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

• ClinicalTrials.gov Identifier: NCT06138743
• Recruitment Status: Recruiting
• First Posted: November 18, 2023
• Last Update Posted: April 19, 2024
• Sponsor: Arrowhead Pharmaceuticals
• Information provided by (Responsible Party): Arrowhead Pharmaceuticals

Tracking Information

• First Submitted Date: November 14, 2023
• First Posted Date: November 18, 2023
• Last Update Posted Date: April 19, 2024
• Actual Study Start Date: March 4, 2024
• Estimated Primary Completion Date: October 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 14, 2023): 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; Multiple dose phase (Part 2): Up to Day 180 or Day 360 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 14, 2023)

• 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: Time to Maximum Observed Plasma Concentration (Tmax) [ 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 ]
• PK of ARO-DM1: Elimination half-life (t1/2) [ 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: Apparent Systemic Clearance (CL/F) [ 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:m Apparent Terminal-phase Volume of Distribution (Vz/F) [ 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 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Myotonic Dystrophy 1

Intervention

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

Study Arms

• Experimental: ARO-DM1
  ARO-DM1 for Injection
  Intervention: Drug: ARO-DM1 for Injection
• Placebo Comparator: Placebo
  (0.9% NaCl)
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 14, 2023): 48
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2026
• Estimated Primary Completion Date: October 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Medical Monitor; 626-304-3400; ARO-DM1@arrowheadpharma.com

• Listed Location Countries: Australia, New Zealand

Administrative Information

• NCT Number: NCT06138743
• Other Study ID Numbers: ARODM1-1001
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Arrowhead Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Arrowhead Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Arrowhead Pharmaceuticals
• Verification Date: March 2024