NCT06270316招募中1 期
A Phase 1/2, Single Dose, Dose Ranging Study of Intravenous AAV5-GLA (AMT-191) in Adult Males With Classic Fabry Disease
UniQure Biopharma B.V.8 个研究点 分布在 1 个国家目标入组 12 人开始时间: 2024年6月5日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 12
- 试验地点
- 8
- 主要终点
- Evaluate the safety and tolerability of different dose levels of intravenously-administered AMT-191 in Participants with FD
研究概览
简要总结
The main goals of this clinical study are to characterize safety and PK/PD of AMT-191 i.e. if drug doses used in the study are safe and tolerable and to understand how it acts in the body of people with Fabry disease.
详细描述
In Fabry disease, the enzyme α-galactosidase A is deficient. AMT-191 is an investigational gene therapy that encodes a recombinant serotype 5 based adeno-associated viral vector (rAAV5). AMT-191 is designed to target the liver for production of the enzyme α-galactosidase A (αGAL). AMT-191 is delivered via a single (one-time) intravenous (IV) infusion.
In this first-in-human study of AMT-191, two or more dose levels will be tested.
All eligible participants will receive AMT-191 at one of the dose levels; there is no placebo in this study. The starting dose level is decided based on accepted rules for dose translation from preclinical (animal) studies to humans. Subsequent dose cohort levels are decided based on the review of safety, tolerability, and PK/PD results by an Independent Data Monitoring Committee and in agreement with the Sponsor.
Participants will be monitored through study site visits, blood tests, imaging questionnaires, and other assessments as per the study protocols.
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 50 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male of age ≥ 18 years and ≤50 years
- •Confirmed clinical diagnosis of classic Fabry disease (FD) defined as:
- •Absent or minimal αGAL A enzyme activity < 1% of mean normal measured in plasma regardless of variant status; OR
- •α-galactosidase A (GLA) pathogenic or likely pathogenic variant associated with classic FD phenotype identified on molecular genetic testing with plasma αGLA A enzyme activity below lower bound of the reference range (as measured at trough enzyme replacement therapy [ERT] levels).
- •eGFR ≥ 40 mL/min/1.73 m2
- •Suboptimal response after at least 12 months of enzyme replacement therapy (ERT) treatment. Suboptimal response is defined as plasma lyso-Gb3 ≥ 2.3 nanograms per milliliter (ng/mL) at Screening and one or both of the following:
- •Persistent moderate or severe neuropathic pain (intermittent or continuous) over a period of at least 3 months prior to consent
- •Presence of gastrointestinal symptoms (abdominal cramping, constipation, or diarrhea), reported by the Participant as moderate or severe and that are either persistent or occurring two or more times over the 12 weeks prior to consent
- •Weight ≤ 120 kilograms (kg)
排除标准
- •Any allergic hypersensitivity reaction to ERT or infusion reaction in the 12 months prior to consent that was of severity grade 3 or above based on Common Terminology Criteria for Adverse Events (CTCAE v5.0) and required emergency intervention for hypertension/hypotension to stabilize blood pressure or hypoxia OR any other life-threatening complication.
- •Proteinuria, with random urine protein/creatinine ratio (rUPCR) ≥1 mg/mg at Screening
- •Current use of chaperone therapy such as migalastat (Galafold®)
- •Malignancy within 5 years of Screening, except for basal or squamous cell carcinoma of the skin
- •Presence of chronic, active, or latent infection with hepatitis B or C, human immunodeficiency virus (HIV), or tuberculosis (TB) as assessed at the screening visit
- •Active or ongoing infection or any other significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, cardiovascular, hematological, GI, endocrine (such as diabetes mellitus with poor glycemic control), pulmonary, neurological, cerebral, or psychiatric disease, alcoholism, drug dependency, or any other psychological disorder that could, in the opinion of the Investigator, risk the safety of the Participant, or interfere with adherence to the protocol procedures or interpretation of results
- •Evidence of any liver disease, including hepatitis, fibrosis, cirrhosis of the liver, neoplastic lesion, or any known medical condition that could impact the intended transduction of the vector and/or expression and activity of the protein
- •History of kidney transplantation or currently on hemodialysis or peritoneal dialysis
- •Uncontrolled hypertension, defined as systolic blood pressure >140 millimeters of mercury (mmHg) (inclusive) and/or diastolic blood pressure outside the range of 60 to 85 mmHg (inclusive) at Screening, confirmed on at least 2 repeated measurements
- •Patients taking blood pressure medication to control blood pressure or proteinuria (eg, angiotensin-converting enzyme [ACE] inhibitors and angiotensin II receptor blockers [ARBs]) and have been titrated to a stable dose for at least 3 months prior to Screening are allowed in the study.
