A Phase 2a Single-arm, Prospective, Open-label Pilot Study to Evaluate the Safety and Efficacy of Dual Costimulation Blockade With VIB4920 and Belatacept for Prophylaxis of Allograft Rejection in Adults Receiving a Kidney Transplant
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 25
- 试验地点
- 4
- 主要终点
- Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR) of Grade 1A or Higher, Graft Loss or Death at Week 24
研究概览
简要总结
The purpose of this study is to evaluate the efficacy, safety and tolerability of dual costimulation blockade with VIB4920 in combination of belatacept in adult male or female recipients of a renal allograft from a deceased, living unrelated or human leukocyte antigen (HLA) non-identical living related donor.
详细描述
Study with completed results acquired from Horizon in 2024.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 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
- •Recipients of a first renal transplant from standard criteria deceased, living unrelated or HLA non-identical living related donor.
- •Recipients who are at low immunologic risk:
- •No donor specific antibodies (DSA), and
- •Negative cross-match testing.
- •Recipients with up to date vaccination as per local immunization schedules.
- •Male and female participants who agree to follow protocol defined contraceptive methods.
排除标准
- •Participants receiving an allograft from an ABO-incompatible donor.
- •Participants treated with systemic immunosuppressive drug therapy for more than a total of 2 weeks within 24 weeks prior to informed consent form signature.
- •Participants who have undergone lymphodepleting therapy.
- •Participants with medical history of confirmed venous thromboembolism, arterial thrombosis, coagulopathy or known platelet disorders.
- •Participants with risk factors for venous thromboembolism or arterial thrombosis, prothrombotic status.
- •Participants requiring treatment with antithrombotic drugs (clopidogrel, prasugrel, warfarin, others).
- •Participants requiring long-term systemic anticoagulation after transplantation, which would interfere with obtaining biopsies.
- •Participants with any contraindication to kidney biopsy.
- •Cytomegalovirus (CMV)-seronegative recipients of a CMV-seropositive donor kidney, or unknown CMV serostatus.
- •Epstein-Barr virus (EBV)-seronegative or with unknown EBV serostatus.
- •Receipt of live (attenuated) vaccine within the 4 weeks before screening.
- •Participants with high potential of graft loss due to recurrence of underlying kidney disease.
- •Prior solid organ transplant or potential to require a concurrent organ or cell transplant.
- •Previous treatment with belatacept and cluster of differentiation 40 (CD40) or anti-CD40L agents.
- •Use of B cell depleting therapy, non-depleting B cell directed therapy e.g., belimumab or abatacept within 1 year prior to enrolment.
- •At screening blood tests any of the following:
- •Aspartate aminotransferase (AST) > 2.5 × upper limit of normal (ULN)
- •Alanine aminotransferase (ALT) > 2.5 × ULN
- •Alkaline phosphatase (ALP) > 2.5 × ULN
- •Total bilirubin (TBL) > 2 × ULN
- •Hemoglobin < 75 g/L
- •Neutrophils < 1.5 × 10^9/L
- •Platelets < 100 × 10^9/L
- •Participants with severe systemic infections, current or within the 2 weeks prior to transplant surgery.
- •Positive test for chronic hepatitis B infection at screening or within the last 12 months.
- •Positive test for hepatitis C virus antibody at screening or within the last 12 months.
- •Positive test for human immunodeficiency viruses antibody at screening or within the last 12 months.
- •History of or active tuberculosis (TB), or a positive QuantiFERON®-TB Gold test at screening, unless previously treated for latent tuberculosis.
- •History of cancer, except as follows:
- •In situ carcinoma of the cervix treated with apparent success with curative therapy > 12 months prior to screening; or
- •Cutaneous basal cell or squamous cell carcinoma treated with apparent success with curative therapy.
- •Lactating or pregnant females.
研究组 & 干预措施
Belatacept+VIB4920
Participants will be admitted to the transplant center for the administration of VIB4920 and belatacept (with Thymoglobulin and corticosteroids) and will be discharged on Day 3/4 at the discretion of the investigator. Participants will return to the study center to receive study drugs (VIB4920 and /or belatacept) weekly for 2 visits, then every 2 weeks for 5 visits, and then monthly for 9 visits for safety monitoring.
干预措施: Belatacept (Drug)
Belatacept+VIB4920
Participants will be admitted to the transplant center for the administration of VIB4920 and belatacept (with Thymoglobulin and corticosteroids) and will be discharged on Day 3/4 at the discretion of the investigator. Participants will return to the study center to receive study drugs (VIB4920 and /or belatacept) weekly for 2 visits, then every 2 weeks for 5 visits, and then monthly for 9 visits for safety monitoring.
干预措施: VIB4920 (Drug)
Belatacept+VIB4920
Participants will be admitted to the transplant center for the administration of VIB4920 and belatacept (with Thymoglobulin and corticosteroids) and will be discharged on Day 3/4 at the discretion of the investigator. Participants will return to the study center to receive study drugs (VIB4920 and /or belatacept) weekly for 2 visits, then every 2 weeks for 5 visits, and then monthly for 9 visits for safety monitoring.
干预措施: Thymoglobulin (Drug)
Belatacept+VIB4920
Participants will be admitted to the transplant center for the administration of VIB4920 and belatacept (with Thymoglobulin and corticosteroids) and will be discharged on Day 3/4 at the discretion of the investigator. Participants will return to the study center to receive study drugs (VIB4920 and /or belatacept) weekly for 2 visits, then every 2 weeks for 5 visits, and then monthly for 9 visits for safety monitoring.
干预措施: Methylprednisolone (Drug)
结局指标
主要结局
Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR) of Grade 1A or Higher, Graft Loss or Death at Week 24
时间窗: Week 24
Histological grading of acute allograft rejection from biopsy specimens was based on Banff criteria 2017. Grade IA: Moderate tubulitis and at least moderate total cortical inflammation and at least moderate scarred cortical inflammation and other known causes ruled out. Grade IB: Severe tubulitis and at least moderate total cortical inflammation and at least moderate scarred cortical inflammation and other known causes ruled out. Grade II. Arterial intimal fibrosis with mononuclear cell inflammation, formation of neointima.
次要结局
- Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR) of Grade 1A or Higher, Graft Loss or Death at Weeks 12 and 48(Weeks 12 and 48)
- Percentage of Participants With Antibody-Mediated Rejection(Week 12, 24, 48)
- Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR)(Week 12, 24, 48)
- Percentage of Participants With De Novo Donor-specific Antibodies (dnDSA)(Week 12, 24, 48)
- Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR), Graft Loss, Death or Loss to Follow-up (LTFU)(Week 12, 24, 48)
- Percentage of Participants With Biopsy Proven Acute Rejection (BPAR)(Week 12, 24, 48)
- Percentage of Participants With Treated Acute Rejections(Week 12, 24, 48)