2024-510615-29-00招募中3 期
A randomized controlled open-label multicenter study to assess the efficacy of TCZ in treatment of late/chronic active antibody-mediated rejection in kidney transplant recipients
Vaestra Goetalandsregionen7 个研究点 分布在 2 个国家目标入组 65 人开始时间: 2024年3月1日最近更新:
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 65
- 试验地点
- 7
- 主要终点
- The primary efficacy endpoint is mean rate of change in eGFR decline from baseline to 24 months after start of treatment and at 1 month, then every 3 months for 36 months, and evaluating the results as a continuous variable using Modification of Diet for Renal Disease (MDRD) 4-variable equation, as it has been shown to better predict kidney function in kidney transplant recipients especially at low level of kidney function. Testing will be performed directly by accredited chemistry laboratories
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy of addition of TCZ to SOC as compared to SOC alone in slowing the decline of graft function from baseline at 24 months after start of treatment as assessed by estimated glomerular filtration rate (eGFR) in kidney transplant recipients with late/chronic active AMR.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •The subject has given their written informed consent to participate in the trial.
- •Recipient of living donor or deceased donor kidney transplant
- •Age ≥18 years
- •At least 6 months post-transplantation at randomization
- •Biopsy-proven diagnosis of late active (≥ 6 months posttransplant) or chronic active AMR according to the Banff 2022 criteria in index biopsy [Repeat biopsy and DSA-testing if required for diagnosis should be performed 2 months ± 2 weeks if the patient has received any treatment for AMR after the initial diagnostic biopsy or at randomization if the last biopsy is older than 12 months (+ 2 weeks) at randomization (Visit 2)].
- •eGFR ≥20 ml/min/1.73 m2 (not older than 1 month at randomization).
- •EBV IgG-positive
- •For female participants of childbearing potential: use of adequate contraception and a negative pregnancy test
- •Subject known to have been previously had COVID-19 must meet the following conditions: • Asymptomatic for at least 1 month before screening visit • Re-established on background immunosuppressants for at least 1 month prior to randomization
排除标准
- •Recipient of multi-organ transplants
- •Other significant liver disease as per Investigator’s opinion
- •Neutropenia (<2 x109/L) or thrombocytopenia (<100 x109/L)
- •Signs of malignancy. Exceptions are basal cell carcinoma/squamous cell carcinoma or non-malignant melanoma
- •History of malignancy, unless subject has been considered to have fully recovered from malignancy since > 2 years, without any signs of relapse
- •History of diverticulitis, inflammatory bowel disease (IBD) or gastrointestinal perforation
- •Ongoing alcohol or illicit substance abuse
- •Serious medical or psychiatric illness likely to interfere with participation in the study as per Investigator’s opinion
- •Mental inability or reluctance that result in difficulties in understanding the meaning of study participation
- •Woman of childbearing potential who is unwilling/unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of trial drug
- •Woman with a positive pregnancy test or who is pregnant or breastfeeding
- •De novo or recurrent renal disease, if it is considered to be the predominant cause of the current graft dysfunction
- •Current or recent (within last 3 months) participation in another clinical drug trial
- •Active viral infections such as BK virus (BKV), cytomegalovirus (CMV), SARS COV-2 (COVID-19), EBV, hepatitis C virus (HCV) or hepatitis B virus (HBV) infections, based on polymerase chain reaction (PCR) testing
- •Ongoing serious infections as per Investigator’s opinion
- •History of recurrent serious infections requiring hospitalization
- •Signs of post-transplant lymphoproliferative disorder
- •Active tuberculosis (TB)
- •Untreated latent TB (positive QuantiFERON-TB-Gold test, Chest X-ray)
- •Abnormal liver function tests alanine transaminase (ALT), aspartate transaminase (AST), bilirubin > 1.5 x upper limit of normal)
结局指标
主要结局
The primary efficacy endpoint is mean rate of change in eGFR decline from baseline to 24 months after start of treatment and at 1 month, then every 3 months for 36 months, and evaluating the results as a continuous variable using Modification of Diet for Renal Disease (MDRD) 4-variable equation, as it has been shown to better predict kidney function in kidney transplant recipients especially at low level of kidney function. Testing will be performed directly by accredited chemistry laboratories
The primary efficacy endpoint is mean rate of change in eGFR decline from baseline to 24 months after start of treatment and at 1 month, then every 3 months for 36 months, and evaluating the results as a continuous variable using Modification of Diet for Renal Disease (MDRD) 4-variable equation, as it has been shown to better predict kidney function in kidney transplant recipients especially at low level of kidney function. Testing will be performed directly by accredited chemistry laboratories
次要结局
- Change from baseline in mean composite iBox risk score at 12 and 24 months after start of treatment
- Incidence of patient survival at 12, 24 and 36 months after start of treatment
- Safety: incidence, nature and severity of adverse events (AE) and serious AE (SAE) during 24 months of treatment period
- Evolution of DSA, as assessed by appearance of new DSA, and change in strength of both immunodominant (iDSA) and cumulative DSA (cDSA), measured as MFI, from baseline at 12, 24 and 36 months after start of treatment
- Histologic changes from baseline in protocol biopsy at 12 and 24 months after start of treatment
- Changes from baseline in proteinuria at 12, 24 and 36 months after start of treatment, as assessed by urine albumin/creatinine ratio (UACR)
- Changes from baseline in renal function at 12, 24 and 36 months after start of treatment, as assessed by mGFR using iohexol clearance
- Changes from baseline in renal function at 12 and 36 months after start of treatment, as assessed by eGFR
- Incidence of graft survival (overall and death-censored) at 12, 24 and 36 months after start of treatment
- Incidence of acute rejection (overall and by biopsy‐proven/clinical diagnosis), its type and Banff-grade if biopsy-proven at 12, 24 and 36 months after start of treatment
- Incidence and Banff-grade of new chronic active T-cell mediated rejection at 12, 24 and 36 months after start of treatment
- Experienced transplant-specific well-being, symptom burden, perceived threat of the risk of graft rejection and adherence to immunosuppressive medications at baseline,12, 24 and 36 months after start of treatment, and possible changes from baseline at each time-point as well as in comparison with other transplant recipients not suffering
- Sex-, occupation-, civil- and educational status-related differences in transplant-specific well-being, symptom burden, perceived threat of the risk of graft rejection and adherence to immunosuppressive medications at baseline, 12, 24 and 36 months as well as in comparison with other transplant recipients not suffering
研究者
Seema Baid-Agrawal
Scientific
Vaestra Goetalandsregionen
研究点 (7)
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