A Multicenter, Open-label Extension Study of Velaglucerase Alfa Enzyme Replacement Therapy in Japanese Patients With Gaucher Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 5
- 试验地点
- 5
- 主要终点
- Number of Participants With Drug-related Adverse Events (AEs), Infusion-related AEs, and Serious AEs (SAEs)
研究概览
简要总结
Gaucher disease is an inherited deficiency of the lysosomal enzyme glucocerebrosidase (GCB) that leads to progressive accumulation of glucocerebroside within macrophages and subsequent tissue and organ damage; typically of the liver, spleen, bone marrow, and brain. Type 1 Gaucher disease affects an estimated 30,000 persons worldwide and is the most common. Type 1 Gaucher disease does not involve the central nervous system. Patients with Type 2 Gaucher disease present with acute neurological deterioration, which leads to early death. Those with Type 3 disease typically display a more sub-acute neurological course, with later onset and slower progression.
The primary objective of this study is to evaluate the long-term safety of every other week (EOW) dosing of velaglucerase alfa in Japanese patients with Gaucher disease who completed study HGT-GCB-087 and elected to continue treatment with velaglucerase alfa.
Velaglucerase alfa has been developed and approved as an enzyme replacement therapy for Type 1 Gaucher disease.
详细描述
Gaucher disease is an inherited deficiency of the lysosomal enzyme glucocerebrosidase (GCB) that leads to progressive accumulation of glucocerebroside within macrophages and subsequent tissue and organ damage; typically of the liver, spleen, bone marrow, and brain.
Gaucher disease has been designated in the list of Specified Rare and Intractable Diseases by Specified Disease Treatment Research Program of Ministry of Health, Labor and Welfare (MHLW) as one of "lysosomal storage diseases" since 2001. Gaucher disease is also designated in the Medical Aid Program for Specified Categories of Chronic Pediatric Diseases.
The prevalence of mutations and the phenotype of patients with Gaucher disease in Japan differs from that in non-Japanese populations. Some patients with type 1 Gaucher disease in Japan have more severe and progressive disease compared to non-Japanese patients and the disease is characterized by an earlier onset of symptoms.
Velaglucerase alfa, a highly-purified form of the naturally occurring enzyme glucocerebrosidase, has been developed as an enzyme replacement therapy for Gaucher disease for the symptoms (anemia, thrombocytopenia, hepatomegaly, splenomegaly, and bone manifestation).
The primary objective of this study is to evaluate the long-term safety of every other week (EOW) dosing of velaglucerase alfa in Japanese patients with Gaucher disease who completed study HGT-GCB-087 and elected to continue treatment with velaglucerase alfa.
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
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient has completed treatment with EOW velaglucerase alfa through Week 51 of study HGT-GCB-
- •Female patients of child bearing potential must agree to use a medically acceptable method of contraception at all times during the study.
- •The patient, the patient's parent(s)or legal guardian(s) has provided written informed consent that has been approved by the Institutional Review Board/Independent Ethics Committee(IRB/IEC)
- •The patient must be sufficiently cooperative to participate in this clinical study as judged by the Investigator.
排除标准
- •The patient has received treatment with any investigational drug, other than velaglucerase alfa, or investigational device within 30 days prior to study entry; such use during the study is not permitted.
- •The patient, patient's parent(s), or patient's legal guardian(s) is/are unable to understand the nature, scope, and possible consequences of the study.
- •The patient has a significant comorbidity, as determined by the Investigator that might affect study data or confound the study results.
- •The patient is unable to comply with the protocol as determined by the Investigator.
研究组 & 干预措施
velaglucerase alfa
15 to 60 U/kg, EOW via intravenous infusion
干预措施: velaglucerase alfa (Drug)
结局指标
主要结局
Number of Participants With Drug-related Adverse Events (AEs), Infusion-related AEs, and Serious AEs (SAEs)
时间窗: From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
An AE was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered related to investigational product. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. An infusion-related AE was defined as an AE that started either during or within 12 hours after the start of the infusion and that was judged as possibly or probably related to investigational product.
Number of Participants Using Concomitant Medication
时间窗: From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
Number of Participants With Abnormal and Clinically Significant Laboratory Test Results
时间窗: From Week 65 until the end of study (Week 155)
Laboratory test results were considered abnormal and clinically significant at the discretion of the investigator.
Number of Participants With Positive Anti-Velaglucerase Alfa Antibodies
时间窗: From Week 65 until the end of study (Week 155)
Serum samples were collected for all participants for determination of anti-velaglucerase alfa antibodies every 12 weeks.
次要结局
- Change From Baseline in Bone Marrow Burden (BMB) Score at Week 103(Baseline, Week 103)
- Change From Baseline in Plasma Chitotriosidase Levels at Week 101(Baseline, Week 101)
- Change From Baseline in Hemoglobin Concentration at Week 101(Baseline, Week 101)
- Change From Baseline in Platelet Count at Week 101(Baseline, Week 101)
- Change From Baseline in Liver Volume Normalized to Body Weight at Week 103(Baseline, Week 103)
- Change From Baseline in Skeletal Age at Week 103: Z-Score(Baseline, Week 103)
- Number of Participants With Change From Baseline in Neurological Status at Week 103(Baseline, Week 103)
- Change From Baseline in Chemokine [C-C Motif] Ligand 18 (CCL18) Levels at Week 101(Baseline, Week 101)
- Change From Baseline in Spleen Volume Normalized to Body Weight at Week 103(Baseline, Week 103)
- Change From Baseline in Bone Mineral Density (BMD) at Week 103: Z Score(Baseline, Week 103)
- Change From Baseline in Bone Mineral Density (BMD) at Week 103: T-Score(Baseline, Week 103)
- Change From Baseline in Growth Velocity at Week 101 : Height Z-Score(Baseline, Week 101)