A Double-Blind, Placebo-Controlled, Multicenter, Randomized Phase 2 Trial Evaluating the Efficacy and Safety of Felzartamab in Recipients of Kidney Transplants With Late Isolated Microvascular Inflammation (MVI)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Biogen
- 入组人数
- 81
- 试验地点
- 44
- 主要终点
- Part A: Percentage of Participants Who Achieve Biopsy-proven Histologic Resolution (BPHR)
研究概览
简要总结
In this study, researchers will learn more about a drug called felzartamab in people who have received a kidney transplant and later developed a condition called microvascular inflammation (MVI). MVI is a type of injury to small blood vessels in the transplanted kidney and may be a sign of rejection by the body. It can lead to serious kidney problems over time.
In many cases, MVI is caused by antibodies that attack the transplanted kidney. But in some people, MVI happens without these antibodies. This type of MVI is called isolated MVI. There are currently no approved treatments for isolated MVI.
The main goal of the study is to learn about the effect felzartamab has on inflammation in the transplanted kidney. The main question researchers want to answer is:
• How many participants have no signs of active inflammation in the transplanted kidney after 24 weeks of treatment with felzartamab?
Researchers will also study how felzartamab affects kidney function, immune activity, and overall health. They will monitor safety through kidney biopsies, lab tests, and by recording adverse events throughout the study.
Adverse events are health problems that may or may not be caused by the study drug.
The study will be done in 2 parts as follows:
- Participants will be randomly assigned to receive either felzartamab or a placebo. A placebo looks like the study drug but contains no real medicine.
- In Part A, participants will receive their assigned drug for 24 weeks. Neither the researchers nor the participants will know who is receiving felzartamab or placebo.
- Part B will last another 28 weeks. All participants will receive felzartamab and both participants and researchers will know this.
- All treatments will be given by intravenous (IV) infusion at the study site.
- Participants will have kidney biopsies at the start of the study, at Week 24, and at Week 52 to help measure changes in inflammation.
- Participants will stay in the study for about 1 year.
详细描述
The primary objective of the study is to evaluate the efficacy of felzartamab compared to placebo in kidney transplant recipients in Cohort 1 (Part A). The secondary objectives of the study are to evaluate the efficacy of felzartamab compared to placebo through additional clinical endpoints (Part A), summarize efficacy of felzartamab up to Week 52 in kidney transplant recipients in Cohorts 1 and 2 (Part B); evaluate safety of felzartamab in kidney transplant recipients in Cohorts 1 and 2 (Parts A and B) and to assess the pharmacokinetic (PK) profile and immunogenicity of felzartamab (Parts A and B).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a 2-part trial: Part A will be randomized and placebo-controlled, and Part B will be open-label.
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •MVI (MVI ≥2), donor specific antibody (DSA)-negative that is either complement activation (C4d) negative or C4d positive (biopsy-confirmed) without T cell-mediated rejection (TCMR) per central reading, as defined by the Banff 2022 criteria.
- •Biopsy must be within 3 months (preferably within 1 month) prior to randomization and meet adequate criteria (option a preferred over option b):
- •Adequate: 10 or more non-sclerotic/evaluable glomeruli and two muscular arteries
- •Minimally Adequate: at least 7 non-sclerotic/evaluable glomeruli and one muscular artery
- •For participants who received any prior treatment for antibody-mediated rejection (AMR), MVI, or TCMR as outlined in Exclusion Criterion 5, the biopsy must be performed at least 6 weeks after completing (or stopping) prior treatment.
- •Kidney transplant at least 6 months prior to Screening visit (recipients of either living or deceased donors).
- •DSA: Human leukocyte antigen (HLA) Class I and II antigen-specific DSA-negative (preformed and de novo DSA) as determined by the local laboratory's definition of positivity using single-antigen bead-based assays within 3 months prior to randomization.
排除标准
- •Transplant: Blood type (ABO)-incompatible transplant.
- •History of multiple organ transplants including en bloc and dual kidney transplants.
- •Presence of HLA donor-specific antibodies.
- •Acute, rapid decline in renal function, defined as a participant likely to require renal replacement therapy within the next 30 days as determined by the Investigator.
- •Prior AMR or TCMR treatment (with the exception of corticosteroids) within 3 months prior to randomization is excluded as listed below. Participants who received any of these treatments between 3 and 6 months prior to randomization must have both a renal biopsy (IC3) and DSA testing at least 6 weeks after completing (or stopping) treatment in order to confirm continuing MVI≥2 and DSA negative status and to determine eligibility:
- •Intravenous or subcutaneous immunoglobulin (IVIg or subcutaneous immunoglobulin [SCIg]) or plasma exchange (PLEX).
- •Complement system inhibitors (e.g., eculizumab).
- •Proteasome inhibitors (e.g., bortezomib).
- •The anti-interleukin-6 receptor (anti-IL-6R) tocilizumab.
- •Any B cell-depleting therapy (including anti-CD20 agents [e.g., rituximab]) within 3 months prior to randomization.
- •Any other investigational agent within 3 months or 5 half-lives (whichever is longer) of randomization.
- •Note: Other protocol-defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Felzartamab
Participants will receive multiple IV doses of felzartamab.
干预措施: Felzartamab (Drug)
Placebo and Felzartamab
Participants will receive multiple IV doses of placebo followed by multiple doses of IV felzartamab.
干预措施: Placebo (Drug)
Placebo and Felzartamab
Participants will receive multiple IV doses of placebo followed by multiple doses of IV felzartamab.
干预措施: Felzartamab (Drug)
结局指标
主要结局
Part A: Percentage of Participants Who Achieve Biopsy-proven Histologic Resolution (BPHR)
时间窗: Week 24
次要结局
- Part A: Percentage of Participants in Cohort 2 Who Achieve BPHR(Week 24)
- Part A: Percentage of Participants Who Achieve an MVI Score of 0(Week 24)
- Part A: Microvascular Inflammation (MVI) Score(Week 24)
- Part A: Change from Baseline in Estimated Glomerular Filtration Rate (eGFR)(Baseline, Week 24)
- Part A: Percentage of Participants in the Complement Activation (C4d) Positive Cohort who Achieve BPHR(Week 24)
- Part B: Percentage of Participants Who Achieve BPHR(Weeks 24 and 52)
- Part B: MVI Score(Weeks 24 and 52)
- Part B: Percentage of Participants Who Achieve an MVI Score of 0(Weeks 24 and 52)
- Part B: Change from Baseline in eGFR(Baseline, Weeks 24 and 52)
- Part B: Time to All-cause Allograft Loss(Up to Week 52)
- Parts A and B: Number of Participants with Adverse Events (AEs)(From first dose of study drug up to end of study follow-up (up to week 57))
- Parts A and B: Percentage of Participants with T Cell-mediated Rejection (TCMR) by Biopsy(Weeks 24 and 52)
- Parts A and B: Number of Participants with Clinically Significant Laboratory Abnormalities(From time of first dose to end of trial visit (Up to Week 52))
- Parts A and B: Number of Participants with Clinically Significant Vital Signs Abnormalities(From time of first dose to end of trial visit (Up to Week 52))
- Parts A and B: Number of Participants with Clinically Significant Electrocardiogram (ECG) Abnormalities(From time of first dose to end of trial visit (Up to Week 52))
- Parts A and B: Felzartamab Serum Concentration(Up to Week 52)
- Parts A and B: Number of Participants with Anti-drug Antibodies (ADAs) Against Felzartamab(Baseline, up to Week 52)