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

Phase 1

Recruiting

• Conditions: Myotonic Dystrophy 1
• Interventions: Drug: ARO-DM1 for Injection; Drug: Placebo

• Registration Number: NCT06138743
• Lead Sponsor: Arrowhead Pharmaceuticals

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-11-14
• Study First Submitted QC: 2023-11-14
• Study First Posted: 2023-11-18
• Study Start: 2024-03-04
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-07
• Last Update Posted: 2025-08-12
• Primary Completion: 2026-09
• Study Completion: 2026-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ARO-DM1	ARO-DM1 for Injection	ARO-DM1 for Injection
Placebo	Placebo	(0.9% NaCl)

Primary Outcome Measures

Name	Time	Method
Number of Participants with Treatment -Emergent Adverse Events (TEAEs) Over Time Through End of Study (EOS)	Single dose phase (Part 1): Up to Day 90(EOS); Multiple dose phase (Part 2): Up to Day 180(EOS)
Change from Baseline in Skeletal Muscle Dystrophia Myotonica-Protein Kinase (DMPK) Mediated Changes in the Composite Myotonic Dystrophy Type 1 Splicing Indices	(Part 2): Baseline, Up to Day 120

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Research Site; 🇹🇭 Lampang, Thailand