A Phase 2, Open-Label, Single Dose Level, 24-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
- 5
- 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) 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' galactosidase (GLA) genotype was assessed for α-galactosidase A (α-Gal A) activity in response to migalastat. Participants were required to have α-Gal A activity responsive to migalastat. The study consisted of a 24-week treatment period, followed by an optional 24-week extension period. Participants received migalastat once every other day (QOD) for 24 weeks during the treatment period and the optional 24-week extension for a total treatment duration of up to 48 weeks.
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)
- •Were previously untreated by enzyme replacement therapy (ERT) or substrate depletion for Fabry disease, or if ERT or other specific treatment for Fabry disease was administered, were able to stop ERT for at least 30 weeks.
- •Were willing to undergo 2 kidney and 3 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 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 (for example, end-stage renal disease; Class III or IV heart disease [per the New York Heart Association classification]; current diagnosis of cancer, except for basal cell carcinoma of the skin; diabetes [unless hemoglobin A1c ≤8]; or neurological disease that would have impaired the participant's ability to participate in the study)
- •History of organ transplant
- •Serum creatinine >176 millimole per deciliter on Day -2
- •Screening 12-lead ECG demonstrating corrected QT interval >450 milliseconds prior to dosing
- •Taking a medication prohibited by the protocol: 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 milligrams (mg) was administered orally QOD during the 24-week treatment period and then during the optional 24-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
TEAEs were defined as any adverse event with 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 24, And Week 48(Baseline, Week 24 (end of treatment period), Week 48 (end of extension period))