Study of ARO-DUX4 in Adult and Adolescent Patients With Facioscapulohumeral Muscular Dystrophy Type 1

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

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.

Study Overview

• Status: Recruiting
• Conditions: Facio-Scapulo-Humeral Dystrophy
• Intervention / Treatment: Drug: ARO-DUX4 for Injection; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Medical Monitor; Phone Number: 626-304-3400; Email: ARO_DUX4@arrowheadpharma.com

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Recruiting
      • Research Site 2
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Recruiting
      • Research Site 3
    • Birtinya, Queensland, Australia, 4575
      • Recruiting
      • Research Site 1
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Research Site 4
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N4Z6
      • Not yet recruiting
      • Research Site 2
    • Edmonton, Alberta, Canada, T6G2G4
      • Recruiting
      • Research Site 3
  • Quebec
    • Montreal, Quebec, Canada, H3A2B4
      • Recruiting
      • Research Site 1
• Germany
  • München, Germany, 80336
    • Recruiting
    • Research Site 2
  • Ulm, Germany, 89081
    • Recruiting
    • Research Site 1
• Italy
  • Milan, Italy, 20162
    • Recruiting
    • Research Site 1
  • Roma, Italy, 00168
    • Recruiting
    • Research Site 2
• Netherlands
  • Leiden, Netherlands, 2333
    • Recruiting
    • Research Site 1
• New Zealand
  • Auckland, New Zealand, 1010
    • Recruiting
    • Research Site 1
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Research Site 3
  • Madrid, Spain, 28034
    • Recruiting
    • Research Site 2
  • Valencia, Spain, 46026
    • Recruiting
    • Research Site 1
• Thailand
  • Bangkok, Thailand, 10700
    • Withdrawn
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARO-DUX4; ARO-DUX4 for Injection	Drug: ARO-DUX4 for Injection; single or multiple doses of ARO-DUX4 by intravenous (IV) infusion
Placebo Comparator: Placebo; (0.9%NaCl)	Drug: Placebo; calculated volume to match active treatment by IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Over Time Through End of Study (EOS)	Part 1: Up to Day 90; Part 2: Up to Day 360

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 8, 2023
• First Submitted That Met QC Criteria: November 13, 2023
• First Posted (Actual): November 15, 2023

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 4, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Muscular Disorders, Atrophic; Muscular Dystrophies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Muscular Dystrophy, Facioscapulohumeral; Therapeutics; Drug Administration Routes; Drug Therapy; Injections
• Other Study ID Numbers: ARODUX4-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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