Clinical trial NCT05371613: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Mucopolysaccharidosis II
Keywords: Hunter Syndrome
MPS II
nMPS II
nnMPS II
Lead sponsor: Denali Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2022-05-12
Enrollment: 54
Sex: ALL
Minimum age (years): 2
Maximum age (years): 26
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percent change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (Cohort A)
timeFrame: 24 weeks
measure: Change from baseline in the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3)(Cohort A)
timeFrame: 96 weeks
Secondary outcomes:
measure: Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III)(Cohort A only)
timeFrame: 96 weeks
measure: Change from baseline in the Vineland-3 Adaptive Behavior Composite (ABC; Cohort A only)
timeFrame: 96 weeks
measure: Change from baseline in serum neurofilament light chain (NfL) (Cohort A only)
timeFrame: 96 weeks
measure: Change from baseline in distance walked in the Six-Minute Walk Test (6MWT; Cohort B only)
timeFrame: 48 weeks
measure: Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations (Cohorts A and B)
timeFrame: up to 48 weeks
measure: Liver volume within the normal range (normal vs abnormal) as measured by magnetic resonance imaging (MRI) (Cohorts A and B)
timeFrame: 48 weeks
measure: Spleen volume within the normal range (normal vs abnormal) as measured by MRI (Cohorts A and B)
timeFrame: 48 weeks
measure: Improvement in Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II (Cohorts A and B)
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: Chicago
country: United States
facility: Ann and Robert H Lurie Children's Hospital of Chicago
state: Illinois
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Chapel Hill
country: United States
facility: UNC Children's Research Institute
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas Medical School at Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah, PPDS
state: Utah
city: Buenos Aires
country: Argentina
facility: Sanatorio Mater Dei
city: North Adelaide
country: Australia
facility: Women's and Children's Hospital
city: Jette
country: Belgium
facility: Universitair Ziekenhuis Brussel
state: Brussels
city: Antwerpen
country: Belgium
facility: UZ Antwerpen
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre (HCPA) - PPDS
city: Rio De Janeiro
country: Brazil
facility: Instituto Fernandes Figueira
city: Edmonton
country: Canada
facility: University of Alberta - Faculty of Medicine & Dentistry
state: Alberta
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center
state: Quebec
city: Praha
country: Czechia
facility: Vseobecna Fakultni Nemocnice V Praze
city: Lille
country: France
facility: Hôpital Jeanne de Flandre
city: Cottbus
country: Germany
facility: Medizinische Universität Lausitz - Carl Thiem
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf
city: Hochheim
country: Germany
facility: SphinCS
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Friuli Centrale - PO Universitario Santa Maria della Misericordia
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center - Sophia Children's Hospital
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesus
city: Göteborg
country: Sweden
facility: Drottning Silvias Barn Och Ungdomssjukhus
city: Adana
country: Turkey
facility: Cukurova University Medical Faculty Balcali Hospital
city: Çankaya
country: Turkey
facility: Gazi Universitesi Tip Fakultesi
city: Birmingham
country: United Kingdom
facility: Birmingham Women's and Children's NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
city: Salford
country: United Kingdom
facility: Salford Royal Hospital
Study officials:
affiliation: Denali Therapeutics Inc.
name: Jose Alcantara Rodriguez, PharmD
role: STUDY_DIRECTOR
References: