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.
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
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