INTERCEPT: TocIlizumab in Chronic Antibody-mediated Rejection in Kidney Transplant Recipients
Study Details
Study Description
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 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 baseline, 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Arms and Interventions
| 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:
|
| 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 |
Outcome Measures
Primary Outcome Measures
- Change from baseline in eGFR at 24 months [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 Outcome Measures
- Change in Donor-specific anti-HLA antibodies (DSA) [baseline and up to 36 months]
Change in DSA from baseline based on luminex assessments every 12 months
- Incidence of adverse and serious events related to TCZ treatment [up to 25 months]
Assessments of incidence of any side effects including infectious complications associated with TCZ therapy
- Histologic changes in protocol biopsy [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 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
- Changes in proteinuria [baseline and up to 36 months]
Assessed by urine albumin creatinine ratio (UACR) at baseline and every 12 months
- Renal function assessed by measured GFR (mGFR) [baseline and up to 36 months]
Changes from baseline in renal function as assessed by mGFR using iohexol clearance
- Renal function assessed by eGFR [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)
- Patient survival [up to 36 months]
Incidence of patient survival at 12, 24 and 36 months after start of treatment
- Death-censored graft survival [up to 36 months]
Incidence of death-censored graft survival at 12, 24 and 36 months after start of treatment
- Possible change in experienced transplant-specific well-being and symptom burden [upto 36 months]
Assessed using a validated self-reported questionnaires at baseline and every 12 months
- Possible change in experienced perceived threat of the risk of graft rejection [upto 36 months]
Assessed using a validated self-reported questionnaires at baseline and every 12 months
- Possible change in adherence to immunosuppressive medications [upto 36 months]
Assessed using a validated self-reported questionnaires at baseline and every 12 months
Eligibility Criteria
Criteria
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 12 months post-transplantation at randomization
-
Biopsy-proven diagnosis of cAMR according to the Banff 2017 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:
-
Inability to tolerate any of the SOC treatment- tacrolimus, mycophenolate acid (MPA) or prednisolone
-
Recipient of multi-organ transplants
-
De novo or recurrent renal disease that, in the Investigator's opinion, could adversely influence the current allograft
-
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
-
History of tuberculosis (TB)
-
Active TB or latent TB (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
-
Active 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, reluctance or language difficulties that result in difficulty 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Transplant Center, Sahlgrenska University Hospital | Gothenburg | Vastra Gotaland Regioin | Sweden | |
| 2 | Karolinksa University Hospital | Stockholm | Sweden | SE-141 86 | |
| 3 | Uppsala University Hospital | Uppsala | Sweden | 751 85 |
Sponsors and Collaborators
- Vastra Gotaland Region
- Karolinska University Hospital
- Uppsala University Hospital
- The Swedish Research Council
Investigators
- Principal Investigator: Seema Baid-Agrawal, MD, Transplant Center, Sahlgrenska University Hospital, Gothenburg, Sweden
- Principal Investigator: Lars Wennberg, MD, PhD, Transplant Center, Karolinska University Hospital, Stockholm, Sweden
- Principal Investigator: Tomas Lorant, MD, PhD, Transplant Center, Uppsala University Hospital, Uppsala, Sweden
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2019-004302-10