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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
60
single or multiple doses of ARO-DUX4 by intravenous (IV) infusion
calculated volume to match active treatment by IV infusion
Research Site 2
Liverpool, New South Wales, Australia
RECRUITINGResearch Site 3
Auchenflower, Queensland, Australia
RECRUITINGResearch Site 1
Birtinya, Queensland, Australia
RECRUITINGResearch Site 4
Melbourne, Victoria, Australia
RECRUITINGResearch Site 2
Calgary, Alberta, Canada
NOT_YET_RECRUITINGResearch Site 3
Edmonton, Alberta, Canada
RECRUITINGResearch Site 1
Montreal, Quebec, Canada
RECRUITINGResearch Site 2
München, Germany
RECRUITINGResearch Site 1
Ulm, Germany
RECRUITINGResearch Site 1
Milan, Italy
RECRUITING...and 7 more locations
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
Pharmacokinetics (PK) of ARO-DUX4: Maximum Observed Plasma Concentration (Cmax)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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
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