NCT03781414终止2 期
A 12-month, Open-label, Multicenter, Randomized, Safety, Efficacy, Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of Two Regimens of Anti-CD40 Monoclonal Antibody, CFZ533 vs. Standard of Care Control, in Adult de Novo Liver Transplant Recipients With a 12-month Additionalr Follow-up and a Long-term Extension (CONTRAIL I)
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 129
- 试验地点
- 10
- 主要终点
- Percentage of Patients With Composite Event (Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death) Over 12 Months
研究概览
简要总结
This was a multicenter, open-label, active-controlled study to evaluate the efficacy, safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of two CFZ533 maintenance doses in de novo liver transplant recipients.
详细描述
The study was designed as a randomized, 36-month clinical trial comprised of:
- A screening period (up to 2 months) starting from informed consent, screening visit, and including successful liver transplantation (LTx).
- A run-in treatment period following successful transplantation that ended on the day of randomization or randomization failure, at Day 8 (with visit window of +/- 2 days) post-LTx.
- The primary treatment period (Treatment Period 1) starting at randomization Day 8 +/- 2 post-LTx up to Month 12 followed by a 12-month follow-up treatment period (Treatment Period 2) until Month 24.
- The long-term extension period (Treatment Period 3) starting post Month 24 until the end of the study (EOS).
- A minimum 12-week safety follow-up period for all patients after EOS.
The study was terminated following less favorable efficacy by Iscalimab (CFZ533) in liver transplant patients compared to tacrolimus.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Screening period up to liver transplantation:
- •Written informed consent obtained before any assessment.
- •Male or female patients between 18 to 70 years of age.
- •Recipients of a primary liver transplant from a deceased donor.
- •Up to date vaccination as per local immunization schedules.
- •Recipients tested negative for HIV.
- •MELD score ≤
- •Transplantation to occur within defined screening period following informed consent signature.
- •At randomization (Day 8 +/- 2):
- •Recipients with no active HCV and HBV replication.
- •Allograft is functioning at an acceptable level by the time of randomization as defined by AST, ALT and Alkaline Phosphatase levels ≤ 5 times ULN and Total Bilirubin ≤ 2 times ULN.
- •Renal function (eGFR, MDRD-4 formula) ≥ 30 mL/min/1.73 m2 based on most recent post-transplant value prior to randomization.
- •Recipients who have been initiated on an immunosuppressive regimen that contains TAC, mycophenolate mofetil (MMF) and corticosteroids (CS) as per protocol.
排除标准
- •Screening period up to liver transplantation:
- •Use of other investigational drugs at screening within 30 days or 5 half-lives of screening.
- •Recipients of multiple solid organ or islet cell transplants, or recipients that have previously received a tissue transplant, or a combined liver-kidney transplant.
- •Recipients of a liver from a donor after cardiac death (DCD), from a living donor, or of a split liver.
- •Recipient who tested negative for Epstein Barr virus (EBV) within 28 days prior to baseline visit.
- •Recipients receiving an ABO incompatible allograft.
- •History of malignancy of any organ system (except hepatocellular carcinoma (HCC) or localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there was evidence of local recurrence or metastases.
- •Hepatocellular carcinoma that did not fulfill Milan criteria (1 nodule ≤ 5 cm, 2-3 nodules all ≤ 3 cm, without evidence of metastatic disease or vascular invasion) at the time of transplantation.
- •Recipients transplanted for acute liver failure (does not apply to acute on chronic liver failure).
- •Any use of antibody induction therapy, or use of any immunosuppressive medications (or other medications prohibited by the protocol).
- •Patients who have received a live vaccine within four weeks prior to transplantation.
- •Recipients with HIV positive donor.
- •Recipients with donors HBsAg positive.
- •Recipients who were HCV antibody-positive without documented sustained viral response (SVR) at 12 weeks after finishing anti HCV treatment (e.g., direct-acting antivirals).
- •Recipients with HCV RNA-positive donors.
- •Recipients with donors with macrovesicular steatosis > 30%.
- •Pregnant or nursing (lactating) women.
- •At randomization (Day 8 +/- 2):
- •Any post-transplant history of thrombosis, occlusion or stent placement in any hepatic arteries, hepatic veins, portal vein or inferior vena cava at any time during the run-in period prior to randomization. Absence of any graft vascular thrombosis or occlusion (by diagnostic method used at the site to assess vascular patency) must be confirmed by imaging prior to randomization.
- •Recipients with platelet count < 50,000/mm
- •Recipients with an absolute neutrophil count of < 1,000/mm³ or white blood cell count of < 2,000/mm³.
- •Recipients with clinically significant systemic infection requiring use of intravenous (IV) antibiotics.
- •Evidence of active tuberculosis (TB) infection.
- •Recipients who are in a critical care setting at the time of randomization requiring life support measures such as mechanical ventilation, dialysis, requirement of vasopressor agents.
- •Recipients who were on renal replacement therapy at randomization.
- •Any episode of acute rejection or suspected rejection prior to randomization.
- •HCC patients whose explanted liver graft pathology report shows (i) pathologic Tumor-Node-Metastasis (pTNM) stage beyond T2N0M0, (ii) presence of mixed carcinoma, (iii) microvascular invasion despite pTNM stage.
- •Patients with body weight < 30 kg or > 180 kg.
研究组 & 干预措施
TAC Control
Active Comparator
Tacrolimus (TAC) + Mycophenolate mofetil (MMF) + Corticosteroids (CS) up to End of Study (EOS). Initial TAC target trough were between 5-15 ng/mL during the run-in period. From randomization onwards, the TAC levels were adjusted as per local label.
干预措施: Tacrolimus - MMF - corticosteroids (Drug)
CFZ533 600 mg regimen
Experimental
Loading doses of 30 mg/kg IV on Day 8 (with +/- 2 days window), and 15 mg/kg IV on Day 15. The subcutaneous (SC) administration of 600 mg (2 injections of 2 mL CFZ533 at 150 mg/mL) every 2 weeks started on Day 29, in combination with MMF and CS up to EOS.
干预措施: CFZ533 (Biological)
CFZ533 300 mg regimen
Experimental
Single loading dose of 30 mg/kg IV on Day 8 (with +/- 2 days window). The SC administration of 300 mg (1 injection of 2 mL CFZ533 at 150 mg/mL) every 2 weeks started on Day 29, in combination with MMF and CS up to EOS.
干预措施: CFZ533 (Biological)
结局指标
主要结局
Percentage of Patients With Composite Event (Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death) Over 12 Months
时间窗: Baseline to Month 12
The occurrence of biopsy proven acute rejection (BPAR) was evaluated based on central pathologist evaluation. Graft loss and death was evaluated as per local evaluation.
次要结局
- Percentage of Patients With Dose Interruptions and Permanent Discontinuation of Study Treatment(Baseline to Month 24)
- Mean Change in Estimated Glomerular Filtration Rate (eGFR) From Randomization to Month 12(Baseline to Month 12)
- Number of Participants With Treatment Emergent Adverse Events(Baseline up to 14 weeks after last dose of study medication (CFZ533 participants) and until 12 weeks for TAC participants, up to approx. 184 weeks.)
研究者
研究点 (10)
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