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Dose-Ranging Study of ST-920, an AAV2/6 Human Alpha Galactosidase A Gene Therapy in Subjects With Fabry Disease (STAAR)
Bu çalışma, Fabry hastalığı (Fabry disease) olan bireylerde ST-920 adlı bir gen terapisini incelemektedir; bu tedavi, eksik olan alfa galaktozidaz A enzimini üretmesi için AAV2/6 taşıyıcısı aracılığıyla vücuda gen aktarmayı amaçlamaktadır. Fabry hastalığı tanısı doğrulanmış ve belirli belirtileri bulunan 18 yaş ve üzeri bireyler katılabilmiştir. Çalışma Faz 1/Faz 2 aşamasında yürütülmüş ve tamamlanmıştır.
Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.
Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.
Inclusion Criteria: * ≥ 18 years of age * Documented diagnosis of Fabry disease * One or more of the following symptoms: i) cornea verticillata, ii) acroparesthesia, iii) anhidrosis, iv) angiokeratoma * Subject must be fully vaccinated (as per the Centers for Disease Control and Prevention (CDC) definition in the US and as per local guidelines in other countries) for Coronavirus Disease (COVID-19) at least one month prior to dosing Additional Inclusion Criteria: Renal Cohort: * Screening estimated glomerular filtration rate (eGFR) value between 40-90 mL/min/1.73 m² * Linear negative eGFR slope (estimated from at least 3 serum creatinine values within 18 months, including the value obtained during screening visit) of ≥ 2 mL/min/1.73m²/year Cardiac Cohort: • Left ventricular hypertrophy (LVH) in 2D echocardiography or cardiac magnetic resonance imaging (CMR) defined as an end diastolic septum and posterior wall thickness ≥12 mm with no other explanation for LVH, OR presentation with cardiac changes indicative of disease progression such as decreased global longitudinal strain on 2D strain echocardiography or low native T1 mapping on CMR Exclusion Criteria: * Neutralizing antibodies to AAV6 * eGFR \< 40 ml/min/1.73m2 * New York Heart Association Class III or higher * Active infection with hepatitis A, B or C, human immunodeficiency virus (HIV) or tuberculosis (TB) * History of liver disease such as clinically significant steatosis, fibrosis, non-alcoholic steatohepatitis (NASH) and cirrhosis, biliary disease within 6 months of informed consent; except for Gilbert's syndrome * Elevated circulating serum alpha fetoprotein (AFP) * Recent or recurrent hypersensitivity response to enzyme replacement therapy (ERT) within within 6 months prior to consent * Current or history of systemic (IV or oral) immunomodulatory agents, or biologics or steroid use in the past 6 months prior to consent (topical treatment and inhaled allowed). * Contraindication to use of corticosteroids * History of malignancy except for non-melanoma skin cancer and localized prostate cancer treated with curative intent * Recent history of alcohol or substance abuse * Participation in investigational interventional drug or medical device study throughout the duration of this study and within previous 3 months prior to consent * Prior treatment with a gene therapy product * Known hypersensitivity to components of ST-920 formulation * Any other reason that, in the opinion of the Site Investigator or Medical Monitor, would render the subject unsuitable for participation in the study including but not limited to risk of COVID-19 infection Additional exclusion criteria for: Renal cohort: * History of renal dialysis or transplantation * History of acute kidney insufficiency in the 6 months prior to screening * Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated within 4 weeks prior to screening or changed ACE inhibitor or ARB dose in the 4 weeks prior to screening * Urine protein to creatinine ratio (UPCR) \> 0.5 g/g who are not being treated with an ACE inhibitor or ARB Cardiac cohort: * Significant cardiac fibrosis defined by late gadolinium enhancement on CMR * Any contraindications to CMR as per local hospital/institution guidelines * Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated within 4 weeks prior to screening or changed ACE inhibitor or ARB dose in the 4 weeks prior to screening * New York heart association (NYHA) Class IV