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

Official title

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

Overview

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.

Interventions

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

Primary outcome measures

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

Secondary outcome measures (11)

• Pharmacokinetics (PK) of ARO-DM1: Maximum Observed Plasma Concentration (Cmax) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: (Part 2): Baseline, Day 120]
• Change from Baseline Over Time for the Timed Up and Go Test (TUG) Assessment [Time frame: (Part 2): Baseline through EOS (up to 180 days)]
• Change from Baseline Over Time for the 10-Meter Walk/Run Test (10MWT) Assessment [Time frame: (Part 2): Baseline through EOS (up to 180 days)]
• Change from Baseline Over Time for the Hand-held Quantitative Dynamometry Assessment [Time frame: (Part 2): Baseline through EOS (up to 180 days)]
• Change from Baseline Over Time for the Video Hand Opening Time (vHOT) Assessment [Time frame: (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 [Time frame: (Part 2): Baseline through EOS (up to 180 days)]
• Change from Baseline Over Time for the Myotonic Dystrophy Health Index (MDHI) Assessment [Time frame: (Part 2): Baseline through EOS (up to 180 days)]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Australia · 4 centers

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

Taiwan · 3 centers

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

Thailand · 3 centers

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

New Zealand · 1 center

• Research Site — Christchurch

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