A Phase II Pilot Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacodynamics and Pharmacokinetics of IdeS in Asymptomatic Antibody-Mediated Thrombotic Thrombocytopenic Purpura (TTP) Patients With Low ADAMTS13 Activity
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- Safety and Tolerability as Measured by Type, Frequency and Intensity of Adverse Events
研究概览
简要总结
The main purpose of this study is to evaluate safety and tolerability in patients diagnosed with asymptomatic antibody-mediated TTP with low ADAMTS13 activity after receiving single intravenous dose of IdeS.
详细描述
Immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS) is an IgG specific endopeptidase which cleaves IgG molecules and efficiently neutralizes Fc-mediated activities. IdeS-mediated IgG degradation constitutes a novel therapeutic principle for the treatment of IgG-driven human diseases.
In addition to assessing the safety and tolerability of IdeS the study will also assess the efficacy of IdeS to significantly increase the ADAMTS13 activity and decrease the anti-ADAMTS13 antibody levels in patients diagnosed with asymptomatic antibody-mediated TTP with low ADAMTS13 activity.
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
- 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
- •Age 18 years or above
- •Diagnosed with acquired TTP with ADAMTS13 levels of ≤ 10 % in clinical remission and with measurable or previously confirmed ADAMTS13 antibodies
排除标准
- •Prior malignancy within 5 years
- •Test positive for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus (HIV)
- •Ongoing infectious disease including P-CRP >10
- •Test positive for IgE antibodies against IdeS
- •Secondary cause of TTP
- •Rituximab treatment or other antibody-based therapy within 7 days prior to IdeS dosing
- •Treatment with investigational medicinal product within the last 12 weeks proceeding screening
- •Severe other conditions requiring treatment and close monitoring, e.g. cardiac failure > NYHA (New York Heart Association) grade 3, unstable coronary disease or oxygen dependent COPD
- •History of any other clinically significant disease or disorder which may either put the patient at increased risk because of participation in the study, or influence the results or the patient's ability to participate in the study
- •Hypogammaglobulinemia defined as any values of P-total IgG less than 3 g/L
- •History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to IdeS (e. g. streptokinase and/or staphylokinase)
- •Substance abuse or other concurrent medical condition that could confound study interpretation or affect the patient's ability to tolerate or complete the study
- •Breast feeding women or women with a positive pregnancy test
- •Previously received IdeS treatment
研究组 & 干预措施
Treatment IdeS (0.25 mg/kg)
A single 30 minutes i.v. infusion of IdeS (0.25 mg/kg). Following an evaluation of safety and efficacy in 3 patients receiving 0.25 mg/kg there will be a potential to increase the IdeS dose to 0.5 mg/kg for the remaining 3 patients.
干预措施: IdeS (0.25 mg/kg) (Biological)
Treatment IdeS (0.50 mg/kg)
A single 30 minutes i.v. infusion of IdeS (0.50 mg/kg).
干预措施: IdeS (0.50 mg/kg) (Biological)
结局指标
主要结局
Safety and Tolerability as Measured by Type, Frequency and Intensity of Adverse Events
时间窗: From dosing until end of follow up on day 64
Data on AEs were obtained if spontaneously reported by the patient, if reported in response to an open question from the study personnel or if revealed by observation. A treatment emergent AE (TEAE) is defined as any AE occurring after administration of the IMP and within the time of the residual drug effect period (i.e. 30 days after IMP administration). AEs reported in ClinicalTrials.gov include TEAEs and post-treatment AEs, i.e. all AEs occurring after administration of IdeS until end of study. Please refer to Adverse Event section for details on reported AEs
次要结局
- Number of Patients With Change From Baseline in ADAMTS13 Activity(From day of dosing until end of follow up on day 64)
- Number of Patients With Change From Baseline in Pharmacodynamics as Measured by Level of IgG(From day of dosing until end of follow up on day 64)
- Number of Patients for Whom a Decreased ADAMTS13 Activity Returned to Normal Levels at Different Time-points in the Study(From day of dosing until end of follow up on day 64)
- Maximum Serum Concentration (Cmax) of IdeS(From day of dosing until day 14)
- Number of Patients With Change From Baseline in ADAMTS13 Antibody Levels(From day of dosing until end of follow up on day 64)
- Number of Patients Showing IdeS Immunogenicity as Measured by Anti-drug Antibodies(From day of dosing until end of follow up on day 64)
- Time-point for Maximum Serum Concentration of IdeS(From day of dosing until day 14)
- Number of Patients With Change From Baseline in Pharmacodynamics as Measured by Level of F(ab')2 Fragments(From day of dosing until end of follow up on day 64)