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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06131983




Registration number
NCT06131983
Ethics application status
Date submitted
8/11/2023
Date registered
15/11/2023
Date last updated
24/10/2024

Titles & IDs
Public title
Study of ARO-DUX4 in Adult Patients With Facioscapulohumeral Muscular Dystrophy Type 1
Scientific 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
Secondary ID [1] 0 0
ARODUX4-1001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Facio-Scapulo-Humeral Dystrophy 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Neurological 0 0 0 0
Other neurological disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ARO-DUX4 for Injection
Treatment: Drugs - Placebo

Experimental: ARO-DUX4 - ARO-DUX4 for Injection

Placebo comparator: Placebo - (0.9%NaCl)


Treatment: Drugs: ARO-DUX4 for Injection
single or multiple doses of ARO-DUX4 by intravenous (IV) infusion

Treatment: Drugs: Placebo
calculated volume to match active treatment by IV infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Over Time Through End of Study (EOS)
Timepoint [1] 0 0
Part 1: Up to Day 90; Part 2: Up to Day 360
Secondary outcome [1] 0 0
Pharmacokinetics (PK) of ARO-DUX4: Maximum Observed Plasma Concentration (Cmax)
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
PK of ARO-DUX4: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
PK of ARO-DUX4: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast)
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
PK of ARO-DUX4: Area Under the Plasma Concentration Versus Time from Zero to Infinity (AUCinf)
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
PK of ARO-DUX4: Terminal Elimination Half-Life (t1/2)
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
PK of ARO-DUX4: Systemic Clearance (CL)
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
PK of ARO-DUX4: Volume of Distribution (Vss)
Timepoint [7] 0 0
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
Secondary outcome [8] 0 0
PK of ARO-DUX4: Recovery of Unchanged Drug in Urine Over 0-24 Hours (Amount Excreted: Ae)
Timepoint [8] 0 0
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
Secondary outcome [9] 0 0
PK of ARO-DUX4: Fraction of Drug Excreted in Urine as Percent of Intravenous (IV) Dose (Fe)
Timepoint [9] 0 0
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
Secondary outcome [10] 0 0
PK of ARO-DUX4: Renal Clearance (CLr)
Timepoint [10] 0 0
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

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/02/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/09/2025
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Research Site - Liverpool
Recruitment hospital [2] 0 0
Research Site - Auchenflower
Recruitment hospital [3] 0 0
Research Site - Birtinya
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
4066 - Auchenflower
Recruitment postcode(s) [3] 0 0
4575 - Birtinya
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
Thailand
State/province [2] 0 0
Bangkok

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Arrowhead Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT06131983
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Medical Monitor
Address 0 0
Country 0 0
Phone 0 0
626-304-3400
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06131983