A Study to Determine the Efficacy and Safety of Tividenofusp Alfa (DNL310) vs Idursulfase in Pediatric and Young Adult Participants With Neuronopathic (nMPS II) or Non-Neuronopathic Mucopolysaccharidosis Type II (nnMPS II)

Phase 3Active Not RecruitingNCT05371613

Denali Therapeutics Inc.65 enrolled

Overview

This is a Phase 2/3, multiregional, two-arm, double-blind, randomized, active (standard-of-care)-controlled study of the efficacy and safety of tividenofusp alfa (DNL310), an investigational central nervous system (CNS)-penetrant enzyme-replacement therapy (ERT) for mucopolysaccharidosis type II (MPS II). Participants may also qualify to enter an open-label treatment phase with DNL310 or idursulfase based on pre-specified criteria.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Mucopolysaccharidosis II

Interventions

tividenofusp alfaDRUG

Eligibility

Sex: ALLMin age: 2 YearsMax age: 25 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Participants aged ≥2 to \<6 years (Cohort A) or ≥6 to \<26 years (Cohort B) * Confirmed diagnosis of MPS II (for Cohort A, nMPS II; for Cohort B, nnMPS II) * Have no history of treatment with enzyme replacement therapy (ERT) OR not have received continuous ERT for 4 months prior to screening OR be on maintenance ERT and have tolerated idursulfase for a minimum of 4 months prior to screening Key Exclusion Criteria: * Have a documented mutation of other genes or genetic diagnosis accounting for developmental delay * Previously received an iduronate 2-sulfatase (IDS) gene therapy or stem cell therapy * Received any CNS-targeted MPS ERT within 6 months prior to screening * Have a contraindication for lumbar punctures and/or magnetic resonance imaging (MRI) * Participated in any other investigational drug study or used an investigational drug within 60 days prior to screening or intend to receive another investigational drug during the study

Locations (30)

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

Ann and Robert H Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

UNC Children's Research Institute

Chapel Hill, North Carolina, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Outcomes

Primary Outcomes

Ratio to baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (Cohort A)

Time frame: 24 weeks

Change from baseline in the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3)(Cohort A)

Time frame: 96 weeks

Secondary Outcomes

Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III)(Cohort A only)

Time frame: 96 weeks

Change from baseline in the Vineland-3 Adaptive Behavior Composite (ABC) score (Cohort A only)

Time frame: 96 weeks

Ratio to baseline in serum neurofilament light chain (NfL) (Cohort A only)

Time frame: 96 weeks

Change from baseline in distance walked in the Six-Minute Walk Test (6MWT; Cohort B only)

Time frame: 48 weeks

Ratio to baseline in the sum of urine HS and dermatan sulfate (DS) concentrations (normalized to creatinine) (Cohorts A and B)

Time frame: up to 48 weeks

Liver volume within the normal range (normal vs abnormal) as measured by magnetic resonance imaging (MRI) (Cohorts A and B)

Time frame: 48 weeks

Spleen volume within the normal range (normal vs abnormal) as measured by MRI (Cohorts A and B)

Time frame: 48 weeks

Improvement in Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II (Cohorts A and B)

Time frame: 48 weeks