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

NCT04561986 | Recruiting Phase 3 DMC

• 2 other identifiers: 2019-004302-102024-510615-29-00
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 8

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.

Conditions

Antibody-mediated Rejection

Keywords

Kidney transplant; Chronic rejection; Antibody-mediated rejection; Graft function; Donor specific antibodies (DSA); Transplant-specific well-being; Adherence

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• Composite risk prediction score iBox

  baseline and upto 24 months

• Incidence of adverse and serious events related to TCZ treatment

  up to 25 months

• Change in Donor-specific anti-HLA antibodies (DSA)

  baseline and up to 36 months

• Histologic changes in protocol biopsy

  baseline and up to 24 months

• Changes in proteinuria

  baseline and up to 36 months

Study Arms (2)

Arm A: Standard of care (SOC) + tocilizumab (TCZ)

ACTIVE COMPARATOR

SOC, as below + TCZ (162 mg every week, subcuataneous administration)

Drug: Tocilizumab

Arm B: SOC

NO INTERVENTION

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

Interventions

Tocilizumab DRUG

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

Also known as: RoActemra

Arm A: Standard of care (SOC) + tocilizumab (TCZ)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vastra Gotaland Region: lead
• Karolinska University Hospital: collaborator
• Uppsala University Hospital: collaborator
• Skane University Hospital: collaborator
• The Swedish Research Council: collaborator
• Hospital del Mar: collaborator
• Hospital Universitario Doctor Peset: collaborator
• Complexo Hospitalario Universitario de A Coruña: collaborator
• Hospital Universitario Marqués de Valdecilla: collaborator

Study Sites (8)

Complejo Hospitalario Universitario A Coruña

A Coruña, Spain

NOT YET RECRUITING

Hospital del Mar

Barcelona, Spain

ACTIVE NOT RECRUITING

Marqués de Valdecilla Research Institute

Santander, Spain

NOT YET RECRUITING

Hospital Universitario Dr. Peset

Valencia, Spain

NOT YET RECRUITING

Skåne University Hospital

Malmo, Skåne County, 214 28, Sweden

RECRUITING

Transplant Center, Sahlgrenska University Hospital

Gothenburg, Vastra Gotaland Regioin, Sweden

RECRUITING

Karolinksa University Hospital

Stockholm, SE-141 86, Sweden

RECRUITING

Uppsala University Hospital

Uppsala, 751 85, Sweden

RECRUITING

Related Publications (1)

• 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.

  PMID: 38519988 BACKGROUND

MeSH Terms

Interventions

tocilizumab

Study Officials

• Seema Baid-Agrawal, MD, FASN

  Transplant Center, Sahlgrenska University Hospital, Gothenburg, Sweden

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Seema Baid-Agrawal, MD, FASN

CONTACT

+4631-342 10 00; seema.baid-agrawal@vgregion.se

Marie Felldin, MD, PhD

CONTACT

+4631-342 10 00; marie.felldin@surgery.gu.se

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor and Consultant Nephrologist, Transplantation Center, Sahlgrenska University Hospital, Gothenburg

Study Record Dates

• First Submitted: September 3, 2020
• First Posted: September 24, 2020
• Study Start: February 1, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 3, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4); SE (4)