An Extension Study of the Long-Term Safety, Tolerability, and Efficacy of Tividenofusp Alfa (DNL310) in Participants With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007

Официальное название

An Open-Label Extension to Investigate the Long-Term Safety, Tolerability, and Efficacy of DNL310 in Patients With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007

Обзор

This is a multiregional open-label extension (OLE) to assess the safety, tolerability, and efficacy of long-term treatment with tividenofusp alfa (DNL310), an investigational central nervous system (CNS)-penetrant intravenous (IV) enzyme replacement therapy (ERT) for Hunter syndrome (MPS II). Participants who complete at least through the Week 49 visit in Study DNLI-E-0002 and do not discontinue study intervention early and participants who complete Study DNLI-E-0007 will be enrolled in this OLE. All participants will receive DNL310 for up to 5 years from the time of entry in this OLE. Participants, site staff, and the Sponsor will remain blinded to the original treatment assignment for participants entering this OLE from Study DNLI-E-0007.

Вмешательства

• Препарат tividenofusp alfa
  Intravenous repeating dose

Первичные конечные точки

• Incidence and intensity of treatment-emergent adverse events (TEAEs) [Срок оценки: 5 years]
• Clinically significant changes in urine total glycosaminoglycan (GAG) concentrations throughout the treatment period [Срок оценки: 5 years]
• Incidence and intensity of infusion-related reactions (IRRs) [Срок оценки: 5 years]

Вторичные конечные точки (8)

• Percentage change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration [Срок оценки: 5 years]
• Change from baseline in the Vineland-3 Adaptive Behavior Scale [Срок оценки: 5 years]
• Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) cognitive raw score [Срок оценки: 5 years]
• Change from baseline in distance walked (meters) in the Six-Minute Walk Test (6MWT) [Срок оценки: 5 years]
• Percent change from baseline in the sum of urine HS and dermatan sulfate (DS) concentrations [Срок оценки: 5 years]
• Liver volume within the normal range (normal vs abnormal) as measured by MRI [Срок оценки: 5 years]
• Spleen volume within the normal range (normal vs abnormal) as measured by MRI [Срок оценки: 5 years]
• Improvement in the Parent/Caregiver Global Impression of Change (CaGI-C) Overall MPS II [Срок оценки: 5 years]

Критерии участия

Критерии включения

• For participants from Study DNLI-E-0002 only: Completed at least through the Week 49 visit in Study DNLI-E-0002 and did not discontinue study intervention early
• For participants from Study DNLI-E-0007 only: Completed the treatment period of 96 weeks in Cohort A for nMPS II participants and 48 weeks in Cohort B for nnMPS II participants

Критерии исключения

• Unstable or poorly controlled medical condition(s) or significant medical or psychological comorbidity or comorbidities that, in the opinion of the investigator, would interfere with safe participation in the trial or interpretation of study assessments

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

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
• Huntsman Cancer Hospital — Salt Lake City

Великобритания · 4 центра

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

Канада · 3 центра

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

Бельгия · 2 центра

• Universitair Ziekenhuis Antwerpen — Edegem
• UZ Brussel — Jette

Германия · 2 центра

• Universitätsklinikum Hamburg-Eppendorf — Hamburg
• SpinCS GmbH — Höchheim

Италия · 2 центра

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

Turkey (Türkiye) · 2 центра

• University Medical Faculty Balcali Hospital — Adana
• Gazi Universitesi Tip Fakultes — Ankara

Аргентина · 1 центр

• Sanatorio Mater Dei — Buenos Aires

Чехия · 1 центр

• Vseobecna Fakultni Nemocnice V Praze — Prague

Франция · 1 центр

• Hopital Jeanne De Flandre - Metabolic Diseases Unit — Lille

Нидерланды · 1 центр

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

Испания · 1 центр

• Hospit U. Vall d'Hebron - PPDS — Barcelona

Швеция · 1 центр

• Drottning Silvias Barn Och Ungdomssjukhus — Gothenburg

Идентификаторы

NCT: NCT06075537 · DNLI-E-0008 · 2023-503837-23

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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