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)

NCT ID: NCT05371613

Last Updated: 2025-08-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

63 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-21

Study Completion Date

2027-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Mucopolysaccharidosis II

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Cohort A: Participants with nMPS II

Group Type EXPERIMENTAL

tividenofusp alfa

Intervention Type DRUG

Intravenous repeating dose

idursulfase

Intervention Type DRUG

Intravenous repeating dose

Cohort B: Participants with nnMPS II

Group Type EXPERIMENTAL

tividenofusp alfa

Intervention Type DRUG

Intravenous repeating dose

idursulfase

Intervention Type DRUG

Intravenous repeating dose

Open-label Treatment Phase

Participants who meet pre-specified criteria may receive DNL310 or idursulfase

Group Type EXPERIMENTAL

tividenofusp alfa

Intervention Type DRUG

Intravenous repeating dose

idursulfase

Intervention Type DRUG

Intravenous repeating dose

Interventions

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tividenofusp alfa

Intravenous repeating dose

Intervention Type DRUG

idursulfase

Intravenous repeating dose

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

2 Years

Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Denali Therapeutics Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jose Alcantara Rodriguez, PharmD

Role: STUDY_DIRECTOR

Denali Therapeutics Inc.

Locations

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UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

Site Status RECRUITING

Ann and Robert H Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status RECRUITING

UNC Children's Research Institute

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

The University of Texas Medical School at Houston

Houston, Texas, United States

Site Status RECRUITING

University of Utah, PPDS

Salt Lake City, Utah, United States

Site Status RECRUITING

Sanatorio Mater Dei

Buenos Aires, , Argentina

Site Status RECRUITING

Women's and Children's Hospital

North Adelaide, , Australia

Site Status WITHDRAWN

UZ Antwerpen

Antwerp, Antwerpen, Belgium

Site Status RECRUITING

Universitair Ziekenhuis Brussel

Jette, Brussels Capital, Belgium

Site Status RECRUITING

Hospital de Clínicas de Porto Alegre (HCPA) - PPDS

Porto Alegre, , Brazil

Site Status RECRUITING

Instituto Fernandes Figueira

Rio de Janeiro, , Brazil

Site Status WITHDRAWN

University of Alberta - Faculty of Medicine & Dentistry

Edmonton, Alberta, Canada

Site Status RECRUITING

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status RECRUITING

McGill University Health Center

Montreal, Quebec, Canada

Site Status RECRUITING

Vseobecna Fakultni Nemocnice V Praze

Prague, , Czechia

Site Status RECRUITING

Hôpital Jeanne de Flandre

Lille, , France

Site Status RECRUITING

SphinCS

Höchheim, Hochheim, Germany

Site Status RECRUITING

Medizinische Universität Lausitz - Carl Thiem

Cottbus, , Germany

Site Status RECRUITING

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

Udine, , Italy

Site Status RECRUITING

Erasmus Medical Center - Sophia Children's Hospital

Rotterdam, Rotterdam, Netherlands

Site Status RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, Barcelona, Spain

Site Status RECRUITING

Hospital Infantil Universitario Niño Jesus

Madrid, Madrid, Spain

Site Status RECRUITING

Drottning Silvias Barn Och Ungdomssjukhus

Gothenburg, , Sweden

Site Status RECRUITING

Cukurova University Medical Faculty Balcali Hospital

Adana, , Turkey (Türkiye)

Site Status RECRUITING

Gazi Universitesi Tip Fakultesi

Çankaya, , Turkey (Türkiye)

Site Status RECRUITING

Great Ormond Street Hospital for Children

London, London, United Kingdom

Site Status RECRUITING

Birmingham Women's and Children's NHS Foundation Trust

Birmingham, , United Kingdom

Site Status RECRUITING

Royal Free Hospital

London, , United Kingdom

Site Status RECRUITING

Salford Royal Hospital

Salford, , United Kingdom

Site Status RECRUITING

Countries

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United States Argentina Australia Belgium Brazil Canada Czechia France Germany Italy Netherlands Spain Sweden Turkey (Türkiye) United Kingdom

Central Contacts

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Clinical Trials at Denali Therapeutics

Role: CONTACT

Facility Contacts

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Enrica Epifani

Role: primary

Dorine Heemskerk

Role: primary

Lucy Dougherty

Role: primary

Christina Calvo Patino

Role: primary

Emma Back

Role: primary

Fatma Derya Bulut

Role: primary

Yagmur Erdas

Role: primary

Christopher Jackson

Role: primary

Olivia Rosie-Wilkinson

Role: backup

Shashi Watson-Jones

Role: primary

Harprit Thakur

Role: backup

Bobie Boniface

Role: primary

Marie Meehan

Role: primary

Marissa Evans

Role: primary

Lindsey Lang

Role: primary

Role: backup

312-227-6712

Susan Mathus

Role: primary

Lindsay Torrice

Role: primary

Laurie Bailey

Role: primary

Genevieve Nesom

Role: primary

Marilyn Garcia

Role: primary

Carrie Bailey

Role: primary

Carolina Rojas

Role: primary

Tine Maes

Role: primary

Raquel Van den Eydne

Role: primary

Roberta Souto

Role: primary

Kathy Schellevis

Role: primary

Ashley Wilson

Role: primary

Christine Gannon

Role: primary

Patricia Deeb

Role: backup

Lenka Linkova

Role: primary

Amina Ziouche

Role: primary

Loreen Gramsch

Role: primary

Ms Loebel

Role: primary

Related Links

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Other Identifiers

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2024-510990-21-00

Identifier Type: CTIS

Identifier Source: secondary_id

2021-005200-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DNLI-E-0007

Identifier Type: -

Identifier Source: org_study_id

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