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

Mucopolysaccharidosis II Clinical Trial

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06075537
• Other study ID #: DNLI-E-0008
• Secondary ID: 2023-503837-23
• Status: Enrolling by invitation
• Phase: Phase 2/Phase 3
• Start date: September 20, 2023
• Est. completion date: June 2027

Study information

• Verified date: April 2024
• Source: Denali Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 99
• Est. completion date: June 2027
• Est. primary completion date: June 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Mucopolysaccharidoses
• Mucopolysaccharidosis II

Intervention

Drug:
• tividenofusp alfa
Intravenous repeating dose

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Antwerpen	Edegem	Antwerpen
Canada	Hospital for Sick Children	Toronto	Ontario
Czechia	Vseobecna Fakultni Nemocnice V Praze	Prague
Netherlands	Erasmus Medical Center - Sophia Children's Hospital	Rotterdam
United States	UNC Children's Research Institute	Chapel Hill	North Carolina
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Denali Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czechia,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and intensity of treatment-emergent adverse events (TEAEs)		5 years
Primary	Clinically significant changes in urine total glycosaminoglycan (GAG) concentrations throughout the treatment period		5 years
Primary	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.	5 years
Secondary	Percentage change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration		5 years
Secondary	Change from baseline in the Vineland-3 Adaptive Behavior Scale		5 years
Secondary	Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) cognitive raw score		5 years
Secondary	Change from baseline in distance walked (meters) in the Six-Minute Walk Test (6MWT)		5 years
Secondary	Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations		5 years
Secondary	Liver volume within the normal range (normal vs abnormal) as measured by MRI		5 years
Secondary	Spleen volume within the normal range (normal vs abnormal) as measured by MRI		5 years
Secondary	Improvement in the Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II		5 years

External Links

•   Engage Hunter Website