Using Tocilizumab to Treat Chronic Antibody-mediated Rejection in Kidney Transplant Patients

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

This study is testing if adding tocilizumab to standard treatment can help kidney transplant patients who are experiencing chronic rejection feel better and improve their kidney function.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: Vastra Gotaland Region (Government)
• Drugs / interventions: tocilizumab
• Locations: 8 sites (A Coruña and 7 other locations)
• Trial ID: NCT04561986 on ClinicalTrials.gov

What this trial studies

This multi-center clinical trial aims to evaluate the effectiveness of tocilizumab, an anti-IL-6 antibody, when added to standard care in kidney transplant recipients experiencing late or chronic antibody-mediated rejection. A total of 50 participants will be randomly assigned to receive either tocilizumab plus standard care or standard care alone for 24 months, with follow-up for an additional year. The primary outcome will be the change in graft function, measured by the estimated glomerular filtration rate (eGFR) over the treatment period. Biopsy assessments will be conducted at 12 and 24 months to monitor graft health.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older who have undergone kidney transplantation and have a biopsy-proven diagnosis of late or chronic antibody-mediated rejection.

Not a fit: Patients who have received multi-organ transplants or have predominant renal disease unrelated to rejection may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve graft function and longevity in kidney transplant recipients facing chronic rejection.

How similar studies have performed: While the use of tocilizumab in this context is novel, previous studies have shown promise in using IL-6 inhibitors for various autoimmune conditions, suggesting potential for success.

Eligibility criteria

Inclusion Criteria:

1. The subject has given their written informed consent to participate in the study
2. Recipient of living donor or deceased donor kidney transplant
3. Age ≥18 years
4. At least 6 months post-transplantation at randomization
5. Biopsy-proven diagnosis of late active or chronic active ABMR (≥ 6 months after transplantation) according to the Banff 2022 criteria in index biopsy
6. eGFR ≥20 ml/min/1.73 m2
7. Epstein-Barr Virus (EBV) IgG-positive
8. For female participants of childbearing potential:

   * use of adequate contraception and a negative pregnancy test
9. 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

Exclusion Criteria:

1. Recipient of multi-organ transplants
2. De novo or recurrent renal disease that is considered to be the predominant cause of the current graft dysfunction
3. 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
4. Ongoing serious infections as per Investigator's opinion
5. History of recurrent infections requiring hospitalization
6. Active tuberculosis (TB)
7. Latent untreatedTB (positive QuantiFERON-TB-Gold test, Chest X-ray)
8. Abnormal liver function tests alanine transaminase (ALT), aspartate transaminase (AST), bilirubin \> 1.5 x upper limit of normal)
9. Other significant liver disease as per Investigator's opinion
10. Neutropenia (\<2 x109/L) or thrombocytopenia (\<100 x109/L)
11. Signs of post-transplant lymphoproliferative disorder
12. Signs of malignancy. Exceptions are basal cell carcinoma/squamous cell carcinoma or non-malignant melanoma
13. History of malignancy, unless subject has been considered to have fully recovered from malignancy since \> 2 years, without any signs of relapse
14. History of diverticulitis, inflammatory bowel disease or gastrointestinal perforation
15. Ongoing alcohol or illicit substance abuse
16. Serious medical or psychiatric illness likely to interfere with participation in the study as per Investigator's opinion
17. Mental inability or reluctance that results in difficulties in understanding the meaning of study participation
18. 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
19. Woman with a positive pregnancy test or who is pregnant or breastfeeding
20. Current or recent (within last 3 months) participation in another clinical drug trial

Where this trial is running

A Coruña and 7 other locations

• Complejo Hospitalario Universitario A Coruña — A Coruña, Spain (Not_yet_recruiting)
• Hospital del Mar — Barcelona, Spain (Active_not_recruiting)
• Marqués de Valdecilla Research Institute — Santander, Spain (Not_yet_recruiting)
• Hospital Universitario Dr. Peset — Valencia, Spain (Not_yet_recruiting)
• Skåne University Hospital — Malmö, Skåne County, Sweden (Recruiting)
• Transplant Center, Sahlgrenska University Hospital — Gothenburg, Vastra Gotaland Regioin, Sweden (Recruiting)
• Karolinksa University Hospital — Stockholm, Sweden (Recruiting)
• Uppsala University Hospital — Uppsala, Sweden (Recruiting)

Study contacts

• Principal investigator: Seema Baid-Agrawal, MD, FASN — Transplant Center, Sahlgrenska University Hospital, Gothenburg, Sweden
• Study coordinator: Seema Baid-Agrawal, MD, FASN

Conditions Antibody-mediated Rejection; Kidney transplant; Chronic rejection; Antibody-mediated rejection; Graft function; Donor specific antibodies; Transplant-specific well-being; Adherence