A Phase I/II Trial to Evaluate the Safety and Tolerability of Clazakizumab (Anti-IL-6 Monoclonal) As an Agent to Eliminate Donor Specific HLA Antibodies and Improve Outcomes of Patients With Chronic & Active Antibody-Mediated Rejection Post-Kidney Transplantation

134733

Antibody mediated rejection (ABMR) is a unique, significant and often severe form of allograft rejection. This single center, phase I/II, open label single-arm exploratory study focuses on enrolling ten patients with biopsy proven chronic antibody medicated rejection and/or donor specific antibody present at time of biopsy. Patients who qualify will be receiving clazakizumab (anti-IL6 monoclonal antibody) monthly x six doses. A protocol biopsy will be performed at 6 months and if improvement is seen, patients will continue another six doses for up to 12 months. For those completing 12 doses, there will be a 12 month protocol biopsy. For those who only received six doses, the next and last study visit will be at 12 months from enrollment. Total study duration is 12 months.

2018-02-21

2024-04-16

2024-04-16

Completed

Early phase I

10

Inclusion Criteria: 1. Age 15-75 years at the time of screening. 2. Biopsy proven cABMR with TG on biopsy as defined by Banff 2015 and DSA positive at time of biopsy 3. Subject/Parent/Guardian must be able to understand and provide informed consent. 4. Pneumococcal vaccinated 5. Negative tuberculin ppd result or negative Quantiferon TB gold Exclusion Criteria: 1. Multi-organ transplant (e.g. kidney and pancreas) 2. eGFR \< 30 mL/min/1.73m2 3. Advanced Transplant Glomerulopathy (CG3) 4. Previous allergic reactions to monoclonal antibodies. 5. Lactating or pregnant females. 6. Women of child-bearing age who are not willing or able to practice FDA-approved forms of contraception during study and for 5 months after last dose. 7. HIV-positive subjects. 8. Subjects who test positive for HBV by HBVeAg/DNA or HCV infection \[positive Anti-HCV (EIA) and confirmatory HCV RIBA\]. 9. Subjects with latent or active TB. Subjects must have negative Quantiferon TB gold test result. 10. Recent recipients of any licensed or investigational live attenuated vaccine(s) within two months of the screening visit j) A significantly abnormal general serum screening lab result defined as a WBC \< 3.0 X 103/ml, a Hgb \< 8.0 g/dL, a platelet count \< 100 X 103/ml, an SGOT or SGPT \> 3X upper limit normal 11. Individuals deemed unable to comply with the protocol. 12. Subjects with active CMV or EBV infection as defined by CMV-specific serology (IgG or IgM) and confirmed by quantitative PCR with or without a compatible illness. 13. Use of investigational agents within 4 weeks of participation. 14. History or active Inflammatory Bowel Disease or Diverticular Disease or gastrointestinal perforation 15. Recent infection (within past 6 weeks of screening) requiring any antibiotic use (oral, parenteral or topical). 16. Present or previous (within 5 years) malignancy except for basal cell carcinoma, fully excised squamous cell carcinoma of the skin or non-recurrent (within 5 years) cervical carcinoma-in-situ.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'All ten patients enrolled will receive study medication (Clazakizumab, Vitaeris, Inc, Vancouver, Canada, B.C)', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 10, 'type': 'ACTUAL'}}

2024-05-17