A Randomized, Open-label Study To Assess the Safety and Tolerability of AT2101 in Treatment-naive Adult Patients With Type 1 Gaucher Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 19
- 主要终点
- Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
This study evaluated the safety and tolerability of afegostat tartrate in participants with type 1 Gaucher disease who were not receiving enzyme replacement therapy (ERT) or substrate reduction therapy (SRT).
详细描述
This was a Phase 2, open-label study in participants with Gaucher disease, a lysosomal storage disorder. Afegostat tartrate (also known as AT2101 or isofagomine tartrate) is designed to act as a pharmacological chaperone by selectively binding to misfolded β-glucocerebrosidase (GCase) and helping it fold correctly, intended to restore GCase activity. The study consisted of a 21-day screening period, a 24-week treatment period, and follow-up visit (Day 183, end-of-study). Participants were randomized in a 1:1 ratio to 1 of 2 treatment regimens for afegostat tartrate (3 days on treatment/4 days off or 7 days on treatment/7 days off).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of type 1 Gaucher disease with a known genotype and a documented missense gene mutation in at least 1 of the 2 gene-encoding β-glucosidase (GBA) alleles
- •Clinically stable
- •Treatment naïve to ERT and SRT or had not received ERT or SRT in the 12 months before screening
- •Willing to not initiate ERT or SRT treatment during study participation
- •Male or female participants, 18 to 74 years old, inclusive
- •At the screening period (Day -21 to Day -1), participants must have met at least 2 of the following criteria: platelet count of ≤150,000 per microliter, hemoglobin ≤12 grams/deciliter (g/dL) for females and ≤13 g/dL for males, liver volume ≥1.25 multiples of normal (MN), and spleen volume ≥2 MN
- •All participants of reproductive potential were required to practice an acceptable method of contraception
- •Provided written informed consent to participate in the study
排除标准
- •A clinically significant disease other than Gaucher disease, severe complications from Gaucher disease, or serious intercurrent illness that precluded participation in the study in the opinion of the investigator
- •During the screening period, had any clinically significant findings as deemed by the investigator
- •Partial or total splenectomy
- •Documentation of moderate or severe pulmonary hypertension, defined as pulmonary arterial pressure >35 millimeters of mercury (mmHg) or significant Gaucher-related lung disease
- •History of allergy or sensitivity to the study drug or any excipients, including any prior serious allergic reaction to iminosugars
- •Pacemaker or other contraindication for magnetic resonance imaging (MRI) scanning
- •Pregnant or breast-feeding
- •Current/recent drug or alcohol abuse
- •Treatment with any investigational product in the last 90 days before study entry
- •Treatment in the previous 90 days with any drug known to have a well-defined potential for toxicity to a major organ
- •Presence of symptoms of gastrointestinal, liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs
研究组 & 干预措施
Afegostat Tartrate Treatment Regimen 1
For the first 2 weeks, afegostat tartrate was administered orally at a dose of 225 milligrams (mg) once daily (QD) for 7 consecutive days, followed by no study medication for 7 consecutive days. After 2 weeks, participants then took 225 mg afegostat tartrate QD for 3 consecutive days, followed by no study medication for 4 consecutive days. This 3-days-on/4-days-off treatment regimen was followed for 22 weeks.
干预措施: afegostat tartrate (Drug)
Afegostat Tartrate Treatment Regimen 2
Afegostat tartrate was administered orally at a dose of 225 mg QD for 7 consecutive days, followed by no study medication for 7 consecutive days. This 7-days-on/7-days-off treatment regimen was followed for 24 weeks.
干预措施: afegostat tartrate (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 Day 183
A TEAE was defined as any adverse event (AE) 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 AE defined as an AE that was incapacitating and required medical intervention. The number of participants who experienced 1 or more severe TEAEs after dosing on Day 1 through the end of follow-up (Day 183) is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
次要结局
- Change From Baseline To End Of Treatment In β-glucocerebrosidase (GCase) Levels In White Blood Cells (WBC)(Baseline, Day 169)