Clazakizumab in Highly-HLA Sensitized Patients Awaiting Renal Transplant

• Status: Active, not recruiting
• Trial end date: 2023-12-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Stanley Jordan, MD

Criteria

Inclusion Criteria:

1. Age 15-75 years at the time of screening.

2. HS patients (cPRA≥50%) awaiting DD or LD kidney transplant on the UNOS list.

3. Previous history of pregnancies, blood transfusion and/or renal transplant.

4. Subject/Parent/Guardian must be willing to participate fully with study requirements.

5. Subject/Parent/Guardian must be able to understand and provide informed consent.

6. Pneumococcal vaccinated

7. Negative Tuberculin (ppd) placement result or negative Quantiferon TB gold results

Exclusion Criteria:

1. Multi-organ transplant (e.g. kidney and pancreas)

2. Intolerability to clazakizumab or other IL-6 inhibitor therapies

3. Lactating or pregnant females.

4. Women of child-bearing age and male partners of 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.

5. HIV-positive subjects.

6. Subjects who test positive for HBV by HBVeAg/DNA or HCV infection [positive Anti-HCV (EIA) and confirmatory HCV RIBA].

7. Subjects with latent or active TB. Subjects must have negative Quantiferon TB gold test result.

8. Recent recipients of any licensed or investigational live attenuated vaccine(s) within two months of the screening visit

9. A significantly abnormal general serum screening lab result defined as a ANC <2000, platelet count < 100 X 103/ml, an SGOT or SGPT > 1.5X upper limit normal.

10. Individuals deemed unable to comply with the protocol.

11. 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.

12. Use of investigational agents within 4 weeks of participation.

13. History or active Inflammatory Bowel Disease or Diverticular Disease or gastrointestinal perforation

14. Recent infection (within past 6 weeks of screening) requiring any antibiotic use (oral, parenteral or topical).

15. 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