First in Human Study for the Assessment of Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Multiple Ascending Intravenous Doses of LIS1 in Kidney Transplanted Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Safety of the treatment with LIS1: CRP
研究概览
简要总结
This first in human study aims at evaluating LIS1, a stabilized solution of purified anti-T lymphocytes polyclonal glyco-humanized swine IgG with immunosuppressive activity, in regards of safety, T cell depletion, and pharmacokinetics / pharmacodynamics in 10 kidney transplant recipients.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must be listed for kidney transplantation,
- •AD cohort participants: First transplantation, Panel Reactive Antibody (PRA) < 20%, negative Donor Specific Antibody (DSA), no anti-HLA antibodies, Epstein-Barr Virus positive (EBV+) serology,
- •TD cohort participants: First transplantation, 0-50 % PRA, negative DSA, negative flow cytometry crossmatch (FCXM) for any patients with anti-HLA antibodies on screening is mandatory, Epstein-Barr Virus positive (EBV+) serology
- •Participants must weigh at least 50 kg and have a Body Mass Index (BMI) 18.0 ≤ BMI < 35.0 kg/m2,
- •White Blood Cells > 3000/mm3, platelets > 75000/mm3,
- •Female participants (WOCBP) must have a negative pregnancy test at screening and use a highly effective birth control until 90 days after the last administration of study drug,
- •Non-vasectomized male subjects having a female partner of childbearing potential must agree to the use of a highly effective method of contraception until 90 days after the last administration of study drug,
- •Participants must be capable of giving signed informed consent.
排除标准
- •Patients with an active cancer or a history of kidney cancer,
- •Patients who have previously been exposed to other anti-lymphocyte globulins,
- •Patients with previous organ transplantation,
- •Patients with a history of specific viral infection that would contraindicate depleting antibody therapy (Hepatitis B and C, HIV),
- •Patients with a positive HIV and/or Hepatitis B and C tests
- •Patients who have uncontrolled concomitant bacterial or viral infections (unresolved during screening), mycosis and/or parasitosis,
- •Patients with a significant liver function impairment: enzyme (AST and/or ALT) values must not exceed 1.5 times upper limit of normal,
- •Patients with positive testing for tuberculosis (using QuantiFERON-TB test), Patients with CMV D+/R- constellation at transplant,
- •Patients with seronegative EBV prior to transplantation,
- •Patients who have previously been exposed to antibodies of swine origin,
- •Expanded Criteria Donor (ECD) defined as donor older than 60 years,
- •Participants who have participated in another research study involving an investigational product in the previous 3 months,
- •Patients with cardiovascular or severe respiratory comorbidities (severe chronic respiratory failure, severe pulmonary fibrosis, obesity-ventilation syndrome, severe idiopathic pulmonary arterial hypertension) not allowing general anesthesia,
- •Patients with type 1 diabetes,
- •Participants who are pregnant, breast feeding or planning pregnancy during the study,
- •Participants who have any form of substance abuse (drug, alcohol...), any other health abnormalities (psychiatric disorders) or condition that according to the investigator's opinion might endanger patient during his/her participation in the study.
结局指标
主要结局
Safety of the treatment with LIS1: CRP
时间窗: up to 3 months after the transplant
Laboratory parameters (1): C-Reactive Protein (CRP, mg/L).
Pharmacodynamics (depletion of T lymphocytes) of LIS1
时间窗: up to 3 months after the transplant
Absolute T lymphocyte counts (10\^9/L).
Safety of the treatment with LIS1: Graft rejection
时间窗: up to 3 months after the transplant
Clinical safety parameters (4): Graft rejection (yes/no).
Safety of the treatment with LIS1: Re-admission
时间窗: up to 3 months after the transplant
Clinical safety parameters (6): Re-admission after patient discharge (yes/no).
Safety of the treatment with LIS1: Infection
时间窗: up to 3 months after the transplant
Clinical safety parameters (5): Viral infections (namely Cytomegalovirus \[CMV\], BK virus) (yes/no).
Safety of the treatment with LIS1: Hospitalization
时间窗: up to 3 months after the transplant
Clinical safety parameters (7): Prolonged stay in hospital for \>4 weeks (days).
Safety of the treatment with LIS1: aPTT
时间窗: up to 3 months after the transplant
Laboratory parameters (3): activated Partial Thromboplastin Time (aPTT, seconds).
Safety of the treatment with LIS1: Body temperature
时间窗: up to 3 months after the transplant
Clinical safety parameters (3): Body temperature (Celsius degrees).
Safety of the treatment with LIS1: Complete Blood Count (CBC)
时间窗: up to 3 months after the transplant
Laboratory parameters (4): Platelets (10\^9/L), white blood cells (10\^9/L), absolute neutrophil count (10\^9/L), absolute lymphocyte count (10\^9/L), absolute monocyte count (10\^9/L), absolute eosinophil count (10\^9/L), absolute basophil count (10\^9/L).
Safety of the treatment with LIS1: Blood pressure
时间窗: up to 3 months after the transplant
Clinical safety parameters (1): Systolic and diastolic blood pressure (mm Hg).
Safety of the treatment with LIS1: Pulse rate
时间窗: up to 3 months after the transplant
Clinical safety parameters (2): Pulse rate (beats per minute \[bpm\]) .
Safety of the treatment with LIS1: LDH
时间窗: up to 3 months after the transplant
Laboratory parameters (2): Lactate Dehydrogenase (LDH, µkat/L).
次要结局
- Biology of LIS1 (1): electrolytes plasma concentration(up to 3 months after the transplant)
- Pharmacodynamics of LIS1 (2): cytokines(up to 3 months after the transplant)
- Biology of LIS1 (3): total plasma proteins(up to 3 months after the transplant)
- Immunogenicity of LIS1(up to 3 months after the transplant)
- Pharmacokinetics of LIS1 (1): swine IgG(up to 3 months after the transplant)
- Biology of LIS1 (2): urea and creatinine(up to 3 months after the transplant)
- Biology of LIS1 (4): plasmatic proteins(up to 3 months after the transplant)