Phase II, Open Label Adaptive Design Dose Finding Study to Investigate Effect of Synthetic PreImplantation Factor (sPIF) in Patients With High Panel Reactive Antibodies
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Evaluate the safety and tolerability of multiple ascending, subcutaneously administered doses of sPIF in patients with high panel reactive antibodies (PRA) with no SAEs greater than grade 3
研究概览
简要总结
This is an open labeled dose finding adaptive design study. Patients with elevated cPRA values, 30-60% will be recruited and administered sPIF injected subcutaneously for 14 doses; one dose on Monday, Wednesday, Friday, or Tuesday, Thursday, Saturday, per individual patient dialysis schedule.
详细描述
The purpose of this study is to determine the sPIF dose that reduces serum cPRA to <30%, when administered 14 doses. Safety, tolerability, and efficacy will be evaluated at day 42 and and day 84. The suitability of a patient to receive a kidney transplant will also be monitored up to 6 months after Day 84. Safety and tolerability will be assessed at each of the increased doses and throughout the treatment duration. Exploratory analysis of blood indices will be carried out and changes based on history, physical and laboratory exams will be assessed according to the 12 systems.
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
- •Outpatient male and females 18-75 years old
- •Able and willing to give written informed consent and comply with the requirements of the study protocol
- •Calculated panel reactive antibody (cPRA) >30% and <60% with a threshold using mean fluorescent intensity (MFI) of 3,000 or standard fluorescence intensity (SFI) of 60,000 over six months.
- •Women who are of childbearing potential must have a negative serum pregnancy test prior to being enrolled in the study and agree to use effective method of contraception throughout the 84-day study.
- •Patients on kidney dialysis 3.3 Exclusion Criteria
- •Patients not capable of following through the treatment for various reasons as determined by treating physicians
- •Pregnant females
- •Requiring blood transfusions
- •Have an active infection
- •Infection with hepatitis C virus (HCV) or hepatitis B virus(HBV) or human immunodeficiency virus (HIV), lack of documentation of treatment of a positive PPD, baseline leukopenia, white blood cell count (WBC) <4.0, thrombocytopenia (platelet count <100,000/mm) or difficult to treat anemia, a hematocrit chronically <25% on intravenous iron and EPO (erythropoietin) therapy
- •Active cancer within 5 years
- •Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
排除标准
- 未提供
研究组 & 干预措施
synthetic preImplantation factor 1 mg/kg
Patients will be dosed SQ with 14 doses of sPIF
干预措施: synthetic PreImplantation Factor (Drug)
synthetic preImplantation factor 2 mg/kg
Patients will be dosed SQ with 14 doses of sPIF
干预措施: synthetic PreImplantation Factor (Drug)
synthetic preImplantation factor 3 mg/kg
Patients will be dosed SQ 14 doses
干预措施: synthetic PreImplantation Factor (Drug)
synthetic preImplantation factor 4 mg/kg
Patients will be dosed SQ with 14 doses of sPIF
干预措施: synthetic PreImplantation Factor (Drug)
synthetic preImplantation factor 5 mg/kg
Patients will be dosed SQ with 14 doses of sPIF
干预措施: synthetic PreImplantation Factor (Drug)
结局指标
主要结局
Evaluate the safety and tolerability of multiple ascending, subcutaneously administered doses of sPIF in patients with high panel reactive antibodies (PRA) with no SAEs greater than grade 3
时间窗: 84 days
No grade SAE \> Grade 3
Evaluate the pharmacokinetics of sPIF levels in the circulation after multiple ascending, subcutaneously administered doses of sPIF by measurement of sPIF in circulation
时间窗: 84 days
sPIF circulating levels are assessed following dialysis and post-first injection at 1, 2, and 4 hours and before last sPIF dose, trough values.
Evaluate the effect of sPIF on serum cPRA following administration of multiple ascending, subcutaneously administered doses as determined by CPRA levels
时间窗: 84 days
Determine cPRA levels
次要结局
- Assess number of patients receiving a kidney transplant within 6 months post-day 84 as dertermined by patients being available for kidney transplant(6 months post study drug treatment)
- Determine the percentage of patients in remission ass determined by CPRA less than 30%(84 days)
研究者
Christopher O'Brien, MD
Professor
University of Miami