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

Myotonic Dystrophy 1 Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06138743
• Other study ID #: ARODM1-1001
• Status: Recruiting
• Phase: Phase 1
• Start date: March 4, 2024
• Est. completion date: October 2026

Study information

• Verified date: March 2024
• Source: Arrowhead Pharmaceuticals
• Contact: Medical Monitor
• Phone: 626-304-3400
• Email: ARO-DM1[@]arrowheadpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: October 2026
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Genetically confirmed diagnosis of DM1
• Clinician-assessed signed 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. Note: Additional inclusion/exclusion criteria may apply per protocol

Related Conditions & MeSH terms

• Myotonic Dystrophy
• Myotonic Dystrophy 1

Intervention

Drug:
• ARO-DM1 for Injection
single or multiple doses of ARO-DM1 by intravenous (IV) infusion
• Placebo
calculated volume to match active treatment by IV infusion

Locations

Country	Name	City	State
Australia	Research Site	Herston	Queensland
New Zealand	Research Site	Christchurch

Sponsors (1)

Lead Sponsor	Collaborator
Arrowhead Pharmaceuticals

Countries where clinical trial is conducted

Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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; Multiple dose phase (Part 2): Up to Day 180 or Day 360
Secondary	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
Secondary	PK of ARO-DM1: Time to Maximum Observed Plasma Concentration (Tmax)		Single dose phase (Part 1): Up 24 hours post-dose; Multiple dose phase (Part 2): Through 24 hours post first and second dose
Secondary	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
Secondary	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
Secondary	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
Secondary	PK of ARO-DM1: Elimination half-life (t1/2)		Single dose phase (Part 1): Up 24 hours post-dose; Multiple dose phase (Part 2): Through 24 hours post first and second dose
Secondary	PK of ARO-DM1: Apparent Systemic Clearance (CL/F)		Single dose phase (Part 1): Up 24 hours post-dose; Multiple dose phase (Part 2): Through 24 hours post first and second dose
Secondary	PK of ARO-DM1:m Apparent Terminal-phase Volume of Distribution (Vz/F)		Single dose phase (Part 1): Up 24 hours post-dose; Multiple dose phase (Part 2): Through 24 hours post first and second dose