NCT04046224已完成1 期
A Phase I/II, Multicenter, Open-Label, Single-Dose, Dose-Ranging Study to Assess the Safety and Tolerability of ST-920, an AAV2/6 Human Alpha Galactosidase A Gene Therapy, in Subjects With Fabry Disease (STAAR)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 21
- 主要终点
- Incidence of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
This is the first in human treatment with ST-920, an adeno-associated virus (AAV2/6) vector encoding the complementary deoxyribonucleic acid (cDNA) for human a-Gal A. The purpose of this study is to evaluate the safety and tolerability of ascending doses of ST-920. ST-920 aims to provide stable, long-term production of α-Gal A at therapeutic levels in subjects with Fabry disease. The constant production of α-Gal A in humans should, importantly, enable reduction and potentially clearance of Fabry disease substrates Gb3 and lyso-Gb3. On Day 1, patients will be infused intravenously with a single dose of ST-920 and followed for a period of 52 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 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
排除标准
- •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
研究组 & 干预措施
Sequential dose escalation
Experimental
ST-920 is administered as a single infusion:
- Cohort 1: 0.5e13 vg/kg
- Cohort 2: 1.0e13 vg/kg
- Cohort 3: 3.0e13 vg/kg
- Cohort 4: 5.0e13 vg/kg
干预措施: ST-920 (Biological)
Expansion Cohorts
Experimental
- Anti Alpha-Gal A Antibody Positive Cohort
- Anti Alpha-Gal A Antibody Negative Cohort
- Female Cohort
- Renal Cohort
- Cardiac Cohort
干预措施: ST-920 (Biological)
结局指标
主要结局
Incidence of treatment-emergent adverse events (TEAEs)
时间窗: Up to 12 months after the ST-920 infusion
Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in subjects who receive ST-920 as assessed by Common Terminology Criteria for Adverse Events (CTCAE)
Incidence of Treatment-emergent Adverse Events (TEAEs) - All
时间窗: Up to 12 months after the ST-920 infusion
All incidences of Treatment-Emergent Adverse Events (TEAEs) in subjects who receive ST-920 as assessed by Common Terminology Criteria for Adverse Events (CTCAE)
Incidence of Treatment-emergent Adverse Events (TEAEs) - Related to ST-920
时间窗: Up to 12 months post ST-920 infusion
Incidences of Treatment-Emergent Adverse Events (TEAEs) directly related to ST-920 in subjects who receive ST-920 as assessed by Common Terminology Criteria for Adverse Events (CTCAE)
Incidence of Treatment-emergent Adverse Events (TEAEs) - Serious
时间窗: Up to 12 month post ST-920 infusion
All incidences of serious Treatment-Emergent Adverse Events (TEAEs) in subjects who receive ST-920 as assessed by Common Terminology Criteria for Adverse Events (CTCAE)
Incidence of Treatment-emergent Adverse Events (TEAEs) - Any TEAEs Leading to Study Discontinuation or Withdrawal
时间窗: Up to 12 month post ST-920 infusion
All incidences of Treatment-Emergent Adverse Events (TEAEs) that lead to study discontinuation or withdrawal in subjects who receive ST-920 as assessed by Common Terminology Criteria for Adverse Events (CTCAE)
次要结局
- To Assess Alpha Gal-A Activity in Plasma Over Time(up to 12 months post ST-920 infusion)
研究者
研究点 (21)
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相关资讯
Sangamo's Isaralgagene Civaparvovec Nears Accelerated Approval as Fabry Disease Market Poised to Reach $5.92 Billion by 2035
- Sangamo Therapeutics' gene therapy ST-920 (isaralgagene civaparvovec) is advancing toward accelerated FDA approval with a BLA submission planned for the latter half of 2025, following positive Phase 1/2 STAAR trial data.
- The global Fabry disease treatment market was valued at USD 2.62 billion in 2025 and is projected to reach USD 5.92 billion by 2035, growing at a CAGR of 8.47%.
- Enzyme replacement therapy remains the standard of care with 76.10% market share in 2025, while gene therapies and oral chaperone treatments are expected to reshape the treatment landscape.
- In 2024, approximately 9,200 diagnosed prevalent cases of Fabry disease were estimated in the United States, representing 52% of the total across the seven major markets.
3 months agoSangamo Therapeutics' Fabry Disease Candidate ST-920 Gains Accelerated Approval Pathway• Sangamo Therapeutics' shares surged after the FDA agreed to a regulatory pathway for accelerated approval of isaralgagene civaparvovec (ST-920) for Fabry disease.
• The FDA will consider data from the Phase I/II STAAR trial, using the rate of decline in eGFR at 52 weeks as the primary basis for approval.
• Sangamo plans to submit a BLA in the second half of 2025, three years ahead of previous estimates, potentially bringing the treatment to patients sooner.
• Septerna, focusing on GPCR therapies, raised $288 million in an upsized IPO, highlighting renewed interest in biotech IPOs.last yearSangamo's Fabry Disease Gene Therapy ST-920 Poised for Accelerated FDA Approval• Sangamo Therapeutics' ST-920 (isaralgagene civaparvovec) gene therapy for Fabry disease may secure accelerated FDA approval based on Phase 1/2 data, potentially expediting market entry.
• The FDA has indicated that data from the ongoing STAAR trial, particularly the eGFR slope at 52 weeks, could serve as the primary basis for ST-920's accelerated approval.
• Interim data from the STAAR trial demonstrated that ST-920 was well-tolerated, led to sustained increases in alpha-Gal A enzyme levels, and reduced disease severity in patients.
• Patients on enzyme replacement therapy (ERT) were able to discontinue treatment while maintaining normal or above-normal alpha-Gal A levels, with significant improvements observed in kidney function (eGFR).last yearSangamo's Fabry Disease Gene Therapy ST-920 Receives Accelerated Approval Pathway from FDA- Sangamo Therapeutics' ST-920, a gene therapy for Fabry disease, gains FDA agreement for accelerated approval based on Phase 1/2 STAAR study data.
- The FDA will consider eGFR slope at 52 weeks as the primary endpoint for accelerated approval, potentially expediting the BLA submission to the second half of 2025.
- Data from the STAAR study showed statistically significant improvements in eGFR levels in patients treated with ST-920, supporting the accelerated approval pathway.
- The accelerated approval pathway could bring ST-920 to market approximately three years sooner than a traditional approval, addressing a significant unmet need.last year