Multicenter, Open-Label, Multi-cohort Study to Evaluate Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Drug Product GNR 055 (JSC "GENERIUM", Russia) in Patients With Mucopolysaccharidosis Type II
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- AO GENERIUM
- 入组人数
- 32
- 试验地点
- 5
- 主要终点
- Incidence of Adverse events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
This is phase 2/3 study to evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of the investigational product GNR-055 in MPS II (Hunter syndrome) patients of different age groups.
详细描述
GNR-055 is intended for ERT in patient with Mucopolysaccharidosis type II (MPS II), or Hunter syndrome. MPS II is a recessive X-linked inheritance lysosomal storage disease, which is characterized by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (ID2S), caused by a mutation in the ID2S gene. Enzyme deficiency leads to the accumulation of Glycosaminoglycans (GAG) (mainly of heparan and dermatan sulfates) in lysosomes of almost all types of cells of various tissues and organs. The disease is manifested by growth retardation, damage of many organs and systems, severe deformations of bones and joints, gross facial features, pathology of the respiratory and cardiovascular systems, damage to parenchymal organs (hepatosplenomegaly), and hearing impairment. A severe form of the disease occurs with the involvement of the nervous system in the pathological process, including mental retardation, behavior anomalies, and impaired motor function.
GNR-055 is a recombinant modified ID2S capable to penetrate the blood-brain barrier and thus expected to prevent neurodegenerative consequences and the cognitive deficit and to attain a significant improvement in the life quality and expectancy of patients with MPS II.
Study IDB-MPS-II-III is a multicenter, open-label, multi-cohort study to assess safety, PK and PD, and efficacy of GNR-055 in patients of different age groups with MPS II (Hunter syndrome).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Signed inform consent;
- •Verified diagnosis of MPS II (Hunter syndrome);
- •Naïve patients or patients who have received standard ERT whit idursulfase products;
- •No contraindications for lumbar puncture as judged by the Investigator;
- •Willingness and ability to follow study procedures.
排除标准
- •Clinically pronounced hypersensitivity to ID2S or any other component of the drug product;
- •History of hematopoietic stem cell transplantation (HSCT) or bone marrow transplantation;
- •Implanted or external non-removable metal devices, a cardiac pacemaker, or other objects sensitive to the magnetic field that may pose a danger to both the wearer and the correct operation of magnetic resonance imaging (MRI) equipment;
- •Concomitant diseases and conditions that, in the Investigator's opinion, can put at risk the patient's safety during his/her participation in the study, or which will influence the safety data analysis in case of the disease/condition exacerbation during the study.
研究组 & 干预措施
Adult: GNR-055
GNR-055: 1.0-2.0-3.0 mg/kg
干预措施: GNR-055 1.0-2.0-3.0 mg/kg (Drug)
Paediatric: GNR-055 2.0 mg/kg
GNR-055 2.0 mg/kg
干预措施: GNR-055 2.0 mg/kg (Drug)
Paediatric: GNR-055 3.0 mg/kg
GNR-055 3.0 mg/kg
干预措施: GNR-055 3.0 mg/kg (Drug)
结局指标
主要结局
Incidence of Adverse events (AEs) and Serious Adverse Events (SAEs)
时间窗: Baseline to Week 56
Safety assessment will be performed based on the subjective complaints, physical examination, assessment of vital signs, laboratory tests, and 12-lead ECG; Incidence of allergic and infusion-related reactions; Incidence of Anti-Drug Antibodies (ADAs) against GNR-055 and their neutralizing activity.
Urine GAG excretion
时间窗: Baseline to Week 4, 8, 10, 26, and 52
Changes in levels of urine GAG excretion after multiple-dose administration of GNR-055
次要结局
- Lung Forced Vital Capacity (FVC)(Baseline to Week 8, Week 26, and Week 52)
- Neurocognitive functions assessment(Baseline to Week 12, 26, and 52)
- Serum concentration of the GNR-055(Week 52)
- GAG level in CerebroSpinal Fluid (CSF)(Baseline to Week 6, 10, 26, and 52)
- Serum GAG level(Baseline to Week 4, 8, 10, 26, and 52)
- Large joint range of motion(Week 8, 10, 26, and 52)
- Liver and spleen volumes (MRI)(Baseline to Week 8, 10, 26, and 52)
- 6-minute walk test(Baseline to Week 8, 10, 26, and 52)
- Left ventricular mass by EchoCG(Baseline to Week 8, 10, 26, and 52)
- Brain white/gray matter structures (MRI)(Baseline to Week 26, and 52)
- Serum neuromarkers(Baseline to Week 24, and 52)
- CSF neuromarkers(Baseline to Week 24, and 52)