Open-label, Non Comparative, Multi-center Study to Evaluate the Long Term Efficacy, Safety and Tolerability of Oral Miglustat as a Maintenance Therapy After a Switch From Enzyme Replacement Therapy in Adult Patients With Stable Type 1 Gaucher Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 42
- 主要终点
- Liver Volume at Baseline and at End of Treatment
研究概览
简要总结
Although miglustat has been approved as a treatment for mild to moderate type 1 Gaucher disease in patients who are unsuitable for enzyme replacement therapy (ERT), more data are required to establish the long term efficacy, safety and tolerability of miglustat in maintaining diseases stability after a switch from ERT.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females aged 18 years or older
- •Type 1 Gaucher disease, diagnosed by glucocerebrosidase assay or molecular analysis of the glucocerebrosidase gene.
- •Treatment with ERT for at least 3 years, with a stable dose regimen for at least the last 6 months.
- •Clinically and biologically stable disease for the previous 2 years, with at least 2 time points assessments (including baseline as one potential time point), defined as:
- •Stable organomegaly (assessed by magnetic resonance imaging (MRI) or computed tomography (CT)):
- •Liver volume within 10% of the mean.
- •Spleen volume within 10% of the mean.
- •Free of progressive symptomatic documented bone disease.
- •Hemoglobin levels > 11g/dl
- •Mean platelet count > 100x10^9 /l.
- •Chitotriosidase activity within 20% of the mean.
- •If chitotriosidase is not available (in the case of chitotriosidase deficiency, or if it was not determined), other relevant biomarkers (e.g., angiotensin converting enzyme (ACE), tartrate resistant acid phosphatase (TRAP) and ferritin) could be considered.
- •Written informed consent.
排除标准
- •History or evidence of oculomotor gaze palsy, ataxia or other clinical manifestations typically associated with neuronopathic type 3 Gaucher disease.
- •Not ambulant patients, or with progressive symptomatic documented bone disease.
- •Splenectomy before 18 years of age for splenomegaly and/or thrombocytopenia.
- •Peripheral polyneuropathy (not mononeuropathy) documented with both clinical signs and symptoms, and electrodiagnostic (EDX).
- •Patients (males and females) who do not agree to use reliable contraception throughout the study and for 3 months after cessation of miglustat treatment.
- •Female patients who are pregnant or breast feeding, or without pregnancy test prior to Day
- •History of significant lactose intolerance.
- •Clinically significant diarrhea (>3 liquid stools per day for >7 days) without definable cause within 6 months prior to Day 1, or a history of clinically relevant gastrointestinal disorders.
- •History of cataracts or known increased risk of cataract formation.
- •Severe renal impairment i.e., with a creatinine clearance <30 ml/min/1.73m^2
- •Concomitant active medical condition such as human immunodeficiency virus (HIV) or hepatitis B/C that would render patients unsuitable for study.
- •Previous treatment with miglustat.
研究组 & 干预措施
Open-label miglustat
Oral administration of miglustat 100 mg t.i.d. for a period of 2 years
干预措施: Miglustat (Drug)
结局指标
主要结局
Liver Volume at Baseline and at End of Treatment
时间窗: Baseline and end of treatment (Month 24)
Liver volume was assessed at baseline and end of treatment by magnetic resonance imaging. Imputation methods for patients with missing values at Month 24 were applied as follows: if a patient had at least 640 days of treatment with the study drug, the last observation that was not more than 2 days after the end of treatment was carried forward. If a patient had discontinued study drug before Day 640, the 'worst' within-patient value not more than 2 days after the end of treatment was used to impute the missing value.
Mean Within-patient Percent Change From Baseline in Liver Volume
时间窗: End of treatment (Month 24)
Liver volume was assessed at baseline and end of treatment by magnetic resonance imaging. Imputation methods for patients with missing values at Month 24 were applied as follows: if a patient had at least 640 days of treatment with the study drug, the last observation that was not more than 2 days after the end of treatment was carried forward. If a patient had discontinued study drug before Day 640, the 'worst' within-patient value not more than 2 days after the end of treatment was used to impute the missing value.
次要结局
- Spleen Volume at Baseline and End of Treatment(Baseline and end of treatment (Month 24))
- Mean Percent Change From Baseline in Spleen Volume(End of treatment (Month 24))