TocIlizumab in Chronic Antibody-mediated Rejection in Kidney Transplant Recipients

Antibody-mediated Rejection Clinical Trial

— INTERCEPT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04561986
• Other study ID #: 2019-004302-10
• Status: Recruiting
• Phase: Phase 3
• Start date: February 1, 2022
• Est. completion date: December 2027

Study information

• Verified date: November 2023
• Source: Vastra Gotaland Region
• Contact: Seema Baid-Agrawal, MD, FASN
• Phone: +4631-342 10 00
• Email: seema.baid-agrawal[@]vgregion.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 chronic antibody-mediated rejection (cAMR). 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2027
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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 12 months post-transplantation at randomization

5. Biopsy-proven diagnosis of cAMR according to the Banff 2017 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. Inability to tolerate any of the SOC treatment- tacrolimus, mycophenolate acid (MPA) or prednisolone

2. Recipient of multi-organ transplants

3. De novo or recurrent renal disease that is considered to be the predominant cause of the current graft dysfunction

4. 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

5. Ongoing serious infections as per Investigator's opinion

6. History of recurrent infections requiring hospitalization

7. History of tuberculosis (TB)

8. Active TB or latent TB (positive QuantiFERON-TB-Gold test, Chest X-ray)

9. Abnormal liver function tests alanine transaminase (ALT), aspartate transaminase (AST), bilirubin > 1.5 x upper limit of normal)

10. Other significant liver disease as per Investigator's opinion

11. Neutropenia (<2 x109/L) or thrombocytopenia (<100 x109/L)

12. Signs of post-transplant lymphoproliferative disorder

13. Signs of malignancy. Exceptions are basal cell carcinoma/squamous cell carcinoma or non-malignant melanoma

14. History of malignancy, unless subject has been considered to have fully recovered from malignancy since > 2 years, without any signs of relapse

15. History of diverticulitis, inflammatory bowel disease or gastrointestinal perforation

16. Active alcohol or illicit substance abuse

17. Serious medical or psychiatric illness likely to interfere with participation in the study as per Investigator's opinion

18. Mental inability that results in difficulties in understanding the meaning of study participation

19. 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

20. Woman with a positive pregnancy test or who is pregnant or breastfeeding

21. Current or recent (within last 3 months) participation in another clinical drug trial

Related Conditions & MeSH terms

• Antibody-mediated Rejection

Intervention

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

Locations

Country	Name	City	State
Sweden	Transplant Center, Sahlgrenska University Hospital	Gothenburg	Vastra Gotaland Regioin
Sweden	Skåne University Hospital	Malmo	Skåne
Sweden	Karolinksa University Hospital	Stockholm
Sweden	Uppsala University Hospital	Uppsala

Sponsors (5)

Lead Sponsor	Collaborator
Vastra Gotaland Region	Karolinska University Hospital, Skane University Hospital, The Swedish Research Council, Uppsala University Hospital

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in eGFR at 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).	Baseline and 24 months
Secondary	Composite risk prediction score iBox	Efficacy of the treatment regimen by assessing the iBox score	baseline and upto 24 months
Secondary	Incidence of adverse and serious events related to TCZ treatment	Assessments of incidence of any side effects including infectious complications associated with TCZ therapy	up to 25 months
Secondary	Change in Donor-specific anti-HLA antibodies (DSA)	Change in DSA from baseline based on luminex assessments every 12 months	baseline and up to 36 months
Secondary	Histologic changes in protocol biopsy	Histologic changes at 12 and 24 months will be compared with those in the baseline biopsies. If the criteria for cAMR 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 cAMR, means of individual Banff lesion scores will be compared between the baseline biopsy and the 12- and 24-months biopsies	baseline and up to 24 months
Secondary	Changes in proteinuria	Assessed by urine albumin creatinine ratio (UACR) at baseline and every 12 months	baseline and up to 36 months
Secondary	Renal function assessed by measured GFR (mGFR)	Changes from baseline in renal function as assessed by mGFR using iohexol clearance	baseline and up to 36 months
Secondary	Renal function assessed by eGFR	Changes from baseline in renal function at 12 and 36 months after start of treatment, as assessed by eGFR (CKD-EPI)	baseline and up to 36 months
Secondary	Patient survival	Incidence of patient survival at 12, 24 and 36 months after start of treatment	up to 36 months
Secondary	Death-censored graft survival	Incidence of death-censored graft survival at 12, 24 and 36 months after start of treatment	up to 36 months
Secondary	Possible change in experienced transplant-specific well-being and symptom burden	Assessed using a validated self-reported questionnaires at baseline and every 12 months	upto 36 months
Secondary	Possible change in experienced perceived threat of the risk of graft rejection	Assessed using a validated self-reported questionnaires at baseline and every 12 months	upto 36 months
Secondary	Possible change in adherence to immunosuppressive medications	Assessed using a validated self-reported questionnaires at baseline and every 12 months	upto 36 months