- •Glycated hemoglobin (HbA1c) at Screening ≥7%
- •Contraindication to systemic corticosteroid therapy or immunosuppressive therapy
- •Chronic steroid use, defined as ≥ 3 months of oral corticosteroid use within the 12 months prior to Screening
- •Screening laboratory values for renal and liver function that meet or exceed any of the following:
- •Alanine transaminase (ALT) > 2 x upper limit of normal for the testing laboratory (ULN)
- •Aspartate aminotransferase (AST) > 2 x ULN
- •Total Bilirubin > 2 x ULN (except if this is caused by Gilbert disease)
- •Alkaline phosphatase (ALP) > 2 x ULN
- •Creatinine > 2 x ULN
- •Screening laboratory values for hematologic and coagulation function that meet any of the following:
- •Hemoglobin < lower limit of normal (LLN) (as per reference laboratory ranges)
- •Platelet count < 150 x1000/μl
- •International normalized ratio (INR) >1.1
- •Soluble terminal complement complex (sC5b-9)>ULN
- •Significant anatomical abnormalities on renal ultrasound such as the presence of only 1 kidney, significant differences in kidney sizes between the right and left kidneys >1.5 centimeters (about 0.59 inch), or presence of kidney cysts
研究组 & 干预措施
Dose Ranging Cohort 1
Experimental
干预措施: AMT-191 (Drug)
Dose Ranging Cohort 2
Experimental
干预措施: AMT-191 (Drug)
Dose Ranging Cohort 3
Experimental
干预措施: AMT-191 (Drug)
结局指标
主要结局
Evaluate the safety and tolerability of different dose levels of intravenously-administered AMT-191 in Participants with FD
时间窗: 60 Months
Incidence of Treatment-Emergent Adverse Events (TEAE)
时间窗: 60 Months
次要结局
- Characterize the vector shedding of intravenously-administered AMT-191(60 Months)
研究者
研究点 (8)
Loading locations...
相似试验
招募中
1 期
A Phase 1/2, Dose-Exploration Study to Evaluate the Safety and Efficacy of BEAM-301 in Patients With Glycogen Storage Disease Type Ia (GSDIa)Glycogen Storage Disease Type IaNCT06735755Beam Therapeutics Inc.36
招募中
1 期
Safety and Efficacy Study of NGGT002 in Adult Patients With PhenylketonuriaPhenylketonuriasNCT06687733NGGT (Suzhou) Biotechnology Co., Ltd.18
终止
1 期
A Dose Escalation Study Evaluating the Safety and Tolerability of GDC-0032 in Participants With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma (NHL) and in Combination With Endocrine Therapy in Locally Advanced or Metastatic Hormone Receptor-Positive Breast CancerSolid CancersNon-Hodgkin's LymphomaNCT01296555Genentech, Inc.674
招募中
1 期
A Study of CM350 in Patients With Advanced Solid TumorsAdvanced Solid TumorNCT05263960Keymed Biosciences Co.Ltd248
已完成
1 期
A Study of ZN-e4 in Subjects With Epidermal Growth Factor Receptor Mutated Non-Small Cell Lung CancerCarcinoma, Non-Small-Cell LungNCT03446417Zeno Pharmaceuticals, Inc.34
相关资讯
uniQure's Fabry Disease Gene Therapy AMT-191 Advances as First Patient Cohort Completes Enrollment- uniQure has completed enrollment for the first cohort in its Phase I/IIa trial of AMT-191 gene therapy for Fabry disease, with safety review showing no significant concerns.
- The Independent Data Monitoring Committee has recommended proceeding with the second cohort, which will receive a higher dose of 300 trillion genome copies per kg compared to the first cohort's 60 trillion.
- The trial, taking place at sites in New York and Virginia, aims to evaluate AMT-191's potential to restore alpha-galactosidase A enzyme production in Fabry disease patients through 2027.last yearSangamo 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 yearuniQure's AMT-191 Receives FDA Orphan Drug Designation for Fabry Disease- The FDA has granted Orphan Drug Designation to uniQure's AMT-191, a gene therapy for Fabry disease, highlighting the need for innovative treatments.
- AMT-191 is a one-time, intravenously administered AAV5-based gene therapy designed to target the liver and produce the deficient GLA protein.
- A Phase I/IIa clinical trial is underway in the U.S. to assess the safety, tolerability, and early efficacy of AMT-191, with initial data expected in 2025.
- Orphan Drug Designation provides uniQure with incentives, including tax credits and market exclusivity, to support the development of AMT-191.last year