A Phase 3, Randomized, Multi-Center, Multi-National, Open-Label, Active Comparator Study to Evaluate the Efficacy and Safety of Genz-112638 in Patients With Gaucher Disease Type 1 Who Have Reached Therapeutic Goals With Enzyme Replacement Therapy (ENCORE)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 160
- 试验地点
- 34
- 主要终点
- Percentage of Participants Who Remained Stable for 52 Weeks During the Primary Analysis Period
研究概览
简要总结
This Phase 3 study was designed to confirm the efficacy and safety of eliglustat tartrate (Genz-112638) in participants with Gaucher disease type 1 who had reached therapeutic goals with enzyme replacement therapy (ERT).
详细描述
Gaucher disease is characterized by lysosomal accumulation of glucosylceramide due to impaired glucosylceramide hydrolysis. Gaucher disease type 1, which is the most common form, accounts for greater than (>) 90% of cases and does not involve the central nervous system (CNS). Typical manifestations of Gaucher disease type 1 include splenomegaly, hepatomegaly, thrombocytopenia, anemia, bone disease, and decreased quality of life. The disease manifestations are caused by the accumulation of glucosylceramide (storage material) in macrophages (called Gaucher cells) which have infiltrated the spleen and liver as well as other tissues.
Eliglustat tartrate is a small molecule drug developed as an oral therapy which acts to specifically inhibit production of this storage material in Gaucher cells.
This study was designed to determine the efficacy, safety, and PK of eliglustat tartrate in adult participants with Gaucher disease type 1 who had been stabilized on ERT.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The participant (and/or their parent/legal guardian) was willing and able to provide signed informed consent prior to any study-related procedures to be performed
- •The participant was at least 18 years old at the time of randomization
- •The participant had a confirmed diagnosis of Gaucher disease type 1
- •The participant had received treatment with ERT for at least 3 years. Within the 9 months prior to randomization, the participant had received a total monthly dose of 30 to 130 Units/kilogram for at least 6 months
- •The participant had reached Gaucher disease therapeutic goals prior to randomization
- •Female participants of childbearing potential must have had a documented negative pregnancy test prior to dosing. In addition, all female participants of childbearing potential must use a medically accepted form of contraception throughout the study
排除标准
- •The participant had a partial or total splenectomy within 3 years prior to randomization
- •The participant had received substrate reduction therapies for Gaucher disease within 6 months prior to randomization
- •The participant had Gaucher disease type 2 or 3 or was suspected of having Gaucher disease type 3
- •The participant had any clinically significant disease, other than Gaucher disease, including cardiovascular, renal, hepatic, gastrointestinal (GI), pulmonary, neurologic, endocrine, metabolic (e.g. hypokalemia, hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illnesses that may confound the study results or, in the opinion of the Investigator, may preclude participation in the study
- •The participant had tested positive for the human immunodeficiency virus (HIV) antibody, Hepatitis C antibody, or Hepatitis B surface antigen
- •The participant had received an investigational product within 30 days prior to randomization
- •The participant was pregnant or lactating
研究组 & 干预措施
Investigational
Eliglustat tartrate
干预措施: Eliglustat tartrate (Drug)
Imiglucerase
干预措施: Imiglucerase (Drug)
结局指标
主要结局
Percentage of Participants Who Remained Stable for 52 Weeks During the Primary Analysis Period
时间窗: Baseline up to Week 52
For a participant to be classified as stable, the participant must have remained stable in hematological parameters (hemoglobin levels and platelet counts) and organ volumes (spleen, when applicable, and liver volumes in multiples of normal \[MN\]). Stable hematological parameters were defined as hemoglobin level did not decrease more than (\>) 1.5 gram per deciliter (g/dL) from baseline and platelet count did not decrease \>25% from baseline. Stable organ volumes were defined as spleen volume (in MN) did not increase \>25% from baseline, if applicable, and liver volume (in MN) did not increase \>20% from baseline.
Percentage of Participants Who Remained Stable Annually for 4 Years During the LTTP
时间窗: Week 52 up to week 208
For a participant to be classified as stable, the participant must have remained stable in hematological parameters (hemoglobin levels and platelet counts) and organ volumes (spleen, when applicable, and liver volumes in MN). Stable hematological parameters were defined as hemoglobin level did not decrease \>1.5 g/dL from baseline and platelet count did not decrease \>25% from baseline. Stable organ volumes were defined as spleen volume (in MN) did not increase \>25% from baseline, if applicable, and liver volume did not increase \>20% from baseline.
次要结局
- Total T-Scores for Bone Mineral Density(Baseline)
- Absolute Change From Baseline in Total T-Scores for Bone Mineral Density at Week 52(Baseline, Week 52)
- Total Z-Scores for Bone Mineral Density(Baseline)
- Absolute Change From Baseline in Total Z-Scores for Bone Mineral Density at Week 52(Baseline, Week 52)
- Hemoglobin Level(Baseline)
- Absolute Change From Baseline in Hemoglobin Levels at Week 52(Baseline, Week 52)
- Percent Change From Baseline in Platelet Counts at Week 52(Baseline, Week 52)
- Percent Change From Baseline in Spleen Volume (MN) at Week 52(Baseline, Week 52)
- Percent Change From Baseline in Liver Volume (in MN) at Week 52(Baseline, Week 52)
- Absolute Change From Baseline in Total T-Scores for Bone Mineral Density at Week 208(Baseline, Week 208)
- Absolute Change From Baseline in Total Z-Scores for Bone Mineral Density at Week 208(Baseline, Week 208)
- Absolute Change From Baseline in Hemoglobin Levels at Week 208(Baseline, Week 208)
- Percent Change From Baseline in Platelet Counts at Week 208(Baseline, Week 208)
- Percent Change From Baseline in Spleen Volume (in MN) at Week 208(Baseline, Week 208)
- Percent Change From Baseline in Liver Volume (in MN) at Week 208(Baseline, Week 208)