- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05371613
A Study to Determine the Efficacy and Safety of Tividenofusp Alfa (DNL310) vs Idursulfase in Pediatric Participants With Neuronopathic (nMPS II) or Non-Neuronopathic Mucopolysaccharidosis Type II (nnMPS II) (COMPASS)
A Phase 2/3, Multicenter, Double-Blind, Randomized Study to Determine the Efficacy and Safety of DNL310 vs Idursulfase in Pediatric Participants With Neuronopathic or Non-Neuronopathic Mucopolysaccharidosis Type II
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Contact
- Name: Clinical Trials at Denali Therapeutics
- Email: clinical-trials@dnli.com
Study Locations
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Buenos Aires, Argentina, C1199ABB
- Recruiting
- Hospital Italiano de Buenos Aires
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Contact:
- Sabina Garcia
- Email: sabinagarcia@iadin.com.ar
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Principal Investigator:
- Javier Muntadas Rausei, MD
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Buenos Aires, Argentina
- Recruiting
- Sanatorio Mater Dei
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Contact:
- Carolina Rojas
- Email: crojas@fundacionrespirar.org
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Principal Investigator:
- Alejandro Fainboim, MD
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Antwerpen, Belgium, 2650
- Recruiting
- UZ Antwerpen
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Contact:
- Tine Maes
- Email: tine.maes@uza.be
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Principal Investigator:
- Francois Eyskens, MD
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Brussels
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Jette, Brussels, Belgium, 1090
- Recruiting
- Universitair Ziekenhuis Brussel
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Contact:
- Raquel Van den Eydne
- Email: Raquel.VanDenEynde@uzbrussel.be
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Principal Investigator:
- Luc Regal, MD
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Alberta
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Edmonton, Alberta, Canada
- Recruiting
- University of Alberta - Faculty of Medicine & Dentistry
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Contact:
- Farah Hassan
- Email: farah.hassan@albertahealthservices.ca
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Principal Investigator:
- Saadet Andrews, MD
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Ontario
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Toronto, Ontario, Canada, M5G1X8
- Recruiting
- Hospital for Sick Children
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Contact:
- Preet Dhillon
- Email: preet.dhillon@sickkids.ca
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Principal Investigator:
- Michal Inbar-Feigenberg, MD
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Quebec
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Montreal, Quebec, Canada, H4A3J1
- Recruiting
- McGill University Health Center
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Principal Investigator:
- John Mitchell, MD
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Contact:
- Christine Gannon
- Email: christine.gannon@muhc.mcgill.ca
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Contact:
- Patricia Deeb
- Email: patricia.deeb@muhc.mcgill.ca
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Bogotá, Colombia
- Recruiting
- Fundación Cardioinfantil Instituto Cardiológico
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Principal Investigator:
- Martha Solano, MD
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Contact:
- Astrid Yohana
- Email: asgomez@lacardio.org
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Praha, Czechia, 128 08
- Recruiting
- Vseobecna fakultni nemocnice v Praze
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Contact:
- Lenka Linkova
- Email: lenka.linkova@vfn.cz
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Principal Investigator:
- Martin Magner, MD
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Lille, France, 59000
- Recruiting
- Hôpital Jeanne de Flandre
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Principal Investigator:
- Anne-Sophie Guémann, MD
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Contact:
- Amina Ziouche
- Email: amina.ziouche@chru-lillie.fr
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Marseille, France, 13385
- Recruiting
- Hopitaux de La Timone
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Contact:
- Murielle Champeaux
- Email: murielle.champeaux@ap-hm.fr
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Principal Investigator:
- Brigitte Chabrol, MD
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Toulouse, France
- Recruiting
- CHU Toulouse
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Principal Investigator:
- Aurélie Bourchany, MD
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Contact:
- Emilie Hervier
- Email: hervier.e@chu-toulouse.fr
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Hamburg, Germany, 20251
- Recruiting
- Universitatsklinikum Hamburg Eppendorf
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Principal Investigator:
- Nicole Muschol, MD
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Contact:
- Katharina Trepner
- Email: icld@uke.de
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Hochheim, Germany, 65239
