Clinical trial NCT06138743: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Myotonic Dystrophy 1
Lead sponsor: Arrowhead Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-11-18
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 thromboembolic events
* 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)
* History or presence of any of the following: hypercoagulable state, nephrotic range proteinuria, antiphospholipid antibody syndrome or myeloproliferative diseases, inability to ambulate, use of hormone-based contraceptives and peri/post- menopausal hormone replacement therapy ≤ 16 weeks prior to Day 1

Note: Additional inclusion/exclusion criteria may apply per protocol

Primary outcomes:
measure: Number of Participants with Treatment -Emergent Adverse Events (TEAEs) Over Time Through End of Study (EOS)
timeFrame: Single dose phase (Part 1): Up to Day 90(EOS); Multiple dose phase (Part 2): Up to Day 180(EOS)
Secondary outcomes:
measure: Pharmacokinetics (PK) of ARO-DM1: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Single dose phase (Part 1): Up 24 hours post-dose; Multiple dose phase (Part 2): Through 24 hours post first and second dose
measure: PK of ARO-DM1: Time to Maximum Observed Plasma Concentration (Tmax)
timeFrame: Single dose phase (Part 1): Up 24 hours post-dose; Multiple dose phase (Part 2): Through 24 hours post first and second dose
measure: PK of ARO-DM1: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)
timeFrame: Single dose phase (Part 1): Up 24 hours post-dose; Multiple dose phase (Part 2): Through 24 hours post first and second dose
measure: PK of ARO-DM1: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast)
timeFrame: Single dose phase (Part 1): Up 24 hours post-dose; Multiple dose phase (Part 2): Through 24 hours post first and second dose
measure: PK of ARO-DM1: Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUCinf)
timeFrame: Single dose phase (Part 1): Up 24 hours post-dose; Multiple dose phase (Part 2): Through 24 hours post first and second dose
measure: PK of ARO-DM1: Elimination half-life (t1/2)
timeFrame: Single dose phase (Part 1): Up 24 hours post-dose; Multiple dose phase (Part 2): Through 24 hours post first and second dose
measure: PK of ARO-DM1: Apparent Systemic Clearance (CL/F)
timeFrame: Single dose phase (Part 1): Up 24 hours post-dose; Multiple dose phase (Part 2): Through 24 hours post first and second dose
measure: PK of ARO-DM1:m Apparent Terminal-phase Volume of Distribution (Vz/F)
timeFrame: Single dose phase (Part 1): Up 24 hours post-dose; Multiple dose phase (Part 2): Through 24 hours post first and second dose
Other outcomes:
Locations:
city: Birtinya
country: Australia
facility: Research Site
state: Queensland
city: Herston
country: Australia
facility: Research Site
state: Queensland
city: Melbourne
country: Australia
facility: Research Site
state: Victoria
city: Christchurch
country: New Zealand
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
state: Songkhla
city: Bangkok
country: Thailand
facility: Research Site
Study officials:
References: