A Phase 2, Open-Label, Single Dose Level, 12-Week Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of AT1001 in Patients With Fabry Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 4
- 主要终点
- Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
Study to evaluate the safety, tolerability, and pharmacodynamics of migalastat hydrochloride (HCl) (migalastat) and how migalastat works in participants with Fabry disease.
详细描述
This was a Phase 2, open-label study in male participants with Fabry disease. The study consisted of a 4-week screening period during which participants' genotype was assessed for α-galactosidase A (α-Gal A) activity in response to migalastat via an in vitro assay. Participants were required to have α-Gal A activity responsive to migalastat. The study consisted of a 12-week treatment period, followed by an optional 36-week extension period. Participants received migalastat 150 milligrams (mg) once every other day (QOD) for 12 weeks during the treatment period. Participants could then opt to participate in the extension period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Males between 18 and 65 years of age (inclusive)
- •Hemizygous for Fabry disease
- •Had a confirmed diagnosis of Fabry disease with a documented missense gene mutation (individual or familial)
- •Had enhanceable enzyme activity based on in vitro tests
- •Had documented evidence of cardiac and/or renal dysfunction (for example, abnormal electrocardiogram (ECG), left ventricular hypertrophy, renal insufficiency) and/or cerebral tissue dysfunction documented by evidence of stroke and/or peripheral nervous tissue dysfunction (for example, intolerance to heat/cold, decrease of perspiration)
- •Must have been previously untreated by enzyme replacement therapy (ERT) or substrate depletion for Fabry disease or were able to stop ERT for at least 18 weeks or up to three months, and be willing to undergo two kidney and three skin biopsies
- •Agreed to be sexually abstinent or use a condom with spermicide when engaging in sexual activity during the course of the study and for a period of 30 days following their completion of the study
- •Were willing and able to sign an informed consent form
排除标准
- •History of significant disease other than Fabry disease
- •History of organ transplant
- •Serum creatinine >2 mg per deciliter on Day -2
- •Screening 12-lead ECG demonstrating corrected QT interval >450 milliseconds prior to dosing
- •Pacemaker or other contraindication for magnetic resonance imaging (MRI) scanning
- •Took any of the following prohibited medications: Fabrazyme® (agalsidase beta), Replagal™ (agalsidase alfa), Glyset® (miglitol), Zavesca® (miglustat), or any experimental therapy for any indication
- •Participated in a previous clinical trial in the last 30 days
- •Any other condition, which, in the opinion of the investigator, would jeopardize the safety of the participant or impact the validity of the study results
研究组 & 干预措施
Migalastat
Migalastat 150 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week extension period.
干预措施: migalastat HCl (Drug)
结局指标
主要结局
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
时间窗: Day 1 (after dosing) through Week 48 (end of extension period)
TEAEs were defined as any adverse event with a start date on or after administration of study drug or pre-existing conditions that worsened on or after the start of the first study drug administration (on Day 1). A severe adverse event was defined as an adverse event that was incapacitating and required medical intervention. The number of participants who experienced one or more severe TEAEs after dosing on Day 1 through Week 48 is presented. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
次要结局
- α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 12, And Week 48(Baseline, Week 12 (end of treatment period), Week 48 (end of extension period))