- Recruiting
- SphinCS
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Contact:
- Loreen Gramsch
- Email: loreen.gramsch@sphincs.de
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Principal Investigator:
- Eugen Mengel, MD
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Napoli, Italy, 80131
- Recruiting
- Azienda Ospedaliera Universitaria Federico II
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Contact:
- Margherita Dell'Anno
- Email: m.dellanno@tigem.it
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Principal Investigator:
- Giancarlo Parenti, MD
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Udine, Italy, 33100
- Recruiting
- Azienda Sanitaria Universitaria Friuli Centrale - PO Universitario Santa Maria della Misericordia
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Principal Investigator:
- Maurizio Scarpa, MD
-
Contact:
- Enrica Epifani
- Email: enrica.epifani@asufc.sanita.fvg.it
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Rotterdam, Netherlands, 3000
- Recruiting
- Erasmus Medical Center - Sophia Children's Hospital
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Contact:
- Dorine Heemskerk
- Email: t.heemskerk@erasmusmc.nl
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Principal Investigator:
- Hannerieke van den Hout, MD
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A Coruña, Spain, 15706
- Recruiting
- Hospital Clinico Universitario de Santiago
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Contact:
- Roi Chans Gerpe
- Email: roi.chans.gerpe@sergas.es
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Principal Investigator:
- Maria Luz Couce Pico, MD
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Barcelona, Spain, 08035
- Recruiting
- Hospital Universitario Vall d'Hebron
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Principal Investigator:
- Mireia del Toro, MD
-
Contact:
- Lucy Dougherty
- Email: lucy.dougherty@vhir.org
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Madrid, Spain, 28009
- Recruiting
- Hospital Infantil Universitario Nino Jesus
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Principal Investigator:
- Laura Lopez Marin, MD
-
Contact:
- Christina Calvo Patino
- Email: ccpatino@salud.madrid.org
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Göteborg, Sweden, 416 85
- Recruiting
- Drottning Silvias Barn Och Ungdomssjukhus
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Principal Investigator:
- Niklas Darin, MD, PhD
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Contact:
- Emma Back
- Email: emma.back@vgregion.se
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Adana, Turkey, 1330
- Recruiting
- Cukurova University Medical Faculty Balcali Hospital
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Contact:
- Nurşah Gulseren
- Email: nursahgulseren523@hotmail.com
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Principal Investigator:
- Neslihan Mungan, MD
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Çankaya, Turkey, 06500
- Recruiting
- Gazi Universitesi Tip Fakultesi
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Contact:
- Gozde Dulgar
- Email: gozde.dulgar@medex-smo.com
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Principal Investigator:
- Faith Ezgu, MD
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Birmingham, United Kingdom
- Recruiting
- Birmingham Women's and Children's NHS Foundation Trust
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Principal Investigator:
- Julian Raiman, MD
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Contact:
- Shashi Watson-Jones
- Email: shashi.rana@nhs.net
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Contact:
- Harprit Thakur
- Email: harprit.thakur@nhs.net
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London, United Kingdom, WC1N 3JH
- Recruiting
- Great Ormond Street Hospital for Children
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Contact:
- Kerry Gilroy
- Email: kerry.gilroy@gosh.nhs.uk
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Contact:
- Olivia Rosie-Wilkinson
- Email: Olivia.Rosie-Wilkinson@gosh.nhs.uk
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Principal Investigator:
- Spyros Batzios, MD
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California
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Oakland, California, United States, 94609
- Recruiting
- UCSF Benioff Children's Hospital Oakland
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Principal Investigator:
- Paul Harmatz, MD
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Contact:
- Marissa Evans
- Email: Marissa.Evans@ucsf.edu
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Georgia
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Atlanta, Georgia, United States, 30322
- Recruiting
- Emory University
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Principal Investigator:
- William Wilcox, MD
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Contact:
- Gwendolyn Gunn
- Email: gwendolyn.gisiner.gunn@emory.edu
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Illinois
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Chicago, Illinois, United States, 60611
- Recruiting
- Ann and Robert H Lurie Children's Hospital of Chicago
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Principal Investigator:
- Barbara Burton, MD
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Contact:
- Lindsey Lang
