ADS-010 for Facioscapulohumeral muscular dystrophy (FSHD1)

Inclusion criteria

• {"criterion_text":"-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."}
• {"criterion_text":"-Clinical severity score (CSS) between 3 and 8 (scale, 0 to 10)"}
• {"criterion_text":"-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%."}
• {"criterion_text":"-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."}
• {"criterion_text":"-Able and willing to provide written informed consent prior to the performance of any study specific procedures."}
• {"criterion_text":"-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."}
• {"criterion_text":"-A 12-lead ECG at Screening with no abnormalities that may compromise the subject’s safety in this study per PI discretion."}
• {"criterion_text":"-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."}
• {"criterion_text":"-Must be willing and able to comply with all study assessments and adhere to the protocol schedule."}

Exclusion criteria

• {"criterion_text":"-Is unable to comply with the study requirements, including the number of required visits to the clinical site."}
• {"criterion_text":"-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."}
• {"criterion_text":"-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."}
• {"criterion_text":"-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."}
• {"criterion_text":"-Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 calculated by using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation (CKD-EPI)."}
• {"criterion_text":"-Current concomitant use of theophylline (including duration of study)."}
• {"criterion_text":"-History of thromboembolic events including deep vein thrombosis, thrombotic stroke, pulmonary embolism, or atrial thrombi."}
• {"criterion_text":"-Thrombocytopenia (platelet count less than the lower limit of normal) at Screening."}
• {"criterion_text":"-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."}
• {"criterion_text":"-ALT or AST >2.5×ULN at Screening."}
• {"criterion_text":"-Any contraindications to muscle biopsy."}
• {"criterion_text":"-HIV infection, as shown by the presence of anti-HIV antibody (seropositive) at Screening."}
• {"criterion_text":"-Any contraindications to MRI."}
• {"criterion_text":"-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."}
• {"criterion_text":"-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."}
• {"criterion_text":"-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)."}
• {"criterion_text":"-Uncontrolled hypertension (blood pressure >160/100 mmHg at Screening, confirmed by repeat)."}
• {"criterion_text":"-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."}
• {"criterion_text":"-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)."}
• {"criterion_text":"-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."}
• {"criterion_text":"-History of major surgery within 3 months of Screening."}
• {"criterion_text":"-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])."}

Primary endpoints

• {"endpoint_text":"-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)","definition_or_measurement_approach":"TEAEs will be recorded over time through EOS at Day 90 for Part 1 and Day 360 for Part 2; standard safety reporting of incidence, frequency and severity of TEAEs as collected during study visits and follow-up."}

Secondary endpoints

• {"endpoint_text":"-Plasma PK of ARO-DUX4 in subjects with FSHD1","definition_or_measurement_approach":"Plasma pharmacokinetics (PK) of ARO-DUX4 measured in blood samples per PK sampling schedule (specific sampling times not provided in JSON)."}
• {"endpoint_text":"-Urinary excretion of ARO-DUX4 in subjects with FSHD1","definition_or_measurement_approach":"Measurement of urinary excretion of ARO-DUX4 in urine samples per study schedule (specifics not provided in JSON)."}

Methods

• Recruitment arrangements documents and country-specific recruitment materials present (titles indicate use of patient brochure, patient poster, and social media posts).
• Country/language-specific recruitment materials available: Germany (DE recruitment brochure, poster, social media post), Italy (IT recruitment brochure, poster, social media post), Netherlands (NL recruitment arrangements, CHDR materials), Spain (ES recruitment arrangements, patient brochure/poster, social media).
• Recruitment via participating clinical sites/centres (listed trial sites in Germany, Italy, Spain, Netherlands).

Spain

Earliest CTIS Part Ii Submission Date

11-07-2024

Latest Decision Or Authorization Date

26-01-2026

Processing Time Days

564

Number Of Sites

3

Number Of Participants

5

Netherlands

Earliest CTIS Part Ii Submission Date

31-07-2024

Latest Decision Or Authorization Date

13-01-2026

Processing Time Days

531

Number Of Sites

1

Number Of Participants

12

Italy

Earliest CTIS Part Ii Submission Date

18-07-2024

Latest Decision Or Authorization Date

21-01-2026

Processing Time Days

552

Number Of Sites

3

Number Of Participants

17

Germany

Earliest CTIS Part Ii Submission Date

19-06-2024

Latest Decision Or Authorization Date

12-02-2026

Processing Time Days

603

Number Of Sites

2

Number Of Participants

10

Primary sponsor

Full Name

Sarepta Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Novotech Clinical Research (Cyprus) Limited

Responsibilities

codes: 1,12,13,2,5

Name

Novotech (Australia) Pty Limited

Responsibilities

codes: 1,12,13,2,5

Name

Medpace Belgium

Name

Fortrea Inc.

Responsibilities

code: 8

Name

Scout Clinical

Responsibilities

Expense Reimbursement Management

Name

Harmony Clinical Research

Responsibilities

codes: 1,12,2

Third parties

• {"country":"United States","full_name":"Keystone Bioanalytical Inc.","duties_or_roles":"PK and biopsy analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Sarepta Therapeutics Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Charles River Laboratories Montreal ULC","duties_or_roles":"ADA analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"TMF management","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Cyprus","full_name":"Novotech Clinical Research (Cyprus) Limited","duties_or_roles":"codes: 1,12,13,2,5","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Expense Reimbursement Management","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Belgium","full_name":"Medpace Belgium","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Emsere B.V.","duties_or_roles":"Equipment supply","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Evidenze Health S.r.l.","duties_or_roles":"codes: 1,12,2","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"code: 8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medpace Imaging Core Lab","duties_or_roles":"EEG vendor","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"serum biomarker and biopsy analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Lineagen Inc.","duties_or_roles":"Central Lab services (Pre-Screening Genetic Testing)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Bioniks","duties_or_roles":"providing the equipment for and data analysis for the reachable workspace assessment","organisation_type":"Pharmaceutical company"}
• {"country":"Australia","full_name":"Novotech (Australia) Pty Limited","duties_or_roles":"codes: 1,12,13,2,5","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"BiognoSYS AG","duties_or_roles":"serum biomarker analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Neogenomics Laboratories Inc.","duties_or_roles":"laboratory","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Belgium","full_name":"Harmony Clinical Research","duties_or_roles":"codes: 1,12,2","organisation_type":"Pharmaceutical company"}