Study of ARO-DUX4 in Adult and Adolescent Patients With Facioscapulohumeral Muscular Dystrophy Type 1

Официальное название

A Phase1/2a Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-DUX4 in Adult Patients and Adolescent Patients With Facioscapulohumeral Muscular Dystrophy Type 1

Обзор

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ARO-DUX4 in participants with facioscapulohumeral muscular dystrophy Type 1 (FSHD1). In Part 1 of the study, participants will receive one dose of ARO-DUX4 or placebo. In Part 2 of the study, participants will receive 4 doses of ARO-DUX4 or placebo. Participants who complete Part 1 will have the option to re-screen and re-randomize into Part 2. All participants will undergo pre- and post-dose MRI-guided muscle biopsies (a total of 2 biopsies). Participants who complete Part 1 and enroll in Part 2 will be required to undergo an additional screening biopsy. Participants completing Part 1 or Part 2 may have the option to continue to receive drug in an open-label extension study or may be eligible to participate in later-stage clinical studies.

Вмешательства

• Препарат ARO-DUX4 for Injection
  single or multiple doses of ARO-DUX4 by intravenous (IV) infusion
• Препарат Placebo
  calculated volume to match active treatment by IV infusion

Первичные конечные точки

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Over Time Through End of Study (EOS) [Срок оценки: Part 1: Up to Day 90; Part 2: Up to Day 360]

Вторичные конечные точки (10)

• Pharmacokinetics (PK) of ARO-DUX4: Maximum Observed Plasma Concentration (Cmax) [Срок оценки: Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose]
• PK of ARO-DUX4: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24) [Срок оценки: Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose]
• PK of ARO-DUX4: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast) [Срок оценки: Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose]
• PK of ARO-DUX4: Area Under the Plasma Concentration Versus Time from Zero to Infinity (AUCinf) [Срок оценки: Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose]
• PK of ARO-DUX4: Terminal Elimination Half-Life (t1/2) [Срок оценки: Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose]
• PK of ARO-DUX4: Systemic Clearance (CL) [Срок оценки: Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose]
• PK of ARO-DUX4: Volume of Distribution (Vss) [Срок оценки: Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose]
• PK of ARO-DUX4: Recovery of Unchanged Drug in Urine Over 0-24 Hours (Amount Excreted: Ae) [Срок оценки: Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose]
• PK of ARO-DUX4: Fraction of Drug Excreted in Urine as Percent of Intravenous (IV) Dose (Fe) [Срок оценки: Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose]
• PK of ARO-DUX4: Renal Clearance (CLr) [Срок оценки: Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose]

Критерии участия

Критерии включения

• Genetically confirmed FSHD1 based on Screening evaluation or source verifiable medical record
• Clinical severity score between 3 and 8 (scale, 0 to 10)
• Must have eligible lower extremity muscle for biopsy as determined from MRI by a central reader
• A 12-lead electrocardiogram (ECG) at Screening with no abnormalities that may compromise participant's safety in the study
• Participants of childbearing potential and their partners must use highly effective contraception during the study and for at least 12 weeks following the end of study or last dose of study medication, whichever is later. Males must not donate sperm during the study from Day 1 until at least 12 weeks following the end of study or last dose of study medication, whichever is later.

Критерии исключения

• Human Immunodeficiency Virus (HIV) infection as shown by presence of anti-HIV antibody (seropositive) at Screening
• Seropositive for hepatitis B (HBV) or hepatitis C (HCV) at Screening
• Uncontrolled hypertension
• Severe cardiovascular disease
• History of thrombolic events
• Platelet count less that the lower limit of normal at Screening
• History or presence of: a hypercoagulable state, nephrotic range proteinuria, antiphospholipid antibody syndrome, myeloproliferative disease, inability to ambulate, use of hormone-based contraceptives.
• Any contraindication to muscle biopsy or MRI

Note: additional inclusion/exclusion criteria may apply per protocol

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

Четверное слепое

Основная цель

Лечение

Центры проведения

Австралия · 4 центра

• Research Site 2 — Liverpool
• Research Site 3 — Auchenflower
• Research Site 1 — Birtinya
• Research Site 4 — Melbourne

Канада · 3 центра

• Research Site 2 — Calgary
• Research Site 3 — Edmonton
• Research Site 1 — Montreal

Испания · 3 центра

• Research Site 3 — Barcelona
• Research Site 2 — Madrid
• Research Site 1 — Valencia

Германия · 2 центра

• Research Site 2 — München
• Research Site 1 — Ulm

Италия · 2 центра

• Research Site 1 — Milan
• Research Site 2 — Roma

Нидерланды · 1 центр

• Research Site 1 — Leiden

Новая Зеландия · 1 центр

• Research Site 1 — Auckland

Таиланд · 1 центр

• Research Site — Bangkok

Идентификаторы

NCT: NCT06131983 · ARODUX4-1001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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