A Phase II Trial to Evaluate the Safety and Efficacy of clazakizumab for the desensitisation of highly sensitized patients on the deceased donor kidney transplant waiting list
- Conditions
- End stage kidney diseaseRenal and Urogenital - Kidney disease
- Registration Number
- ACTRN12624000567527
- Lead Sponsor
- Royal Melbourne Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot yet recruiting
- Sex
- All
- Target Recruitment
- 10
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).
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method In each subject, the number and proportion of HLA antibodies that have a fall in MFI of greater than 50% or fall to MFI less than 1500<br>[One Lambda single antigen bead luminex testing During treatment at baseline and 2, 4, 6, 8, 10, 12 (primary timepoint) months]
- Secondary Outcome Measures
Name Time Method