None listed
Conditions
Brief summary
Kidney transplantation improves the survival and quality of life of people with end-stage kidney disease (ESKD) compared to remaining on dialysis. One of the major barriers preventing some people with ESKD from receiving a transplant is the presence of antibodies against a broad range of HLA antigens found in the community. Transplantation in the presence of antibodies directed against the HLA type of the donor (donor specific antibody, DSA) is associated with an increased risk of antibody-mediated rejection, development of transplant glomerulopathy and graft loss. To minimise this risk, many deceased donor kidney transplant allocation systems allow potential recipients to avoid donors with HLA antigens to which the recipient has detectable antibodies. There is therefore an unmet need for a strategy to reduce the number of HLA-specific antibodies in these highly sensitised patients. This study will specifically investigate whether Clazakizumab is effective at reducing HLA antibody levels, whether this allows some HLA types to be removed from the list deemed unacceptable and whether this increases the chance of transplantation. It will also study the safety of this intervention and the outcomes of the transplants performed.
Interventions
Clazakizumab 12.5mg subcutaneously every 4 weeks for up to 52 weeks, unless the individual receives a kidney transplant during the period of treatment. If they receive a transplant then Clazakizumab 12.5mg subcutaneously every 4 weeks is continued if they have ever had an antibody against donor HLA, otherwise it is stopped at the time of transplant. If it is continued after transplant then it is stopped 3 months after transplant if no donor specific antibody is detectable and there is no antibod
Clazakizumab 12.5mg subcutaneously every 4 weeks for up to 52 weeks, unless the individual receives a kidney transplant during the period of treatment. If they receive a transplant then Clazakizumab 12.5mg subcutaneously every 4 weeks is continued if they have ever had an antibody against donor HLA, otherwise it is stopped at the time of transplant. If it is continued after transplant then it is stopped 3 months after transplant if no donor specific antibody is detectable and there is no antibody-mediated rejection on a surveillance biopsy. If clazakizumab is not stopped at 3 months then it is stopped at 6 months after transplant.
Sponsors
Royal Melbourne Hospital
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-70 years at the time of screening. 2. Highly sensitized: a. with a cPRA of greater than 98% based on their current unacceptable HLA antigens on the transplant waiting list. b. Must remain highly sensitized with a cPRA greater than 95% after altering unacceptable HLA antigens to only include those to which they have current antibodies detected by Luminex screening with an MFI greater than 1500 or lower if it is an antibody against a repeat HLA mismatch from a previous transplant, if it appears likely that an anti-HLA antibody is binding multiple different Luminex beads leading to an apparent lowering of the MFI or if a previous surrogate flow cytometric crossmatch was positive due to that antibody. 3. Must have end-stage kidney disease and currently be active on the deceased donor kidney transplant waiting list for greater than 12 months. 4. Written informed consent obtained from subject (or legally acceptable representative).
Exclusion criteria
1. Participant is unable or unwilling to comply with study procedures in the opinion of the Investigator. 2. Requiring multi-organ transplant. 3. Pregnant, breastfeeding, or unwillingness to practice highly effective birth control during the study and for 5 months after last dose of study medication. 4. History of anaphylaxis. 5. Abnormal liver function test (LFTs) (alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/bilirubin greater than 1.5 times the upper limit of normal) at screening or other significant liver disease. 6. Latent or active tuberculosis: a. Chest X-ray (CXR) in the past 6 months showing evidence of latent or active tuberculosis. If CXR is not available, it must be performed at screening. and/or b. Positive QuantiFERON-TB Gold test at screening. 7. Human Immunodeficiency Virus (HIV) positive at screening. 8. Presence of hepatitis B surface antigen (HBsAg) at screening 9. Hepatitis C virus (HCV) RNA positive at screening. 10. History of inflammatory bowel disease (except fully excised and recovered from the surgery for ulcerative colitis), clinically significant diverticular disease (unless fully excised and recovered from the surgery) or history of GI perforation. 11. Neutropenia (less than 1,000/mm3) or thrombocytopenia (less than 100,000/mm3) at screening. 12. Active infections requiring systemic (IV or oral) antimicrobial agents. 13. History or current opportunistic infection, including (but not limited to) the following: a nontuberculous mycobacterial infection, pneumocystis, aspergillosis, and toxoplasmosis. 14. Active viral infections such as CMV, EBV, JCV, and polyoma BK. 15. Current participation in an investigational drug trial. 16. Administration of a live vaccine within 6 weeks of screening, including but not limited to the following: a. Adenovirus [Adenovirus vaccine live oral type 7] b. Varicella [Varivax] c. Hepatitis A [VAQTA] d. Rotavirus [Rotashield] e. Yellow fever [Y-F-Vax] f. Measles and mumps live virus vaccine g. Measles, mumps, and rubella vaccine [MMR-II] h. Sabin oral polio vaccine i. Rabies vaccines [IMOVAX Rabies I.D., RabAvert]) j. Present or previous (within 5 years) malignancy except for basal cell carcinoma, fully excised squamous cell carcinoma of the skin, non-recurrent (within 5 years) cervical carcinoma in-situ, DCIS following completion of therapy or T1a renal cell carcinoma. 17. Presence of a condition or abnormality (i.e., clinically significant endocrine, autoimmune, metabolic, neurological, psychiatric/psychological, renal, gastrointestinal, hepatic, and hematological or any other system abnormalities that are uncontrolled with standard treatment) that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
Outcome results
None listed