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

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 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.

Study Overview

• Status: Recruiting
• Conditions: Antibody-mediated Rejection
• Intervention / Treatment: Drug: Tocilizumab

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Marie Felldin, MD, PhD; Phone Number: +4631-342 10 00; Email: marie.felldin@surgery.gu.se
• Study Contact Backup: Name: Seema Baid-Agrawal, MD, FASN; Phone Number: +4631-342 10 00; Email: seema.baid-agrawal@vgregion.se

Study Locations

• Spain
  • A Coruña, Spain
    • Not yet recruiting
    • Complejo Hospitalario Universitario A Coruna
    • Contact: Constantino Fernández Rivera, MD. PhD; Phone Number: +34 981 178 159; Email: Constantino.Fernandez.Rivera@sergas.es
    • Principal Investigator: Constantino Fernández Rivera, MD, PhD
  • Barcelona, Spain
    • Active, not recruiting
    • Hospital del Mar
  • Santander, Spain
    • Not yet recruiting
    • Marqués de Valdecilla Research Institute
    • Contact: Juan Carlos Ruíz San Millán, MD. PhD; Phone Number: +34 942 202738; Email: juancarlos.ruiz@scsalud.es
    • Principal Investigator: Juan Carlos Ruíz San Millán, MD. PhD
  • Valencia, Spain
    • Not yet recruiting
    • Hospital Universitario Dr. Peset
    • Contact: Asunción Sancho Calabuig, MD, PhD; Phone Number: +34 648 012 408; Email: asanchoc2@gmail.com
    • Principal Investigator: Asunción Sancho Calabuig, MD. PhD
• Sweden
  • Stockholm, Sweden, SE-141 86
    • Recruiting
    • Karolinksa University Hospital
    • Contact: Lars Wennberg, MD, PhD; Phone Number: +46 8 5858 2554; Email: lars.wennberg@sll.se
    • Principal Investigator: Lars Wennberg, MD. PhD
    • Sub-Investigator: Jessica Smolander, MD
  • Uppsala, Sweden, 751 85
    • Recruiting
    • Uppsala University Hospital
    • Contact: Tomas Lorant, MD, PhD; Phone Number: +46 18 611 7080; Email: Tomas.Lorant@surgsci.uu.se
    • Contact: Bengt Felldström, MD, PhD; Email: bengt.fellstrom@medsci.uu.se
    • Principal Investigator: Tomas Lorant, MD. PhD
  • Skåne
    • Malmo, Skåne, Sweden, 214 28
      • Recruiting
      • Skåne University Hospital
      • Contact: Carin Wallquist, MD, PhD; Email: Carin.Wallquist@skane.se
      • Principal Investigator: Carin Wallquist, MD, PhD
  • Vastra Gotaland Regioin
    • Gothenburg, Vastra Gotaland Regioin, Sweden
      • Recruiting
      • Transplant Center, Sahlgrenska University Hospital
      • Contact: Seema Baid-Agrawal, MD; Phone Number: 031-342 10 00; Email: seema.baid-agrawal@vgregion.se
      • Contact: Marie Felldin, MD, PhD; Phone Number: 031-342 10 00; Email: marie.felldin@surgery.gu.se
      • Sub-Investigator: Jana Ekberg, MD
      • Sub-Investigator: Lars Mjornstedt, MD, PhD
      • Sub-Investigator: Per Lindnér, MD, PhD
      • Sub-Investigator: Marie Felldin, MD, PhD
      • Sub-Investigator: Lillian Streichart, MD
      • Sub-Investigator: Annette Lennerling, RN, PhD
      • Sub-Investigator: Verena Bröcker, MD
      • Sub-Investigator: Johan Mölne, MD, PhD
      • Sub-Investigator: Jan Holgersson, MD, PhD
      • Sub-Investigator: Jenny Nyström, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 96 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A: Standard of care (SOC) + tocilizumab (TCZ); SOC, as below + TCZ (162 mg every week, subcuataneous administration)	Drug: Tocilizumab; Tocilizumab is a recombinant humanized monoclonal antibody directed against the human interleukin-6 (IL-6) receptor; Other Names: RoActemra
No Intervention: Arm B: SOC; Tacrolimus (target concentration 6 ±1 µg/L) + MPA (1.5-2 g/day as tolerated) + prednisolone (not less than 5 mg/day), all oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Changes in proteinuria	Assessed by urine albumin creatinine ratio (UACR) at baseline and every 12 months	baseline and up to 36 months
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
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
Patient survival	Incidence of patient survival at 12, 24 and 36 months after start of treatment	up to 36 months
Death-censored graft survival	Incidence of death-censored graft survival at 12, 24 and 36 months after start of treatment	up to 36 months
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
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
Possible change in adherence to immunosuppressive medications	Assessed using a validated self-reported questionnaires at baseline and every 12 months	upto 36 months
Composite risk prediction score iBox	Efficacy of the treatment regimen by assessing the iBox score	baseline and upto 24 months
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 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	baseline and up to 24 months

Collaborators and Investigators

• Sponsor: Vastra Gotaland Region
• Collaborators: Karolinska University Hospital; The Swedish Research Council; Hospital del Mar; Skane University Hospital; Uppsala University Hospital; Hospital Universitario Doctor Peset; Hospital Universitario Marqués de Valdecilla; Complexo Hospitalario Universitario de A Coruña
• Investigators: Principal Investigator: Seema Baid-Agrawal, MD, FASN, Transplant Center, Sahlgrenska University Hospital, Gothenburg, Sweden

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: September 3, 2020
• First Submitted That Met QC Criteria: September 22, 2020
• First Posted (Actual): September 24, 2020

Study Record Updates

• Last Update Posted (Actual): April 3, 2025
• Last Update Submitted That Met QC Criteria: March 31, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Adherence; Chronic rejection; Kidney transplant; Antibody-mediated rejection; Graft function; Donor specific antibodies (DSA); Transplant-specific well-being
• Other Study ID Numbers: 2019-004302-10; 2024-510615-29-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No