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

NCT06075537 | Enrolling By Invitation Phase 2 DMC FDA Drug

• 2 other identifiers: DNLI-E-00082023-503837-23
• Study Type: interventional
• Target: 99
• Locations: 13 countries
• Sites: 26

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.

Conditions

Mucopolysaccharidosis II

Keywords

Hunter Syndrome; MPS II; nMPS II; nnMPS II

Outcome Measures

Primary Outcomes (3)

• Incidence and intensity of treatment-emergent adverse events (TEAEs)

  5 years

• Clinically significant changes in urine total glycosaminoglycan (GAG) concentrations throughout the treatment period

  5 years

• 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 Outcomes (8)

• Percentage change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration

  5 years

• Change from baseline in the Vineland-3 Adaptive Behavior Scale

  5 years

• Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) cognitive raw score

  5 years

• Change from baseline in distance walked (meters) in the Six-Minute Walk Test (6MWT)

  5 years

• Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations

  5 years

Study Arms (7)

Cohort A2

EXPERIMENTAL

Participants with nMPS II, aged ≥5 to ≤10 years

Drug: tividenofusp alfa

Cohort B2

EXPERIMENTAL

Participants with nMPS II or nnMPS II, aged ≥1 to ≤18 years

Drug: tividenofusp alfa

Cohort C2

EXPERIMENTAL

Participants with nMPS II, aged \<4 years

Drug: tividenofusp alfa

Cohort D2

EXPERIMENTAL

Participants with nMPS II or nnMPS II, aged ≤18 years with preexisting hepatomegaly who have never taken standard-of-care ERT

Drug: tividenofusp alfa

Cohort E2

EXPERIMENTAL

Participants with nMPS II, aged ≥6 years; participants with nnMPS II, aged \<6 or ≥17 years; or participants with nMPS II, aged ≥1 to ≤18 years, with a history of prior HSCT or gene therapy and have completed at least 48 weeks in Study DNLI-E-0001

Drug: tividenofusp alfa

Cohort A7

EXPERIMENTAL

Participants with nMPS II, aged ≥2 to \<6 years

Drug: tividenofusp alfa

Cohort B7

EXPERIMENTAL

Participants with nnMPS II, aged ≥6 to \<17 years

Drug: tividenofusp alfa

Interventions

tividenofusp alfa DRUG

Intravenous repeating dose

Cohort A2; Cohort A7; Cohort B2; Cohort B7; Cohort C2; Cohort D2; Cohort E2

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Denali Therapeutics Inc.: lead

Study Sites (26)

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

UNC Children's Research Institute

Chapel Hill, North Carolina, 27599, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

The University of Texas Medical School at Houston

Houston, Texas, 77030, United States

Location

Huntsman Cancer Hospital

Salt Lake City, Utah, 84112, United States

Location

Sanatorio Mater Dei

Buenos Aires, Argentina

Location

Universitair Ziekenhuis Antwerpen

Edegem, Antwerpen, 2650, Belgium

Location

UZ Brussel

Jette, Belgium

Location

University of Alberta - Faculty of Medicine & Dentistry

Edmonton, Alberta, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

McGill University Health Center

Montreal, Quebec, H4A3J1, Canada

Location

Vseobecna Fakultni Nemocnice V Praze

Prague, 120 00, Czechia

Location

Hopital Jeanne De Flandre - Metabolic Diseases Unit

Lille, France

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, Germany

Location

SpinCS GmbH

Höchheim, Germany

Location

ASST di Cremona

Cremona, Italy

Location

Azienda Sanitaria Universitaria Friuli Centrale - PO Universitario Santa Maria della Misericordia

Udine, Italy

Location

Erasmus Medical Center - Sophia Children's Hospital

Rotterdam, 3015 GD, Netherlands

Location

Hospit U. Vall d'Hebron - PPDS

Barcelona, Spain

Location

Drottning Silvias Barn Och Ungdomssjukhus

Gothenburg, Sweden

Location

University Medical Faculty Balcali Hospital

Adana, Turkey (Türkiye)

Location

Gazi Universitesi Tip Fakultes

Ankara, Turkey (Türkiye)

Location

Birmingham Women's and Children's NHS Foundation Trust

Birmingham, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

Location

Related Links

• Denali Therapeutics

MeSH Terms

Conditions

Mucopolysaccharidosis II; Sudden Infant Death

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infant Death

Study Officials

• Medical Monitor

  Denali Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2023
• First Posted: October 10, 2023
• Study Start: September 20, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

TU (2); US (6); ES (1); AR (1); CZ (1); CA (3); IT (2); BE (2); NL (1); SE (1); GB (3); DE (2); FR (1)