A Randomized, Open-label Study to Assess the Safety and Tolerability of Multiple Dose Levels and Multiple Dosing Regimens of AT2101 in Adult Patients With Type 1 Gaucher Disease Currently Receiving Enzyme Replacement Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 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 was conducted to test the safety and tolerability of afegostat tartrate in participants with type 1 Gaucher disease already receiving enzyme replacement therapy.
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 14-day screening period, a 28-day treatment period, and a 7-day wash-out period. Participants received 1 of 4 dosing regimens for afegostat tartrate.
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
- •Had a confirmed diagnosis of type 1 Gaucher disease with a known documented missense gene mutation in at least 1 of the 2 gene-encoding β-glucosidase alleles
- •Clinically stable
- •Male or female participants, 18 to 74 years old inclusive
- •All participants of childbearing potential used adequate birth control
- •Provided written informed consent to participate in the study
排除标准
- •Clinically significant disease, severe complications from Gaucher disease, or serious illness that precluded participation in the study in the opinion of the Investigator that compromised the safety of the participant or precluded the participant from completing the study
- •During the screening period, any clinically significant findings, as deemed by the Investigator
- •Partial or total splenectomy (removal of spleen) within the 2 years prior to study entry
- •History of pulmonary hypertension or Gaucher related lung disease
- •History of allergy or sensitivity to the study drug or any excipients, including any prior serious adverse reaction to iminosugars (for example, N-butyldeoxynojirimycin or miglustat)
- •Pregnant or breast-feeding
- •Current/recent drug or alcohol abuse
- •Treatment with any investigational product in the 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 or 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 25 milligrams (mg) once per day
Afegostat tartrate was administered orally during the 4-week treatment period.
干预措施: Afegostat tartrate (Drug)
Afegostat tartrate 150 mg once per day
Afegostat tartrate was administered orally once per day during the 4-week treatment period.
干预措施: Afegostat tartrate (Drug)
Afegostat tartrate 150 mg once every four days
Afegostat tartrate was administered orally once every 4 days during the 4-week treatment period.
干预措施: Afegostat tartrate (Drug)
Afegostat tartrate 150 mg once every seven days
Afegostat tartrate was administered orally once every 7 days during the 4-week treatment period.
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 35
TEAEs were defined as any adverse event (AE) with a start date on or after administration of the study drug (on Day 1). A severe AE was 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 7 days after the last dose of study drug (Day 35) 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 Beta-glucocerebrosidase (GCase) Levels In White Blood Cells (WBC)(Baseline, Day 28)