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

ConditionFacio-Scapulo-Humeral Dystrophy

Trial statusRecruiting

Trial phasePhase 1, Phase 2

Trial typeInterventional

Biological sexAll

Age16-70

SponsorArrowhead Pharmaceuticals

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

ARO-DUX4 for Injection
Drug
single or multiple doses of ARO-DUX4 by intravenous (IV) infusion
Placebo
Drug
calculated volume to match active treatment by IV infusion

Treatment groups

60 Participants

are divided into 2 treatment groups

Group A: ARO-DUX4Experimental treatment 1 intervention

Group B: PlaceboPlacebo comparator 1 intervention

Trial 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)

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