A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Evaluate Efficacy and Safety of ALXN2030 in Adult Patients With Antibody-Mediated Rejection After Kidney Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 47
- 试验地点
- 107
- 主要终点
- Biopsy-proven histologic resolution
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy of ALXN2030 compared with placebo on biopsy proven histologic resolution in participants with active or chronic active antibody-mediated rejection (AMR) at Week 52.
详细描述
This prospective trial will assess the efficacy, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of ALXN2030 in kidney transplant recipients with active or chronic active AMR. The study is designed as a randomized, controlled, double-blind phase 2 trial. Participants will be randomized in a 1:1:1 ratio to receive either ALXN2030 Dose A, ALXN2030 Dose B, or placebo for a double-blind treatment period of 52 weeks. All arms will receive standard of care immunosuppressive treatment. During the treatment period, study participants will be subjected to repeated allograft biopsies at 28 and 52 weeks. At the end of the double-blind treatment period, participants may continue into the Open-Label Extension (OLE) Treatment Period (52 weeks). Participants randomized to placebo will be re-randomized 1:1 to ALXN2030 Dose A or ALXN2030 Dose B. Safety Follow-Up will start after the end of Treatment (Week 104) until week 48 after the last dose.
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)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Kidney transplant received ≥ 6 months
- •Active or chronic active AMR according to Banff 2022 classification, based on Screening kidney biopsy
- •Either positive C4d on Screening kidney biopsy based on the Central Pathology Laboratory report and/or positive HLA Class I and/or II antigen-specific DSA as determined by the local laboratory's definition of positivity using single-antigen bead based assays
- •MVI score ≥ 2 (g ≥ 1 and ptc ≥ 1)
- •eGFR ≥ 30 mL/min/1.73 m2
- •Must be vaccinated against meningococcal infection from serogroups A, C, W, Y (and B where available) at least 14 days prior to but no more than 3 years prior to Day 1
- •Must be vaccinated for S pneumoniae prior to randomization
- •Must be vaccinated for H influenzae type B (where available) prior to randomization
- •Body weight ≥ 50 kg at Screening
排除标准
- •Biopsy-based diagnosis of any of the following at Screening:
- •TCMR, according to the Banff grade ≥ 1
- •Polyoma virus nephropathy
- •Severe thrombotic microangiopathy
- •Glomerulonephritis
- •ABO-incompatible transplant
- •uACR > 2200 mg/g
- •Multiorgan transplant recipient (except for previous multiple kidney transplants) or cell transplant (islet, bone marrow, stem cell) recipient
- •Planned or recent treatments, < 90 days prior to the Screening Visit and during Screening, for Acute Rejection, AMR (including plasmapheresis, plasma exchange, IVIg, B-cell depleting therapy, IL inhibitors, proteasome inhibitors, high-dose corticosteroids [except for tapering]), HDS products with known hepatotoxic ingredients, TCMR (including T-cell depleting therapy), excluding the SoC immunosuppressant treatment which will be allowed and should be stable during the entire treatment.
- •Known medical or psychological condition, including substance abuse or use disorder (including alcohol), or risk factor that may interfere with study participation, pose additional risk, or confound study outcomes
研究组 & 干预措施
Placebo
Placebo will be administered during the Double-Blind Treatment Period of 52 weeks.
干预措施: Placebo (Drug)
ALXN2030 Dose A
During the Double-Blind Treatment Period, participants will receive ALXN2030 dose A over 52 weeks. At Week 52, participants may continue into the Open Label Extension (OLE).
干预措施: ALXN2030 (Drug)
ALXN2030 Dose B
During the Double-Blind Treatment Period, participants will receive ALXN2030 dose B over 52 weeks. At Week 52, participants may continue into the OLE Period.
干预措施: ALXN2030 (Drug)
结局指标
主要结局
Biopsy-proven histologic resolution
时间窗: Week 52
次要结局
- Biopsy-proven histologic resolution(Week 28)
- Change From Baseline in biopsy-proven histologic scores(Baseline, Weeks 28 and 52)
- Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52(Baseline up to week 52)
- Annualized Total eGFR Slope(Baseline up to Week 52)
- Stabilized eGFR(Baseline up to Week 52)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs)(Day 1 up to Week 104)
- Number of Participants With Anti-drug Antibodies (ADAs)(Day 1 through Week 104)
- Plasma Concentration of ALXN2030(Baseline up to Week 104)
- Plasma Concentration of C3 Protein(Baseline up to Week 104)
- Change From Baseline in Serum Complement Functional Activity(Baseline, up to Week 52 and up to Week 104)