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)

Official title

A Phase 2/3, Multicenter, Double-Blind, Randomized Study to Determine the Efficacy and Safety of Tividenofusp Alfa (DNL310) vs Idursulfase in Pediatric and Young Adult Participants With Neuronopathic or Non-Neuronopathic Mucopolysaccharidosis Type II

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.

Interventions

• Drug tividenofusp alfa
  Intravenous repeating dose
• Drug idursulfase
  Intravenous repeating dose

Primary outcome measures

• Percent change from 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 outcome measures (8)

• 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; Cohort A only) [Time frame: 96 weeks]
• Change from 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]
• Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations (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]

Eligibility criteria

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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 8 centers

• UCSF Benioff Children's Hospital Oakland — Oakland
• Ann and Robert H Lurie Children's Hospital of Chicago — Chicago
• Hackensack University Medical Center — Hackensack
• UNC Children's Research Institute — Chapel Hill
• Cincinnati Children's Hospital Medical Center — Cincinnati
• Children's Hospital of Philadelphia — Philadelphia
• The University of Texas Medical School at Houston — Houston
• University of Utah, PPDS — Salt Lake City

United Kingdom · 4 centers

• Great Ormond Street Hospital for Children — London
• Birmingham Women's and Children's NHS Foundation Trust — Birmingham
• Royal Free Hospital — London
• Salford Royal Hospital — Salford

Canada · 3 centers

• University of Alberta - Faculty of Medicine & Dentistry — Edmonton
• Hospital for Sick Children — Toronto
• McGill University Health Center — Montreal

Belgium · 2 centers

• UZ Antwerpen — Antwerp
• Universitair Ziekenhuis Brussel — Jette

Brazil · 2 centers

• Hospital de Clínicas de Porto Alegre (HCPA) - PPDS — Porto Alegre
• Instituto Fernandes Figueira — Rio de Janeiro

Germany · 2 centers

• SphinCS — Höchheim
• Medizinische Universität Lausitz - Carl Thiem — Cottbus

Spain · 2 centers

• Hospital Universitario Vall d'Hebron — Barcelona
• Hospital Infantil Universitario Niño Jesus — Madrid

Turkey (Türkiye) · 2 centers

• Cukurova University Medical Faculty Balcali Hospital — Adana
• Gazi Universitesi Tip Fakultesi — Çankaya

Argentina · 1 center

• Sanatorio Mater Dei — Buenos Aires

Australia · 1 center

• Women's and Children's Hospital — North Adelaide

Czechia · 1 center

• Vseobecna Fakultni Nemocnice V Praze — Prague

France · 1 center

• Hôpital Jeanne de Flandre — Lille

Italy · 1 center

• Azienda Sanitaria Universitaria Friuli Centrale - PO Universitario Santa Maria della Miser — Udine

Netherlands · 1 center

• Erasmus Medical Center - Sophia Children's Hospital — Rotterdam

Sweden · 1 center

• Drottning Silvias Barn Och Ungdomssjukhus — Gothenburg

Identifiers

NCT: NCT05371613 · DNLI-E-0007 · 2024-510990-21-00 · 2021-005200-35

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