TocIlizumab in Late/Chronic Active Antibody-mediated Rejection in Kidney Transplant Recipients

Официальное название

A Randomized Controlled Open-label Multi-center Study to Assess the Efficacy of TCZ in Treatment of Late/Chronic Active Antibody-mediated Rejection in Kidney Transplant Recipients

Обзор

This multi-center study is an investigator-driven randomized controlled parallel group open-label clinical trial designed to evaluate the efficacy of addition of anti-IL-6 antibody tocilizumab (TCZ) to the standard of care (SOC) treatment as compared to the SOC alone in reducing the decline of graft function in kidney transplant recipients with late or chronic antibody-mediated rejection (AMR). A total of 50 recipients will be allocated to receive either TCZ (n=25) added to the standard of care (SOC) or SOC alone (n=25) for a period of 24 months. Patients will be followed for an additional 12 months. Protocol kidney graft biopsies will be performed at 12 and 24 months. The primary outcome is the mean rate of change in graft function as assessed by estimated glomerular filtration rate (eGFR) slope from baseline to 24 months after start of treatment.

Вмешательства

• Препарат Tocilizumab
  Tocilizumab is a recombinant humanized monoclonal antibody directed against the human interleukin-6 (IL-6) receptor

Первичные конечные точки

• Change from baseline in eGFR at 24 months [Срок оценки: Baseline and 24 months]

Вторичные конечные точки (12)

• Composite risk prediction score iBox [Срок оценки: baseline and upto 24 months]
• Incidence of adverse and serious events related to TCZ treatment [Срок оценки: up to 25 months]
• Change in Donor-specific anti-HLA antibodies (DSA) [Срок оценки: baseline and up to 36 months]
• Histologic changes in protocol biopsy [Срок оценки: baseline and up to 24 months]
• Changes in proteinuria [Срок оценки: baseline and up to 36 months]
• Renal function assessed by measured GFR (mGFR) [Срок оценки: baseline and up to 36 months]
• Renal function assessed by eGFR [Срок оценки: baseline and up to 36 months]
• Patient survival [Срок оценки: up to 36 months]
• Death-censored graft survival [Срок оценки: up to 36 months]
• Possible change in experienced transplant-specific well-being and symptom burden [Срок оценки: upto 36 months]
• Possible change in experienced perceived threat of the risk of graft rejection [Срок оценки: upto 36 months]
• Possible change in adherence to immunosuppressive medications [Срок оценки: upto 36 months]

Критерии участия

Критерии включения

• The subject has given their written informed consent to participate in the study
• 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 or chronic active ABMR (≥ 6 months after transplantation) according to the Banff 2022 criteria in index biopsy
• eGFR ≥20 ml/min/1.73 m2
• Epstein-Barr Virus (EBV) IgG-positive
• For female participants of childbearing potential:

• use of adequate contraception and a negative pregnancy test
• Subject known to have COVID-19 previously must meet all of the following conditions:

• Asymptomatic for at least 1 month before the start of screening
• Re-established on background immunosuppressants for at least 1 month prior to the randomization

Критерии исключения

• Recipient of multi-organ transplants
• De novo or recurrent renal disease that is considered to be the predominant cause of the current graft dysfunction
• Active viral infections such as BK virus (BKV), cytomegalovirus (CMV), EBV, COVID-19, 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 infections requiring hospitalization
• Active tuberculosis (TB)
• Latent untreatedTB (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)
• Other significant liver disease as per Investigator's opinion
• Neutropenia (<2 x109/L) or thrombocytopenia (<100 x109/L)
• Signs of post-transplant lymphoproliferative disorder
• 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 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 results 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 study drug
• Woman with a positive pregnancy test or who is pregnant or breastfeeding
• Current or recent (within last 3 months) participation in another clinical drug trial

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Испания · 4 центра

• Complejo Hospitalario Universitario A Coruña — A Coruña
• Hospital del Mar — Barcelona
• Marqués de Valdecilla Research Institute — Santander
• Hospital Universitario Dr. Peset — Valencia

Швеция · 4 центра

• Skåne University Hospital — Malmö
• Transplant Center, Sahlgrenska University Hospital — Gothenburg
• Karolinksa University Hospital — Stockholm
• Uppsala University Hospital — Uppsala

Публикации

• Streichart L, Felldin M, Ekberg J, Mjornstedt L, Lindner P, Lennerling A, Brocker V, Molne J, Holgersson J, Daenen K, Wennberg L, Lorant T, Baid-Agrawal S. Tocilizumab in chronic active antibody-mediated rejection: rationale and protocol of an in-progress randomized controlled open-label multi-center trial (INTERCEPT study). Trials. 2024 Mar 22;25(1):213. doi: 10.1186/s13063-024-08020-0. PMID 38519988

Идентификаторы

NCT: NCT04561986 · 2019-004302-10 · 2024-510615-29-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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