A Phase1/2a Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-DUX4 in Adult Patients and Adolescent Patients With Facioscapulohumeral Muscular Dystrophy Type 1

Arrowhead Pharmaceuticals17 sites in 8 countries60 target enrollmentFebruary 22, 2024

InterventionsARO-DUX4 for Injection Placebo

Overview

Phase: Phase 1
Intervention: ARO-DUX4 for Injection
Conditions: Not specified
Sponsor: Arrowhead Pharmaceuticals
Enrollment: 60
Locations: 17
Primary Endpoint: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Over Time Through End of Study (EOS)
Status: Recruiting
Last Updated: 2 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ARO-DUX4 in participants with facioscapulohumeral muscular dystrophy Type 1 (FSHD1). In Part 1 of the study, participants will receive one dose of ARO-DUX4 or placebo. In Part 2 of the study, participants will receive 4 doses of ARO-DUX4 or placebo. Participants who complete Part 1 will have the option to re-screen and re-randomize into Part 2. All participants will undergo pre- and post-dose MRI-guided muscle biopsies (a total of 2 biopsies). Participants who complete Part 1 and enroll in Part 2 will be required to undergo an additional screening biopsy. Participants completing Part 1 or Part 2 may have the option to continue to receive drug in an open-label extension study or may be eligible to participate in later-stage clinical studies.

Registry

euclinicaltrials.eu

Start Date

February 22, 2024

End Date

December 1, 2026

Last Updated

2 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Arrowhead Pharmaceuticals

Responsible Party

Sponsor

Principal Investigator

Dillon Chen

Scientific

Arrowhead Pharmaceuticals Inc.

Eligibility Criteria

Inclusion Criteria

•Genetically confirmed FSHD1 based on Screening evaluation or source verifiable medical record
•Clinical severity score between 3 and 8 (scale, 0 to 10)
•Must have eligible lower extremity muscle for biopsy as determined from MRI by a central reader
•A 12-lead electrocardiogram (ECG) at Screening with no abnormalities that may compromise participant's safety in the study
•Participants of childbearing potential and their partners must use highly effective contraception during the study and for at least 12 weeks following the end of study or last dose of study medication, whichever is later. Males must not donate sperm during the study from Day 1 until at least 12 weeks following the end of study or last dose of study medication, whichever is later.

Exclusion Criteria

•Human Immunodeficiency Virus (HIV) infection as shown by presence of anti-HIV antibody (seropositive) at Screening
•Seropositive for hepatitis B (HBV) or hepatitis C (HCV) at Screening
•Uncontrolled hypertension
•Severe cardiovascular disease
•History of thrombolic events
•Platelet count less that the lower limit of normal at Screening
•History or presence of: a hypercoagulable state, nephrotic range proteinuria, antiphospholipid antibody syndrome, myeloproliferative disease, inability to ambulate, use of hormone-based contraceptives.
•Any contraindication to muscle biopsy or MRI
•Note: additional inclusion/exclusion criteria may apply per protocol

Arms & Interventions

ARO-DUX4

ARO-DUX4 for Injection

Intervention: ARO-DUX4 for Injection

Placebo

(0.9%NaCl)

Intervention: Placebo

Outcomes

Primary Outcomes

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Over Time Through End of Study (EOS)

Time Frame: Part 1: Up to Day 90; Part 2: Up to Day 360

Secondary Outcomes

Pharmacokinetics (PK) of ARO-DUX4: Maximum Observed Plasma Concentration (Cmax)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
PK of ARO-DUX4: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
PK of ARO-DUX4: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
PK of ARO-DUX4: Area Under the Plasma Concentration Versus Time from Zero to Infinity (AUCinf)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
PK of ARO-DUX4: Terminal Elimination Half-Life (t1/2)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
PK of ARO-DUX4: Systemic Clearance (CL)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
PK of ARO-DUX4: Volume of Distribution (Vss)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
PK of ARO-DUX4: Recovery of Unchanged Drug in Urine Over 0-24 Hours (Amount Excreted: Ae)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
PK of ARO-DUX4: Fraction of Drug Excreted in Urine as Percent of Intravenous (IV) Dose (Fe)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
PK of ARO-DUX4: Renal Clearance (CLr)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)