Clinical trial NCT04561986: TocIlizumab in Late/Chronic Active Antibody-mediated Rejection in Kidney Transplant Recipients
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Antibody-mediated Rejection
Keywords: Kidney transplant
Chronic rejection
Antibody-mediated rejection
Graft function
Donor specific antibodies (DSA)
Transplant-specific well-being
Adherence
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
Collaborators: name: Karolinska University Hospital
name: Uppsala University Hospital
name: Skane University Hospital
name: The Swedish Research Council
name: Hospital del Mar
name: Hospital Universitario Doctor Peset
name: Complexo Hospitalario Universitario de A Coruña
name: Hospital Universitario Marqués de Valdecilla
First posted: 2020-09-24
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


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

Primary outcomes:
measure: Change from baseline in eGFR at 24 months
timeFrame: Baseline and 24 months
Secondary outcomes:
measure: Composite risk prediction score iBox
timeFrame: baseline and upto 24 months
measure: Incidence of adverse and serious events related to TCZ treatment
timeFrame: up to 25 months
measure: Change in Donor-specific anti-HLA antibodies (DSA)
timeFrame: baseline and up to 36 months
measure: Histologic changes in protocol biopsy
timeFrame: baseline and up to 24 months
measure: Changes in proteinuria
timeFrame: baseline and up to 36 months
measure: Renal function assessed by measured GFR (mGFR)
timeFrame: baseline and up to 36 months
measure: Renal function assessed by eGFR
timeFrame: baseline and up to 36 months
measure: Patient survival
timeFrame: up to 36 months
measure: Death-censored graft survival
timeFrame: up to 36 months
measure: Possible change in experienced transplant-specific well-being and symptom burden
timeFrame: upto 36 months
measure: Possible change in experienced perceived threat of the risk of graft rejection
timeFrame: upto 36 months
measure: Possible change in adherence to immunosuppressive medications
timeFrame: upto 36 months
Other outcomes:
Locations:
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Santander
country: Spain
facility: Marqués de Valdecilla Research Institute
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset
city: Malmo
country: Sweden
facility: Skåne University Hospital
state: Skåne
city: Gothenburg
country: Sweden
facility: Transplant Center, Sahlgrenska University Hospital
state: Vastra Gotaland Regioin
city: Stockholm
country: Sweden
facility: Karolinksa University Hospital
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
Study officials:
affiliation: Transplant Center, Sahlgrenska University Hospital, Gothenburg, Sweden
name: Seema Baid-Agrawal, MD, FASN
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.