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 3Enrolling By InvitationNCT06075537

Denali Therapeutics Inc.99 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Mucopolysaccharidosis II

Interventions

Eligibility

Sex: ALLMax age: 18 Years

Medical Language ↔ Plain English

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

Locations (22)

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

UNC Children's Research Institute

Chapel Hill, North Carolina, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

The University of Texas Medical School at Houston

Houston, Texas, United States

Huntsman Cancer Hospital

Salt Lake City, Utah, United States

Sanatorio Mater Dei

Buenos Aires, Argentina

Universitair Ziekenhuis Antwerpen

Edegem, Antwerpen, Belgium

UZ Brussel

Jette, Belgium

University of Alberta - Faculty of Medicine & Dentistry

Edmonton, Alberta, Canada

...and 12 more locations

Outcomes

Primary Outcomes

Incidence and intensity of treatment-emergent adverse events (TEAEs)

Time frame: 5 years

Clinically significant changes in urine total glycosaminoglycan (GAG) concentrations throughout the treatment period

Time frame: 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.

Time frame: 5 years

Secondary Outcomes

Percentage change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration

Time frame: 5 years

Change from baseline in the Vineland-3 Adaptive Behavior Scale

Time frame: 5 years

Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) cognitive raw score

Time frame: 5 years

Change from baseline in distance walked (meters) in the Six-Minute Walk Test (6MWT)

Time frame: 5 years

Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations

Time frame: 5 years

Liver volume within the normal range (normal vs abnormal) as measured by MRI

Time frame: 5 years

Spleen volume within the normal range (normal vs abnormal) as measured by MRI

Time frame: 5 years

Improvement in the Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II

Time frame: 5 years