Clinical Trials Logo

Clinical Trial Summary

Patients who have had a previous allograft failure represent a major problem for transplant centers as they are highly-human leukocyte antigen (HLA) sensitized and unlikely to receive another transplant without significant desensitization. This single center, phase I/II, open label single-arm exploratory study focuses on enrolling twenty patients (ages 15-75) who will begin desensitization therapy to achieve HLA incompatible (HLAi) renal transplantation. Patients who qualify will receive up to 6 doses of clazakizumab 25 mg monthly pre-transplantation. If patients receive an HLAi transplant during the study, the participants will continue to receive another 6 monthly doses of clazakizumab 25 mg, followed by a 6 month protocol biopsy. Patients will continue another 6 doses over 6 months if improvements are seen after the 6th dose of clazakizumab. Patients who develop evidence of persistent allograft dysfunction may have non-protocol biopsies for cause. Patients who receive 12 doses of clazakizumab post-transplant will receive a 12M protocol biopsy.


Clinical Trial Description

This is a single center, Phase I/II, open label single-arm exploratory study. The trial will primarily examine the safety and tolerability of clazakizumab given after consented and eligible patients begin desensitization therapy to achieve HLAi renal transplantation at Cedars-Sinai Medical Center. 20 subjects (ages 15 to 75) who are highly-HLA sensitized (HS) as determined by the cPRA ≥50% and are eligible for desensitization will be evaluated. All patients will be accrued from the renal transplant program at Cedars-Sinai Medical Center. Once desensitization begins, anti-HLA antibodies will be assessed which are associated with ABMR and/or graft loss. HLA antibodies will be detected using solid phase assay systems currently utilized at the Cedars-Sinai Medical Center HLA Laboratory. These anti-HLA antibodies may result naturally or from previous pregnancy, transfusions, or prior transplants. Patients treated with clazakizumab x 6 doses for desensitization will have blood sampling for HLA antibodies, and other monitoring blood samples as well as immunologic studies as outlined. If patients receive an HLAi transplant during the study, participants will receive the standard post-transplant immunosuppressive protocol, and clazakizumab 25 mg SC Q4W X 6 doses with immune monitoring as indicated. Immune monitoring in blood samples for Treg, Tfh, Th17 and B-cell subsets as well as IL-6 and CRP monitoring will be carried out at the Cedars-Sinai Transplant Immunology Laboratory. Patients identified as study participants will be HS and listed for HLAi renal transplantation at Cedars-Sinai Medical Center. Cedars-Sinai is a major U.S. desensitization center and performs ~80 HLAi renal transplants per-year. ~ 100 new HS patients are referred to Cedars-Sinai each year as potential candidates for desensitization. Eligible patients entering the study will initially receive PLEX (5-7 sessions) + IVIG and receive clazakizumab 25 mg SC one week post-IVIG. If no safety/tolerability/efficacy issues are observed after the initial dose, patients will receive 5 additional injections Q4W. If patients receive an HLAi transplant, clazakizumab will be continued for 6M post- transplant at 25mg SC Q4W for 6 doses (starting at Day 5 post-transplant). A protocol biopsy will be performed at 6M post-transplant to assess the allograft for evidence of ABMR, including C4d staining and TG using Banff 2015 criteria. Patients will continue another 6 doses over 6 months if improvements are seen after the 6th dose of clazakizumab. Patients who develop evidence of persistent allograft dysfunction may have non-protocol biopsies for cause. Patients who receive 12 doses of clazakizumab post-transplant will receive a 12M protocol biopsy. In the event a patient does not show improvement after receiving 6 doses of clazakizumab, no further treatment will be given and the patient will return at Day 365 for a final study visit. All subjects will be evaluated on an intent-to-treat basis. The subject accrual rate will be limited to no more than 1-2 subjects per month in the initial three months to assure safety to all subjects. Repeat laboratories will be performed at the completion of clazakizumab therapy to determine effect on levels and correlation with any potential events. The subjects will be followed to determine if the use of clazakizumab for desensitization in this high risk transplant population is safe and without infectious risks. In addition, the investigators will determine the effects of clazakizumab treatment on HLA antibodies in efforts to improve access to HLAi transplants for these individuals. The investigators have previously reported acceptance criteria for HLAi kidney transplants. Renal biopsy assessments will be performed at 6M (per protocol) and 12M (for those who received 12 doses of therapy). The investigators will assess the transplanted patients to determine the number who sustain a viable and functioning kidney allograft as well. All subjects will be evaluated on an intent-to-treat basis. The subject accrual rate will be limited to no more than 1-2 subjects per month in the initial three months to assure safety to all subjects. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03380962
Study type Interventional
Source Cedars-Sinai Medical Center
Contact
Status Active, not recruiting
Phase Phase 1/Phase 2
Start date February 27, 2018
Completion date July 30, 2025

See also
  Status Clinical Trial Phase
Completed NCT03246984 - VALUE- Vascular Access Laminate eUropean Experience. A Post Market Surveillance Study to Assess the Safety and Effectiveness of VasQ N/A
Not yet recruiting NCT05968391 - Acetoacetate and Acetate Metabolism in Patients With Chronic Kidney Failure.(RENO-TEP)
Completed NCT02922361 - Spending and Outcomes for Complex Medicare Advantage Patients
Completed NCT02235571 - iChoose Decision Kidney Aid for End-Stage Renal Disease Patients N/A
Completed NCT01922843 - A Phase 2 Study of an Oral Vitamin D Compound (DP001) in Secondary Hyperparathyroidism in Patients on Hemodialysis Phase 2
Completed NCT01930396 - Use of Tinzaparin for Anticoagulation in Hemodialysis Phase 4
Completed NCT01933789 - Improving Communication About Serious Illness N/A
Not yet recruiting NCT01674660 - Factors Associated With Interdialytic Blood Pressure Variability in Maintenance Hemodialysis Patients N/A
Not yet recruiting NCT01157260 - The Effects of AST-120 on Endothelial Dysfunction in Patients With Chronic Kidney Disease Phase 4
Completed NCT01209403 - Insulin-like Growth Factor (IGF-I) in Hemodialysis Patients Phase 4
Completed NCT00753116 - Renal Denervation in End Stage Renal Disease Patients With Refractory Hypertension Phase 1
Recruiting NCT00532688 - N-Acetylcysteine in Heart Failure With Coexistent Chronic Renal Failure Phase 2/Phase 3
Completed NCT00534144 - Comparison Between Effects of Two Iron Preparations on Protein in the Urine Phase 1
Completed NCT00528788 - How Vitamin D Analogues Affect Endothelial Cells in Patients on Dialysis Phase 4
Completed NCT00382044 - Audit of the Effect of Changing From IV to SC Administration of ESA's in Haemodialysis Patients N/A
Completed NCT00226902 - Vascular Reactivity in Kidney Disease Patients N/A
Recruiting NCT00235287 - Pulse Wave Velocity, Pulse Wave Morphology and Blocking of the Reninangiotensin System in Patients With Chronic Kidney Disease Phase 4
Completed NCT00224081 - DRIVE Trial (Dialysis Patients' Response to Intravenous [IV] Iron With Elevated Ferritin) Phase 4
Completed NCT00071214 - Study to Evaluate the Effectiveness of StaphVAX in Adults on Hemodialysis Phase 3
Completed NCT00049907 - Cardiac and Renal Disease Study (CARDS) N/A