fakultni Nemocnice V Praze | Prague | 120 00 | Czechia |
| Hopital Jeanne De Flandre - Metabolic Diseases Unit | Lille | France |
| Universitätsklinikum Hamburg-Eppendorf | Hamburg | Germany |
| SpinCS GmbH | Höchheim | Germany |
| ASST di Cremona | Cremona | Italy |
| Azienda Sanitaria Universitaria Friuli Centrale - PO Universitario Santa Maria della Misericordia | Udine | Italy |
| Erasmus Medical Center - Sophia Children's Hospital | Rotterdam | 3015 GD | Netherlands |
| Hospit U. Vall d'Hebron - PPDS | Barcelona | Spain |
| Drottning Silvias Barn Och Ungdomssjukhus | Gothenburg | Sweden |
| University Medical Faculty Balcali Hospital | Adana | Turkey (Türkiye) |
| Gazi Universitesi Tip Fakultes | Ankara | Turkey (Türkiye) |
| Birmingham Women's and Children's NHS Foundation Trust | Birmingham | United Kingdom |
| Royal Free Hospital | London | NW3 2QG | United Kingdom |
| Great Ormond Street Hospital | London | WC1N 3JH | United Kingdom |
| Royal Manchester Children's Hospital | Manchester | United Kingdom |
| ID | Term |
|---|---|
| D016532 | Mucopolysaccharidosis II |
| D013398 | Sudden Infant Death |
| ID | Term |
|---|---|
| D038901 | X-Linked Intellectual Disability |
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D009083 | Mucopolysaccharidoses |
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D017520 | Mucinoses |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D003645 | Death, Sudden |
| D003643 | Death |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D066088 | Infant Death |
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