Clinical trial NCT06131983: Study of ARO-DUX4 in Adult Patients With Facioscapulohumeral Muscular Dystrophy Type 1
Official title: A Phase1/2a Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-DUX4 in Adult Patients With Facioscapulohumeral Muscular Dystrophy Type 1
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Facio-Scapulo-Humeral Dystrophy
Lead sponsor: Arrowhead Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-11-15
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Over Time Through End of Study (EOS)
timeFrame: Part 1: Up to Day 90; Part 2: Up to Day 360
Secondary outcomes:
measure: Pharmacokinetics (PK) of ARO-DUX4: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 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
measure: PK of ARO-DUX4: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)
timeFrame: 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
measure: PK of ARO-DUX4: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast)
timeFrame: 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
measure: PK of ARO-DUX4: Area Under the Plasma Concentration Versus Time from Zero to Infinity (AUCinf)
timeFrame: 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
measure: PK of ARO-DUX4: Terminal Elimination Half-Life (t1/2)
timeFrame: 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
measure: PK of ARO-DUX4: Systemic Clearance (CL)
timeFrame: 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
measure: PK of ARO-DUX4: Volume of Distribution (Vss)
timeFrame: 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
measure: PK of ARO-DUX4: Recovery of Unchanged Drug in Urine Over 0-24 Hours (Amount Excreted: Ae)
timeFrame: 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
measure: PK of ARO-DUX4: Fraction of Drug Excreted in Urine as Percent of Intravenous (IV) Dose (Fe)
timeFrame: 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
measure: PK of ARO-DUX4: Renal Clearance (CLr)
timeFrame: 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
Other outcomes:
Locations:
city: Liverpool
country: Australia
facility: Research Site
state: New South Wales
city: Auchenflower
country: Australia
facility: Research Site
state: Queensland
city: Birtinya
country: Australia
facility: Research Site
state: Queensland
city: Auckland
country: New Zealand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
Study officials:
References: