A Randomized, Controlled, Open Label, Two Arms, Exploratory Study to Evaluate the Effect of Everolimus on Histologically Assessed Fibrosis Progression (Ishak-Knodell) in Liver Transplant Recipients With Recurrent Hepatitis C Viral Infection as Compared to Standard Treatment.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Change From Baseline in Fibrosis Staging Score (Measured by the Ishak-Knodell Staging Score) Between Baseline and 24 Months Post-transplant.
研究概览
简要总结
This study will assess the efficacy of everolimus as an inhibitor of fibrosis progression in liver transplant patients who have a recurrence of hepatitis C viral infection in the transplant
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
- 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
- •Male or female patients 18 - 65 years of age
- •Recipients of deceased or living donors
- •Patients who had undergone primary liver transplantation at least 6 months before enrolment
- •Recurrent Hepatitis C viral infection and histologically confirmed liver fibrosis (stage I-IV in the Ishak-Knodell scale) obtained at baseline or within the previous 6 months to the date of enrolment
- •Patients receiving tacrolimus or cyclosporine micro-emulsion with or without - Mycophenolic acid (MPA), with or without steroids.
- •Absence of acute rejection episodes within the previous 6 months to the date of enrolment
- •Patient in whom an allograft biopsy will not be contraindicated
- •Patient willing and capable of giving written informed consent for study participation and able to participate in the study for 24 months
- •Patients with Hepatocellular carcinoma (HCC) within the University California, San Francisco (UCSF) Criteria and no recurrence for at least 18 months after OLT.
排除标准
- •Recipients of multiple organ transplants or patients who have undergone retransplantation
- •Current biliary complications
- •History of drug or alcohol abuse within 1 year before enrolment
- •Patients treated with anti-hepatitis C virus treatment at the time of enrollment or within the previous month to the date of enrolment
- •Co-infection with Hepatitis B virus (HBV) or Human Immunodeficiency Virus (HIV)
- •Patients with Leukocyte count (WBC) < 3000/mm3, platelet count < 75000/mm3 or Hemoglobin (Hb) < 8 g/dl
- •Patients with proteinuria >1g/24 hours
- •Patient with a current severe systemic infection
- •Other protocol defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
CsA-TAC
Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor [CNI] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)[MPA], with or without steroids) / no everolimus introduction.
干预措施: CsA-TAC (standard Treatment) (Drug)
everolimus
Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
干预措施: Everolimus (Drug)
结局指标
主要结局
Change From Baseline in Fibrosis Staging Score (Measured by the Ishak-Knodell Staging Score) Between Baseline and 24 Months Post-transplant.
时间窗: baseline, 24 Months
Ishak-Knodell Score: 0=No fibrosis; 01=Fibrous expansion of some portal areas, with or without short fibrous septa; 02=Fibrous expansion of most portal areas, with or without short fibrous septa; 03=Fibrous expansion of most portal areas, with occasional portal to portal (P-P) bridging; 04=Fibrous expansion of portal areas, with marked bridging (portal to portal (P-P) as well as portal to central (P-C)); 05=Marked bridging (P-P and/or P-C) with occasional nodules (incomplete cirrhosis); 06=Cirrhosis, probable or definite Decrease in score from baseline indicates improvement
次要结局
- Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization(Baseline, 12 months, 24 months)
- Percentage of Patients With Death, Graft Loss and Biopsy Proven Acute Rejection (BPAR) Between Study Groups(24 Months)
- Number of Patients With Events (Progression to Cirrhosis, Retransplantation, HCV Related Death, First BPAR, Graft Loss)at 12 and 24 Months(12 months, 24 months)
- Comparison of Renal Function (Glomerular Filtration Rate [GFR] Calculated Using the Modification of Diet in Renal Disease Study Group [MDRD] Formula) Between Study Groups(12 months, 24 months/EOS)
- Comparison of the Effect of Both Regimens in the Necroinflammatory Grading Score (Ishak-Knodell) (Portal Inflammation)(baseline, 12 months, 24 months)
- Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry(baseline, 12 and 24 months)
- Percentage of Patients in Each Study Arm With Increase of ≥1 Point in the Ishak-Knodell Staging Score in Fibrosis(baseline to month 24)
- Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization(baseline, 12 months, 24 months/EOS)