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

Arrowhead Pharmaceuticals1 site in 1 country78 target enrollmentMarch 4, 2024

InterventionsPlacebo Subcutaneous (SC) Injection ARO-DM1 subcutaneous (SC) injection ARO-DM1 Intravenous (IV) Infusion Placebo Intravenous (IV) Infusion

Overview

Phase: Phase 1
Intervention: Placebo Subcutaneous (SC) Injection
Conditions: Myotonic Dystrophy 1
Sponsor: Arrowhead Pharmaceuticals
Enrollment: 78
Locations: 1
Primary Endpoint: Number of Participants with Treatment -Emergent Adverse Events (TEAEs) Over Time Through End of Study (EOS)
Status: Recruiting
Last Updated: 5 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

March 4, 2024

End Date

December 1, 2026

Last Updated

5 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Arrowhead Pharmaceuticals

Responsible Party

Sponsor

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)

Arms & Interventions

Placebo by SC Injection

Single or multiple doses of placebo by sc injection

Intervention: Placebo Subcutaneous (SC) Injection

ARO-DM1 Subcutaneous SC Injection

Single or multiple doses of ARO-DM1 by sc injection

Intervention: ARO-DM1 subcutaneous (SC) injection

ARO-DM1 Intravenous (IV) Infusion

Single or multiple doses of ARO-DM1 by IV infusion

Intervention: ARO-DM1 Intravenous (IV) Infusion

Placebo by IV Infusion

Single or multiple doses of placebo by IV infusion

Intervention: Placebo Intravenous (IV) Infusion

Outcomes

Primary Outcomes

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 Outcomes

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 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)
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 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 at Day 120 for Video Hand Opening Time (vHOT)((Part 2): Baseline, Day 120)
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 10-Meter Walk/Run Test (10MWT) 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 Video Hand Opening Time (vHOT) 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))