An Extension Study of the Long-Term Safety, Tolerability, and Efficacy of Tividenofusp Alfa (DNL310) in Participants With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Mucopolysaccharidosis II

Intervention / Treatment
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* Drug: tividenofusp alfa


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A2<br>Participants with nMPS II, aged ≥5 to ≤10 years | Drug: tividenofusp alfa<br>* Intravenous repeating dose<br>|
| Experimental: Cohort B2<br>Participants with nMPS II or nnMPS II, aged ≥1 to ≤18 years | Drug: tividenofusp alfa<br>* Intravenous repeating dose<br>|
| Experimental: Cohort C2<br>Participants with nMPS II, aged <4 years | Drug: tividenofusp alfa<br>* Intravenous repeating dose<br>|
| Experimental: Cohort D2<br>Participants with nMPS II or nnMPS II, aged ≤18 years with preexisting hepatomegaly who have never taken standard-of-care ERT | Drug: tividenofusp alfa<br>* Intravenous repeating dose<br>|
| Experimental: Cohort E2<br>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 | Drug: tividenofusp alfa<br>* Intravenous repeating dose<br>|
| Experimental: Cohort A7<br>Participants with nMPS II, aged ≥2 to <6 years | Drug: tividenofusp alfa<br>* Intravenous repeating dose<br>|
| Experimental: Cohort B7<br>Participants with nnMPS II, aged ≥6 to <17 years | Drug: tividenofusp alfa<br>* Intravenous repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hunter Syndrome, MPS II, nMPS II, nnMPS II