RecruitingPhase 2Phase 3NCT05371613

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)

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


Sponsor

Denali Therapeutics Inc.

Enrollment

63 participants

Start Date

Jul 21, 2022

Study Type

INTERVENTIONAL

Conditions

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

Min Age: 2 YearsMax Age: 25 Years

Inclusion Criteria3

  • 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 Criteria5

  • 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

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Interventions

DRUGtividenofusp alfa

Intravenous repeating dose

DRUGidursulfase

Intravenous repeating dose


Locations(32)

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

Ann and Robert H Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

UNC Children's Research Institute

Chapel Hill, North Carolina, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

The University of Texas Medical School at Houston

Houston, Texas, United States

University of Utah, PPDS

Salt Lake City, Utah, United States

Sanatorio Mater Dei

Buenos Aires, Argentina

Women's and Children's Hospital

North Adelaide, Australia

UZ Antwerpen

Antwerp, Antwerpen, Belgium

Universitair Ziekenhuis Brussel

Jette, Brussels Capital, Belgium

Hospital de Clínicas de Porto Alegre (HCPA) - PPDS

Porto Alegre, Brazil

Instituto Fernandes Figueira

Rio de Janeiro, Brazil

University of Alberta - Faculty of Medicine & Dentistry

Edmonton, Alberta, Canada

Hospital for Sick Children

Toronto, Ontario, Canada

McGill University Health Center

Montreal, Quebec, Canada

Vseobecna Fakultni Nemocnice V Praze

Prague, Czechia

Hôpital Jeanne de Flandre

Lille, France

SphinCS

Höchheim, Hochheim, Germany

Medizinische Universität Lausitz - Carl Thiem

Cottbus, Germany

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

Udine, Italy

Erasmus Medical Center - Sophia Children's Hospital

Rotterdam, Rotterdam, Netherlands

Hospital Universitario Vall d'Hebron

Barcelona, Barcelona, Spain

Hospital Infantil Universitario Niño Jesus

Madrid, Madrid, Spain

Drottning Silvias Barn Och Ungdomssjukhus

Gothenburg, Sweden

Cukurova University Medical Faculty Balcali Hospital

Adana, Turkey (Türkiye)

Gazi Universitesi Tip Fakultesi

Çankaya, Turkey (Türkiye)

Great Ormond Street Hospital for Children

London, London, United Kingdom

Birmingham Women's and Children's NHS Foundation Trust

Birmingham, United Kingdom

Royal Free Hospital

London, United Kingdom

Salford Royal Hospital

Salford, United Kingdom

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NCT05371613


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