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)

Официальное название

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

Обзор

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.

Вмешательства

• Препарат tividenofusp alfa
  Intravenous repeating dose
• Препарат idursulfase
  Intravenous repeating dose

Первичные конечные точки

• Percent change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (Cohort A) [Срок оценки: 24 weeks]
• Change from baseline in the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3)(Cohort A) [Срок оценки: 96 weeks]

Вторичные конечные точки (8)

• Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III)(Cohort A only) [Срок оценки: 96 weeks]
• Change from baseline in the Vineland-3 Adaptive Behavior Composite (ABC; Cohort A only) [Срок оценки: 96 weeks]
• Change from baseline in serum neurofilament light chain (NfL) (Cohort A only) [Срок оценки: 96 weeks]
• Change from baseline in distance walked in the Six-Minute Walk Test (6MWT; Cohort B only) [Срок оценки: 48 weeks]
• Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations (Cohorts A and B) [Срок оценки: up to 48 weeks]
• Liver volume within the normal range (normal vs abnormal) as measured by magnetic resonance imaging (MRI) (Cohorts A and B) [Срок оценки: 48 weeks]
• Spleen volume within the normal range (normal vs abnormal) as measured by MRI (Cohorts A and B) [Срок оценки: 48 weeks]
• Improvement in Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II (Cohorts A and B) [Срок оценки: 48 weeks]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 8 центров

• UCSF Benioff Children's Hospital Oakland — Oakland
• Ann and Robert H Lurie Children's Hospital of Chicago — Chicago
• Hackensack University Medical Center — Hackensack
• UNC Children's Research Institute — Chapel Hill
• Cincinnati Children's Hospital Medical Center — Cincinnati
• Children's Hospital of Philadelphia — Philadelphia
• The University of Texas Medical School at Houston — Houston
• University of Utah, PPDS — Salt Lake City

Великобритания · 4 центра

• Great Ormond Street Hospital for Children — London
• Birmingham Women's and Children's NHS Foundation Trust — Birmingham
• Royal Free Hospital — London
• Salford Royal Hospital — Salford

Канада · 3 центра

• University of Alberta - Faculty of Medicine & Dentistry — Edmonton
• Hospital for Sick Children — Toronto
• McGill University Health Center — Montreal

Бельгия · 2 центра

• UZ Antwerpen — Antwerp
• Universitair Ziekenhuis Brussel — Jette

Бразилия · 2 центра

• Hospital de Clínicas de Porto Alegre (HCPA) - PPDS — Porto Alegre
• Instituto Fernandes Figueira — Rio de Janeiro

Германия · 2 центра

• SphinCS — Höchheim
• Medizinische Universität Lausitz - Carl Thiem — Cottbus

Испания · 2 центра

• Hospital Universitario Vall d'Hebron — Barcelona
• Hospital Infantil Universitario Niño Jesus — Madrid

Turkey (Türkiye) · 2 центра

• Cukurova University Medical Faculty Balcali Hospital — Adana
• Gazi Universitesi Tip Fakultesi — Çankaya

Аргентина · 1 центр

• Sanatorio Mater Dei — Buenos Aires

Австралия · 1 центр

• Women's and Children's Hospital — North Adelaide

Чехия · 1 центр

• Vseobecna Fakultni Nemocnice V Praze — Prague

Франция · 1 центр

• Hôpital Jeanne de Flandre — Lille

Италия · 1 центр

• Azienda Sanitaria Universitaria Friuli Centrale - PO Universitario Santa Maria della Miser — Udine

Нидерланды · 1 центр

• Erasmus Medical Center - Sophia Children's Hospital — Rotterdam

Швеция · 1 центр

• Drottning Silvias Barn Och Ungdomssjukhus — Gothenburg

Идентификаторы

NCT: NCT05371613 · DNLI-E-0007 · 2024-510990-21-00 · 2021-005200-35

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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