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)

Mucopolysaccharidosis II Clinical Trial

— COMPASS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05371613
• Other study ID #: DNLI-E-0007
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: July 21, 2022
• Est. completion date: December 2025

Study information

• Verified date: June 2024
• Source: Denali Therapeutics Inc.
• Contact: Clinical Trials at Denali Therapeutics
• Email: clinical-trials[@]dnli.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 16 Years

Eligibility

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

Related Conditions & MeSH terms

• Mucopolysaccharidoses
• Mucopolysaccharidosis II

Intervention

Drug:
• tividenofusp alfa
Intravenous repeating dose
• idursulfase
Intravenous repeating dose

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aires	Buenos Aires
Argentina	Sanatorio Mater Dei	Buenos Aires
Belgium	UZ Antwerpen	Antwerpen
Belgium	Universitair Ziekenhuis Brussel	Jette	Brussels
Brazil	Hospital de Clínicas de Porto Alegre (HCPA) - PPDS	Porto Alegre
Brazil	Instituto Fernandes Figueira	Rio De Janeiro
Canada	University of Alberta - Faculty of Medicine & Dentistry	Edmonton	Alberta
Canada	McGill University Health Center	Montreal	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
Colombia	Fundación Cardioinfantil Instituto Cardiológico	Bogotá
Czechia	Vseobecna Fakultni Nemocnice V Praze	Praha
France	Hôpital Jeanne de Flandre	Lille
France	Hopitaux de La Timone	Marseille
France	CHU Toulouse	Toulouse
Germany	UKGM - Universitätsklinikum Gießen und Marburg GmbH - Standort Gießen	Giessen
Germany	Universitätsklinikum Hamburg Eppendorf	Hamburg
Germany	SphinCS	Hochheim
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli
Italy	Azienda Sanitaria Universitaria Friuli Centrale - PO Universitario Santa Maria della Misericordia	Udine
Netherlands	Erasmus Medical Center - Sophia Children's Hospital	Rotterdam
Spain	Hospital Clínico Universitario de Santiago	A Coruña
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Infantil Universitario Niño Jesus	Madrid
Sweden	Drottning Silvias Barn Och Ungdomssjukhus	Göteborg
Turkey	Cukurova University Medical Faculty Balcali Hospital	Adana
Turkey	Gazi Universitesi Tip Fakultesi	Çankaya
United Kingdom	Birmingham Women's and Children's NHS Foundation Trust	Birmingham
United Kingdom	Great Ormond Street Hospital for Children	London
United States	Emory University	Atlanta	Georgia
United States	UNC Children's Research Institute	Chapel Hill	North Carolina
United States	Ann and Robert H Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	The University of Texas Medical School at Houston	Houston	Texas
United States	UCSF Benioff Children's Hospital Oakland	Oakland	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of Utah, PPDS	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Denali Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Colombia,  Czechia,  France,  Germany,  Italy,  Netherlands,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (Cohort A only)		24 weeks
Primary	Change from baseline in the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3)(Cohort A only)		96 weeks
Secondary	Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III)(Cohort A only)		96 weeks
Secondary	Change from baseline in distance walked in the Six-Minute Walk Test (6MWT; Cohort B only)		48 weeks
Secondary	Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations (Cohorts A and B)		up to 48 weeks
Secondary	Liver volume within the normal range (normal vs abnormal) as measured by magnetic resonance imaging (MRI) (Cohorts A and B)		48 weeks
Secondary	Spleen volume within the normal range (normal vs abnormal) as measured by MRI (Cohorts A and B)		48 weeks
Secondary	Improvement in Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II (Cohorts A and B)		48 weeks

External Links

•   Engage Hunter Website