Study of ARO-DM1 in Subjects With Type 1 Myotonic Dystrophy

Официальное название

A Phase 1/2a Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-DM1 in Subjects With Type 1 Myotonic Dystrophy Who Are ≥18 to ≤ 65 Years

Обзор

This is a phase 1/2a double-blinded, placebo-controlled, dose-escalating study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple ascending doses of ARO-DM1 compared to placebo in male and female subjects with type 1 myotonic dystrophy (DM1). Participants who have provided written informed consent and met all protocol eligibility requirements will be randomized to receive single (Part 1) or multiple (Part 2) doses of ARO-DM1 or placebo.

Вмешательства

• Препарат ARO-DM1 Intravenous (IV) Infusion
  ARO-DM1 by intravenous (IV) infusion
• Препарат Placebo Intravenous (IV) Infusion
  0.9% NaCl calculated volume to match active treatment by IV infusion
• Препарат ARO-DM1 subcutaneous (SC) injection
  ARO-DM1 by subcutaneous (SC) injection(s)
• Препарат Placebo Subcutaneous (SC) Injection
  0.9% NaCl calculated volume to match active treatment by SC injection(s)

Первичные конечные точки

• Number of Participants with Treatment -Emergent Adverse Events (TEAEs) Over Time Through End of Study (EOS) [Срок оценки: Single-dose phase (Part 1): Up to Day 90(EOS); multiple-dose phase (Part 2): Up to Day 180(EOS)]

Вторичные конечные точки (11)

• Pharmacokinetics (PK) of ARO-DM1: Maximum Observed Plasma Concentration (Cmax) [Срок оценки: Single-dose phase (Part 1): Up 24 hours post-dose; multiple-dose phase (Part 2): Through 24 hours post first and second dose]
• PK of ARO-DM1: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24) [Срок оценки: Single-dose phase (Part 1): Up 24 hours post-dose; multiple-dose phase (Part 2): Through 24 hours post first and second dose]
• PK of ARO-DM1: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast) [Срок оценки: Single-dose phase (Part 1): Up 24 hours post-dose; multiple-dose phase (Part 2): Through 24 hours post first and second dose]
• PK of ARO-DM1: Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUCinf) [Срок оценки: Single-dose phase (Part 1): Up 24 hours post-dose; multiple-dose phase (Part 2): Through 24 hours post first and second dose]
• Change from Baseline at Day 120 for Video Hand Opening Time (vHOT) [Срок оценки: (Part 2): Baseline, Day 120]
• Change from Baseline Over Time for the Timed Up and Go Test (TUG) Assessment [Срок оценки: (Part 2): Baseline through EOS (up to 180 days)]
• Change from Baseline Over Time for the 10-Meter Walk/Run Test (10MWT) Assessment [Срок оценки: (Part 2): Baseline through EOS (up to 180 days)]
• Change from Baseline Over Time for the Hand-held Quantitative Dynamometry Assessment [Срок оценки: (Part 2): Baseline through EOS (up to 180 days)]
• Change from Baseline Over Time for the Video Hand Opening Time (vHOT) Assessment [Срок оценки: (Part 2): Baseline through EOS (up to 180 days)]
• Change from Baseline Over Time for the Myotonic Dystrophy Type 1 Activity and Participation Scale (DM1-Activ-C) Assessment [Срок оценки: (Part 2): Baseline through EOS (up to 180 days)]
• Change from Baseline Over Time for the Myotonic Dystrophy Health Index (MDHI) Assessment [Срок оценки: (Part 2): Baseline through EOS (up to 180 days)]

Критерии участия

Критерии включения

• Genetically confirmed diagnosis of DM1
• Clinician-assessed signs of DM1 including clinically apparent myotonia
• Onset of DM1 symptoms occurred after the age of 12 years
• Walk for at least 10 meters independently at Screening
• Subjects of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 90 days following the end of study or last dose of study drug, whichever is later. Subjects must not donate sperm or eggs during the study and for at least 90 days following the end of study or last dose of study drug whichever is later.

Критерии исключения

• Inadequately controlled diabetes
• Confirmed diagnosis of congenital DM1
• Uncontrolled hypertension
• History of tibialis anterior (TA) biopsy within 3 months of Day 1 or planning to undergo TA biopsies during the study period
• Clinically significant cardiac, liver or renal disease
• HIV infection (seropositive) at Screening
• Seropositive for hepatitis B (HBV) or hepatitis C (HCV) at screening
• Untreated or poorly controlled epilepsy
• Treatment with anti-myotonia medication within a period of 5 half-lives of the medication prior to Screening.
• Abnormal coagulation parameters at Screening including platelet count, international normalized ratio (INR), prothrombin time, and activated partial thromboplastin time (APTT)

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 — Liverpool
• Research Site — Birtinya
• Research Site — Herston
• Research Site — Melbourne

Тайвань · 3 центра

• Research Site — Taichung
• Research Site — Taipei
• Research Site — Taipei

Таиланд · 3 центра

• Research Site — Bangkok
• Research Site — Hat Yai
• Research Site — Lampang

Новая Зеландия · 1 центр

• Research Site — Christchurch

Идентификаторы

NCT: NCT06138743 · ARODM1-1001 · 2024-513579-42

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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