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

Phase 3

Recruiting

• Conditions: Antibody-mediated Rejection
• Interventions: Drug: Tocilizumab

• Registration Number: NCT04561986
• Lead Sponsor: Vastra Gotaland Region

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-09-03
• Study First Submitted QC: 2020-09-22
• Study First Posted: 2020-09-24
• Study Start: 2022-02-01
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-31
• Last Update Posted: 2025-04-03
• Primary Completion: 2027-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: Standard of care (SOC) + tocilizumab (TCZ)	Tocilizumab	SOC, as below + TCZ (162 mg every week, subcuataneous administration)

Primary Outcome Measures

Name	Time	Method
Change from baseline in eGFR at 24 months	Baseline and 24 months	Comparison of eGFR decline (eGFR slope) from baseline at 24 months after start of treatment in the two arms. The eGFR will be assessed by measured creatinine values using MDRD formula in mL/min/1.73m\^2. MDRD formula is based on age, sex, ethnicity, and serum creatinine (in mg/dl) and eGFR values are calculated as follows: GFR in mL/min per 1.73 m\^2 = 175 x Serum Cr\^1.154 x age\^-0.203 x 1.212 (if patient is black) x 0.742 (if female).

Secondary Outcome Measures

Name	Time	Method
Composite risk prediction score iBox	baseline and upto 24 months	Efficacy of the treatment regimen by assessing the iBox score
Incidence of adverse and serious events related to TCZ treatment	up to 25 months	Assessments of incidence of any side effects including infectious complications associated with TCZ therapy
Change in Donor-specific anti-HLA antibodies (DSA)	baseline and up to 36 months	Change in DSA from baseline based on luminex assessments every 12 months
Histologic changes in protocol biopsy	baseline and up to 24 months	Histologic changes at 12 and 24 months will be compared with those in the baseline biopsies. If the criteria for active AMR are no longer fulfilled in the follow-up biopsies, response to therapy is assumed. The response will be assessed as a yes/no categorical variable. In all biopsies, which still meet the required criteria for active AMR, means of individual Banff lesion scores will be compared between the baseline biopsy and the 12- and 24-months biopsies
Changes in proteinuria	baseline and up to 36 months	Assessed by urine albumin creatinine ratio (UACR) at baseline and every 12 months
Renal function assessed by measured GFR (mGFR)	baseline and up to 36 months	Changes from baseline in renal function as assessed by mGFR using iohexol clearance
Renal function assessed by eGFR	baseline and up to 36 months	Changes from baseline in renal function at 12 and 36 months after start of treatment, as assessed by eGFR (CKD-EPI)
Patient survival	up to 36 months	Incidence of patient survival at 12, 24 and 36 months after start of treatment
Death-censored graft survival	up to 36 months	Incidence of death-censored graft survival at 12, 24 and 36 months after start of treatment
Possible change in experienced transplant-specific well-being and symptom burden	upto 36 months	Assessed using a validated self-reported questionnaires at baseline and every 12 months
Possible change in experienced perceived threat of the risk of graft rejection	upto 36 months	Assessed using a validated self-reported questionnaires at baseline and every 12 months
Possible change in adherence to immunosuppressive medications	upto 36 months	Assessed using a validated self-reported questionnaires at baseline and every 12 months

Trial Locations

Locations (8)

Complejo Hospitalario Universitario A Coruña; 🇪🇸 A Coruña, Spain

Hospital del Mar; 🇪🇸 Barcelona, Spain

Marqués de Valdecilla Research Institute; 🇪🇸 Santander, Spain

Hospital Universitario Dr. Peset; 🇪🇸 Valencia, Spain

Skåne University Hospital; 🇸🇪 Malmo, Skåne, Sweden

Transplant Center, Sahlgrenska University Hospital; 🇸🇪 Gothenburg, Vastra Gotaland Regioin, Sweden

Karolinksa University Hospital; 🇸🇪 Stockholm, Sweden

Uppsala University Hospital; 🇸🇪 Uppsala, Sweden