Clinical trial NCT06075537: 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
Official title: An Open-Label Extension to Investigate the Long-Term Safety, Tolerability, and Efficacy of DNL310 in Patients With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
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: 2023-10-10
Enrollment: 99
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence and intensity of treatment-emergent adverse events (TEAEs)
timeFrame: 5 years
measure: Clinically significant changes in urine total glycosaminoglycan (GAG) concentrations throughout the treatment period
timeFrame: 5 years
measure: Incidence and intensity of infusion-related reactions (IRRs)
timeFrame: 5 years
Secondary outcomes:
measure: Percentage change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration
timeFrame: 5 years
measure: Change from baseline in the Vineland-3 Adaptive Behavior Scale
timeFrame: 5 years
measure: Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) cognitive raw score
timeFrame: 5 years
measure: Change from baseline in distance walked (meters) in the Six-Minute Walk Test (6MWT)
timeFrame: 5 years
measure: Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations
timeFrame: 5 years
measure: Liver volume within the normal range (normal vs abnormal) as measured by MRI
timeFrame: 5 years
measure: Spleen volume within the normal range (normal vs abnormal) as measured by MRI
timeFrame: 5 years
measure: Improvement in the Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II
timeFrame: 5 years
Other outcomes:
Locations:
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: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
state: Antwerpen
city: Jette
country: Belgium
facility: UZ Brussel
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Center
city: Prague
country: Czechia
facility: Vseobecna Fakultni Nemocnice V Praze
city: Lille
country: France
facility: Hopital Jeanne De Flandre - Metabolic Diseases Unit
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hochheim
country: Germany
facility: SpinCS GmbH
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center - Sophia Children's Hospital
city: Barcelona
country: Spain
facility: Hospit U. Vall d'Hebron - PPDS
Study officials:
affiliation: Denali Therapeutics
name: Jose Alcantara Rodriguez, PharmD
role: STUDY_DIRECTOR
References: