A Phase IIa Study to Investigate Safety, Pharmacokinetics, and Efficacy of Odiparcil in Patients 16 Years and Above With Mucopolysaccharidosis (MPS) Type VI
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 4
- 主要终点
- Incidence of AEs/SAEs
研究概览
简要总结
Mucopolysaccharidoses (MPS) are a group of rare inherited disorders characterized by a deficiency of lysosomal enzymes responsible for the normal degradation of glycosaminoglycans (GAGs). Medical need for treatment of MPS is still very high due to the poor penetration of the recombinant enzymes into the blood brain barrier as well as the ocular barriers and into tissues that are poorly vascularized, such as cartilages and bones. Odiparcil is an orally active compound that allows the synthesis of soluble glycosaminoglycans (GAGs), mainly chondroitin sulfate (CS) and dermatane sulfate (DS). The neosynthesized solubles GAGs are then excreted in urine. By diverting endogenous GAG synthesis to the synthesis of soluble odiparcil linked GAGs, odiparcil should decrease the intracellular pool of GAGs and consequently decrease the lysosomal GAG accumulation.
The primary objective of the study is to assess the safety and efficacy of two doses of odiparcil in MPS VI patients and to provide evidence to enable the selection of the relevant dose of odiparcil for phase III study. The secondary objective of this study is to characterize the dose response, PK and PD of odiparcil.
详细描述
Study design: This phase IIa study consists of 2 parts performed sequentially: a preliminary safety assessment followed by the core study with a double-blind, randomized, dose-ranged cohort of patients receiving Enzyme Replacement Therapy (ERT) and an open-label cohort of patients not receiving ERT.
Preliminary safety assessment (N=2): open-label, escalating dose (2 doses) study. If acceptable safety profile is achieved, patients will be then included in the open-label arm of the core study.
Core study
Core study will be conducted on 2 populations in parallel:
- A first cohort (N=18): MPS VI patients receiving ERT assigned in 3 arms:
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Placebo
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Double-blind - placebo
2 tablets of placebo per os, twice daily (BID)
干预措施: Placebo (Other)
Open Label - odiparcil 1000 mg per day
2 tablets of odiparcil 250 mg per os, twice daily (BID)
干预措施: Odiparcil (Drug)
Double-blind - odiparcil 1000 mg per day
2 tablets of odiparcil 250 mg per os, twice daily (BID)
干预措施: Odiparcil (Drug)
Double-blind - odiparcil 500 mg per day
1 tablet of placebo and 1 tablet of odiparcil 250 mg per os, twice daily (BID)
干预措施: Odiparcil (Drug)
Double-blind - odiparcil 500 mg per day
1 tablet of placebo and 1 tablet of odiparcil 250 mg per os, twice daily (BID)
干预措施: Placebo (Other)
结局指标
主要结局
Incidence of AEs/SAEs
时间窗: 26 weeks
Incidence of AEs/SAEs, patient withdrawals from study due to AEs/SAEs,
12-lead ECG
时间窗: 26 weeks
Change from Baseline in ECG
Number of patients with modified clinical signs
时间窗: 26 weeks
Changes in physical examination and vital signs
Number of patients with modified biological values
时间窗: 26 weeks
Change from baseline in laboratory safety tests (coagulation, liver enzymes and crystalluria) 12-lead-ECG and bone biomarkers.
次要结局
- Mobility: 6-minute walk test(26 weeks)
- Mobility: range of motion of the shoulder(26 weeks)
- Audiology assessments(26 weeks)
- Ophthalmology assessments(26 weeks)
- ¨Pharmacodynamics: GAG concentrations(26 weeks)
- Pharmacodynamics: GAG concentrations(26 weeks)
- ¨Pharmacodynamics: anti-thrombin activity IIa(26 weeks)
- Mobility: 9-hole PEG test(26 weeks)
- Pain assessment(26 weeks)
- Respiratory function(26 weeks)
- Pharmacokinetics: odiparcil concentration in plasma(12 hours)
- ¨Pharmacodynamics: Thrombin Generation Assay (TGA)(26 weeks)
- Cardiac and vascular function(26 weeks)
- Quality of life questionnaires(26 weeks)