- Email: llang@luriechildrens.org
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Contact:
- Phone Number: 312-227-6712
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New Jersey
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Hackensack, New Jersey, United States, 07601
- Recruiting
- Hackensack University Medical Center
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Contact:
- Susan Mathus
- Email: susan.mathus@hmhn.org
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Principal Investigator:
- Helio Pedro, MD
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North Carolina
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Chapel Hill, North Carolina, United States, 27514
- Recruiting
- UNC Children's Research Institute
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Principal Investigator:
- Joseph Muenzer, MD
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Contact:
- Heather Press
- Email: heather_preiss@med.unc.edu
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Ohio
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Cincinnati, Ohio, United States, 45229
- Recruiting
- Cincinnati Children's Hospital Medical Center
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Contact:
- Connie Wehmeyer
- Phone Number: 513-636-4760
- Email: connie.wehmeyer@cchmc.org
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Principal Investigator:
- Nancy Leslie, MD
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Recruiting
- Children's Hospital of Philadelphia
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Principal Investigator:
- Can Ficicioglu, MD
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Contact:
- Henry Daumeyer
- Email: daumeyerh@chop.edu
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Pittsburgh, Pennsylvania, United States, 15224
- Recruiting
- Children's Hospital of Pittsburgh
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Contact:
- Dawn Kolar
- Email: kolardr@upmc.edu
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Principal Investigator:
- Deepa Rajan, MD
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Texas
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Houston, Texas, United States, 77030
- Recruiting
- The University of Texas Medical School at Houston
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Principal Investigator:
- Paul Hillman, MD
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Contact:
- Marilyn Garcia
- Email: marilyn.garcia@uth.tmc.edu
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Utah
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Salt Lake City, Utah, United States, 84132
- Recruiting
- University of Utah, PPDS
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Contact:
- Carrie Bailey
- Email: carrie.bailey@hsc.utah.edu
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Principal Investigator:
- David Viskochil, MD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Key Inclusion Criteria:
- Participants aged ≥2 to <6 years (Cohort A) or ≥6 to <17 years (Cohort B)
- Confirmed diagnosis of MPS II (for Cohort A, nMPS II; for Cohort B, nnMPS II)
- Be on maintenance enzyme replacement therapy (ERT) and have tolerated idursulfase for a minimum of 4 months prior to screening
Key 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 imagings (MRIs)
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort A: Participants with nMPS II
|
Intravenous repeating dose
Intravenous repeating dose
|
Experimental: Cohort B: Participants with nnMPS II
|
Intravenous repeating dose
Intravenous repeating dose
|
Experimental: Open-label Treatment Phase
Participants who meet pre-specified criteria may receive DNL310 or idursulfase
|
Intravenous repeating dose
Intravenous repeating dose
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Percent change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (Cohort A only)
Time Frame: 24 weeks
|
24 weeks
|
Change from baseline in the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3)(Cohort A only)
Time Frame: 96 weeks
|
96 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III)(Cohort A only)
Time Frame: 96 weeks
|
96 weeks
|
Change from baseline in distance walked in the Six-Minute Walk Test (6MWT; Cohort B only)
Time Frame: 48 weeks
|
48 weeks
|
Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations (Cohorts A and B)
Time Frame: up to 48 weeks
|
up to 48 weeks
|
Liver volume within the normal range (normal vs abnormal) as measured by magnetic resonance imaging (MRI) (Cohorts A and B)
Time Frame: 48 weeks
|
48 weeks
|
Spleen volume within the normal range (normal vs abnormal) as measured by MRI (Cohorts A and B)
Time Frame: 48 weeks
|
48 weeks
|
Improvement in Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II (Cohorts A and B)
Time Frame: 48 weeks
|
48 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Lubica Trokan, MD, MPH, Denali Therapeutics Inc.
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Genetic Diseases, Inborn
- Genetic Diseases, X-Linked
- Connective Tissue Diseases
- Carbohydrate Metabolism, Inborn Errors
- Metabolism, Inborn Errors
- Lysosomal Storage Diseases
- Mucinoses
- Mental Retardation, X-Linked
- Intellectual Disability
- Heredodegenerative Disorders, Nervous System
- Mucopolysaccharidosis II
- Mucopolysaccharidoses
Other Study ID Numbers
- DNLI-E-0007
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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