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NCT Number: NCT04561986

TocIlizumab in 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.

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Key information

Conditions

Antibody-mediated Rejection

Age range

18 year–100 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Complejo Hospitalario Universitario A Coruña, A Coruña, Spain

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

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

Treatment and study plan

Tocilizumab

Drug

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

Other names: RoActemra

Primary outcomes

  1. Change from baseline in eGFR at 24 months

    Time frame: 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 outcomes

  1. Composite risk prediction score iBox

    Time frame: baseline and upto 24 months

    Efficacy of the treatment regimen by assessing the iBox score

  2. Incidence of adverse and serious events related to TCZ treatment

    Time frame: up to 25 months

    Assessments of incidence of any side effects including infectious complications associated with TCZ therapy

  3. Change in Donor-specific anti-HLA antibodies (DSA)

    Time frame: baseline and up to 36 months

    Change in DSA from baseline based on luminex assessments every 12 months

  4. Histologic changes in protocol biopsy

    Time frame: 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

  5. Changes in proteinuria

    Time frame: baseline and up to 36 months

    Assessed by urine albumin creatinine ratio (UACR) at baseline and every 12 months

  6. Renal function assessed by measured GFR (mGFR)

    Time frame: baseline and up to 36 months

    Changes from baseline in renal function as assessed by mGFR using iohexol clearance

  7. Renal function assessed by eGFR

    Time frame: 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)

  8. Patient survival

    Time frame: up to 36 months

    Incidence of patient survival at 12, 24 and 36 months after start of treatment

  9. Death-censored graft survival

    Time frame: up to 36 months

    Incidence of death-censored graft survival at 12, 24 and 36 months after start of treatment

  10. Possible change in experienced transplant-specific well-being and symptom burden

    Time frame: upto 36 months

    Assessed using a validated self-reported questionnaires at baseline and every 12 months

  11. Possible change in experienced perceived threat of the risk of graft rejection

    Time frame: upto 36 months

    Assessed using a validated self-reported questionnaires at baseline and every 12 months

  12. Possible change in adherence to immunosuppressive medications

    Time frame: upto 36 months

    Assessed using a validated self-reported questionnaires at baseline and every 12 months

Study contacts

Contact information is provided by the study sponsor or research team.

Marie Felldin, MD, PhD

CONTACT

[email protected]

+4631-342 10 00

Seema Baid-Agrawal, MD, FASN

CONTACT

[email protected]

+4631-342 10 00

Sponsors and collaborators

Lead sponsor

Vastra Gotaland Region

Other Gov

Collaborators

  • Complexo Hospitalario Universitario de A Coruña
  • Hospital Universitario Doctor Peset
  • Hospital Universitario Marqués de Valdecilla
  • Hospital del Mar
  • Karolinska University Hospital
  • Skane University Hospital
  • The Swedish Research Council
  • Uppsala University Hospital

Registry information

Official study 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

Acronym: INTERCEPT

Important dates

Study start
2022
Primary completion
2027
Study completion
2028
First posted
Sep 24, 2020
Registry last updated
Apr 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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