Treatment of chronic active antibody-mediated rejection in kidney transplant recipients MedDRA version: 20.0 Level: PT Classification code 10023439 Term: Kidney transplant rejection System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Trade Name: RoActemra
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Roactemra
CAS Number: 375823-41-9
Other descriptive name: TOCILIZUMAB
Concentration unit: mg mi
Sponsors
Västra Götalandsregionen, Sahlgrenska University hospital
Eligibility
Sex/Gender
All
Inclusion criteria
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. Repeat biopsy should be performed if the last biopsy is estimated to be older than 6 months (+ 2 weeks) at the projected time of randomization (Visit 2) 6. GFR =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 been previously had corona virus disease of 2019 (COVID-19) must meet all of the following conditions: - Asymptomatic for at least 1 month before the start of screening - Re-established on maintenance immunosuppressants for at least 2 weeks prior to the start of screening Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 44 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
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, in the Investigator’s opinion, could adversely influence the current allograft 4. Active viral infections such as BK virus (BKV), cytomegalovirus (CMV), SARS COV-2 (COVID-19), EBV, 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 serious infections requiring hospitalization 7. Signs of post-transplant lymphoproliferative disorder 8. History of tuberculosis (TB) 9. Active TB or latent TB (positive QuantiFERON-TB-Gold test, Chest X-ray) 10. Abnormal liver function tests alanine transaminase (ALT), aspartate transaminase (AST), bilirubin > 1.5 x upper limit of normal) 11. Other significant liver disease as per Investigator’s opinion 12. Neutropenia ( 2 years, without any signs of relapse 15. History of diverticulitis, diverticulosis, gastrointestinal perforation or inflammatory bowel disease 16. Ongoing 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, reluctance or language difficulties that result in difficulty 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of addition of TCZ to SOC as compared to SOC alone in reducing the decline of graft function from baseline at 24 months after start of treatment as measured by estimated glomerular filtration rate (eGFR) in kidney transplant recipients with cAMR ;Secondary Objective: 1.To assess the safety of TCZ for the treatment of cAMR during 24 months of treatment period 2.To compare the efficacy between treatment regimens by assessing the differences in: -Evolution of DSA and its strength (mean fluorescence intensity, MFI) at 12, 24 and 36 months -Graft histology at 12 and 24 months -Proteinuria at 12, 24 and 36 months -Renal function assessed by measured GFR (mGFR) at 12, 24 and 36 months -Renal function assessed by eGFR at 12 and 36 months -Patient survival at 12, 24 and 36 months -Overall and death-censored graft survival at 12, 24 and 36 months 3.To assess transplant-specific well-being, adherence to immunosuppressive medications and perceived threat of the risk of graft rejection in the included patients at 12, 24 and 36 months 4.To identify sex-related differences in responsiveness and adherence to immunosuppressive treatment, symptom burden and transplant-specific well-being at 12, 24 and 36 months ;Primary end point(s): Mean rate of change in eGFR (eGFR slope) from baseline to 24 months after start of treatment ;Timepoint(s) of evaluation of this end point: 24 months after start of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary end points: 1. Safety: incidence, nature and severity of adverse events (AE) and serious AE (SAE) during 24 months of treatment period 2. Evolution of DSA, as assessed by appearance of new DSA, and change in strength of both immunodominant (iDSA) and cumulative DSA (cDSA), measured as MFI, from baseline at 12, 24 and 36 months after start of treatment 3. Histologic changes from baseline in protocol biopsy at 12 and 24 months after start of treatment 4. Changes from baseline in proteinuria at 12, 24 and 36 months after start of treatment, as assessed by UACR 5. Changes from baseline in renal function at 12, 24 and 36 months after start of treatment, as assessed by mGFR using iohexol clearance 6. Changes from baseline in renal function at 12 and 36 months after start of treatment, as assessed by eGFR 7. Incidence of patient survival at 12, 24 and 36 months after start of treatment 8. Incidence of graft survival (overall and death-censored) at 12, 24 and 36 months after start of treatment 9. Possible changes of experienced transplant-specific well-being, symptom burden, perceived threat of the risk of graft rejection and adherence to immunosuppressive medications at 12, 24 and 36 months after start of treatment Exploratory endpoints: 1. Characteristics of DSA (strength-MFI, class, IgG subclass, ability to fix C1q) at baseline and their correlation with clinical and histologic phenotypes of cAMR, responsiveness to therapy and outcomes at 24 months after start of treatment 2. Novel histologic, immunologic, molecular and genetic biomarkers in plasma/ urine and protocol biopsies at baseline and at 24 months for risk stratification for graft ;Timepoint(s) of evaluation of this end point: 12, 24 and 36 months | — |
Countries
Sweden
Contacts
Public ContactSeema Baid-Agrawal
Sahlgrenska University Hospital, Västra götalandsregionen
Outcome results
None listed