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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sarepta Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

19 Feb 2025 → ongoing

Decision date (initial)

2024-08-13

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Arrowhead Pharmaceuticals, Inc.

External identifiers

EU CT number

2023-509748-89-00

ClinicalTrials.gov

NCT06131983

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacokinetic, Pharmacodynamic, Safety

To evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of ARO-DUX4 using escalating single and multiple doses in subjects with facioscapulohumeral muscular dystrophy Type 1 (FSHD1).

Conditions and MedDRA coding

Facioscapulohumeral muscular dystrophy (FSHD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Genetically confirmed FSHD1 (based on Screening evaluation or source verifiable medical record). If available, the number of repeats (1 to 10) via assessment of the size of the D4Z4 array on chromosome 4 should be provided. Confirmation must be obtained prior to the baseline muscle biopsy.
2. Clinical severity score (CSS) between 3 and 8 (scale, 0 to 10)
3. Must have an eligible lower extremity muscle for biopsy as determined from MRI by a central reader, with MFF ≥10% and less than approximately 40%.
4. Males or nonpregnant, nonlactating females ≥18 years of age who do not plan to become pregnant during the study, with an upper age limit of ≤70 years.
5. Able and willing to provide written informed consent prior to the performance of any study specific procedures.
6. Subjects with a body mass index (BMI) between 18.0 and 35.0 kg/m2, inclusive. A subject with FSHD1 and a BMI outside this range may be allowed into the study at the discretion of the PI.
7. A 12-lead ECG at Screening with no abnormalities that may compromise the subject’s safety in this study per PI discretion.
8. Subjects of childbearing potential and their partners must agree to use highly effective contraception during the study and for at least 9 months following the end of the study or last dose of IP, whichever is later. Males must not donate sperm during the study from Day 1 until at least 9 months following the end of the study or last dose of IP, whichever is later.
9. Must be willing and able to comply with all study assessments and adhere to the protocol schedule.

Exclusion criteria 22

1. Is unable to comply with the study requirements, including the number of required visits to the clinical site.
2. HIV infection, as shown by the presence of anti-HIV antibody (seropositive) at Screening.
3. Seropositive for hepatitis B (positive HBsAg at Screening) or hepatitis C (HCV) at Screening, (positive for anti-HCV antibody must be confirmed with positive HCV-RNA test for exclusion).
4. Uncontrolled hypertension (blood pressure >160/100 mmHg at Screening, confirmed by repeat).
5. A history of torsade de pointes, ventricular rhythm disturbances (eg, ventricular tachycardia or fibrillation), heart block (excluding first-degree block, being PR interval prolongation only), congenital long QT syndrome, new ST segment elevation or depression, or new Q wave on ECG. Subjects with a history of atrial arrhythmias should be discussed with the Medical Monitor.
6. Symptomatic heart failure (per New York Heart Association [NYHA] guidelines), unstable angina, myocardial infarction, peripheral vascular disease, atherosclerotic cardiovascular disease, severe cardiovascular disease (ejection fraction <20%, transient ischemic attack, or cerebrovascular accident within 6 months prior to Day 1) or history of active smoking (tobacco).
7. History of malignancy within the last 2 years except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer. Subjects with other curatively treated malignancies who have no evidence of metastatic disease and >2-year disease-free interval may be entered following approval by the Medical Monitor.
8. History of major surgery within 3 months of Screening.
9. Regular use of alcohol within 1 month prior to the Screening visit (ie, more than 14 units of alcohol per week [1 unit=150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol]).
10. Use of an investigational agent or device within 30 days (or longer as per local regulations) prior to dosing or current participation in an investigational study.
11. Blood donation (500 mL) within 7 days prior to study treatment administration. Donation or loss of whole blood (excluding the volume of blood that will be drawn during the Screening procedures of this study) prior to administration of the study treatment as follows: 50 mL to 499 mL of whole blood within 30 days, or more than 499 mL of whole blood within 56 days prior to study treatment administration.
12. Any concomitant medical or psychiatric condition or social situation that would make it difficult to comply with protocol requirements or put the subject at additional safety risk.
13. Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 calculated by using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation (CKD-EPI).
14. Current concomitant use of theophylline (including duration of study).
15. History of thromboembolic events including deep vein thrombosis, thrombotic stroke, pulmonary embolism, or atrial thrombi.
16. Thrombocytopenia (platelet count less than the lower limit of normal) at Screening.
17. History or presence of any of the following based on source verifiable medical record and physical exam or reported medical history when applicable: • a hypercoagulable state including factor V Leiden mutation, increased factor VIII, increased proteins C and S, and antithrombin deficiency • nephrotic range proteinuria • antiphospholipid antibody syndrome or myeloproliferative diseases (polycythemia vera and essential thrombocythemia) • inability to ambulate • use of hormone-based contraceptives (including oral, transdermal patch, vaginal ring, and injectables) ≤16 weeks prior to Day 1, peri- and postmenopausal hormone replacement therapy ≤16 weeks prior to Day 1. Note: Use of intrauterine device (IUD) with levonorgestrel (single hormone) or copper (non-hormonal) is allowed.
18. ALT or AST >2.5×ULN at Screening.
19. Any contraindications to muscle biopsy.
20. Any contraindications to MRI.
21. History of any illness or any clinical condition that, in the opinion of the PI, might confound the results of the study or pose an additional risk in administering study drug to the subject. This may include, but is not limited to, a history of relevant drug or food allergies; history of cardiovascular or central nervous system disease; neuromuscular diseases except FSHD (eg, myopathy, neuropathy, neuromuscular junction disorders); or clinically significant history of mental disease. a. In the case of an upper respiratory infection within 7 days of first dose, PI may elect to extend Screening period such that the first dose is given within ≤7 days following clinical resolution of the infection.
22. For subjects who are on drug(s) or supplements that may affect muscle function, as determined by the treating physician, or that are listed in Section 8.2.3, subjects must be on a stable dose of that drug(s) or supplement for at least 28 days prior to the first dose of study drug and with no plans to change dose or treatment regimens during the duration of the study. Changes to the dose or treatment discontinuation during the study can only be done for medical reasons as part of standard management by the treating physician with clear documentation and notification to the sponsor.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence, frequency, and severity of treatment-emergent adverse events (TEAEs) in subjects with FSHD1 over time through end of study (EOS) at Day 90 (Part 1) or Day 360 (Part 2)

Secondary endpoints 2

1. Plasma PK of ARO-DUX4 in subjects with FSHD1
2. Urinary excretion of ARO-DUX4 in subjects with FSHD1

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sarepta Therapeutics Inc.

Sponsor organisation

Sarepta Therapeutics Inc.

Address

215 1st Street

City

Cambridge

Postcode

02142-1213

Country

United States

Scientific contact point

Organisation

Arrowhead Pharmaceuticals Inc.

Contact name

Jiyeon Denninger

Public contact point

Organisation

Arrowhead Pharmaceuticals Inc.

Contact name

Jiyeon Denninger

Third parties 21

Locations

4 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 85 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications