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

Phase 2

• Conditions: Mucopolysaccharidosis II
• Interventions: Drug: tividenofusp alfa

• Registration Number: NCT06075537
• Lead Sponsor: Denali Therapeutics Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-09-18
• Study Start: 2023-09-20
• Study First Submitted QC: 2023-10-03
• Study First Posted: 2023-10-10
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-20
• Last Update Posted: 2024-12-27
• Primary Completion: 2027-06
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 99

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort B7	tividenofusp alfa	Participants with nnMPS II, aged ≥6 to \<17 years
Cohort B2	tividenofusp alfa	Participants with nMPS II or nnMPS II, aged ≥1 to ≤18 years
Cohort A2	tividenofusp alfa	Participants with nMPS II, aged ≥5 to ≤10 years
Cohort E2	tividenofusp alfa	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
Cohort C2	tividenofusp alfa	Participants with nMPS II, aged \<4 years
Cohort D2	tividenofusp alfa	Participants with nMPS II or nnMPS II, aged ≤18 years with preexisting hepatomegaly who have never taken standard-of-care ERT
Cohort A7	tividenofusp alfa	Participants with nMPS II, aged ≥2 to \<6 years

Primary Outcome Measures

Name	Time	Method
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)	5 years	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

Name	Time	Method
Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) cognitive raw score	5 years
Percentage change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration	5 years
Liver volume within the normal range (normal vs abnormal) as measured by MRI	5 years
Change from baseline in the Vineland-3 Adaptive Behavior Scale	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
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

Trial Locations

Locations (9)

Hopital Jeanne De Flandre - Metabolic Diseases Unit; 🇫🇷 Lille, France

Hospit U. Vall d'Hebron - PPDS; 🇪🇸 Barcelona, Spain

UZ Brussel; 🇧🇪 Jette, Belgium

UNC Children's Research Institute; 🇺🇸 Chapel Hill, North Carolina, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Universitair Ziekenhuis Antwerpen; 🇧🇪 Edegem, Antwerpen, Belgium

Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada

Vseobecna Fakultni Nemocnice V Praze; 🇨🇿 Prague, Czechia

Erasmus Medical Center - Sophia Children's Hospital; 🇳🇱 Rotterdam, Netherlands