Clazakizumab for Chronic and Active Antibody Mediated Rejection Post-Kidney Transplant

NCT03380377 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 134733
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Antibody-mediated Rejection; Kidney Transplant; Complications; Transplant Glomerulopathy; Transplant Glomerulopathy - Late Form; Transplant Glomerulopathy - Early Form; Kidney Transplant Rejection

Keywords

kidney transplant; Chronic antibody mediated rejection; donor specific antibody

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Donor Specific Antibody (DSA) Elimination or Reduction Based on Luminex HLA Testing

  Did clazakizumab eliminate or weaken donor specific antibody (DSA) mean fluorescence intensity (MFI) intensities? HLA antibodies were detected by the single antigen bead-based assay (One lambda, Los Angeles, CA). Donor HLA-specific antibodies were assessed throughout clazakizumab treatment for the first year. Detection of DSAs were only reported with MFI \>2500.

  12 months

• Number of Participants With Stabilization of Clinical Features of cABMR Via BANFF Biopsy Grading Criteria.

  Does clazakizumab help stabilize pathologic features of antibody mediated rejection at 6 month protocol biopsies? Protocol kidney allograft biopsies were performed at 6 months and compared to the baseline biopsy which was assessed for study inclusion. Biopsy specimens were analyzed according to Banff 2017 classification.

  6 months

Secondary Outcomes (2)

• Stabilization in Estimated Glomerular Filtration Rate (eGFR)

  12 months

• Incidence of Treatment-related Adverse Events

  12 months

Study Arms (1)

Clazakizumab (Anti-IL-6 Monoclonal)

EXPERIMENTAL

All ten patients will be receiving clazakizumab (Anti-IL-6 Monoclonal) monthly for six months. Then patients will be scheduled for six month protocol biopsy. If biopsy and all clinical labs show benefit or stability (up to PI discretion), patients will continue receiving clazakizumab monthly for another six months. All patients completing twelve doses of clazakizumab will be scheduled for a twelve month protocol biopsy and last study visit. If at the 6 month protocol biopsy, no improvement was seen, PI will have patient come for their last study visit on month 12 post enrollment.

Drug: Clazakizumab

Interventions

Clazakizumab DRUG

Clazakizumab 25 mg subcutaneous monthly x 6 doses (or max of 12 doses) will be given to patients who are enrolled in this clinical trial.

Clazakizumab (Anti-IL-6 Monoclonal)

Eligibility Criteria

• Age: 15 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 15-75 years at the time of screening.
• Biopsy proven cABMR with TG on biopsy as defined by Banff 2015 and DSA positive at time of biopsy
• Subject/Parent/Guardian must be able to understand and provide informed consent.
• Pneumococcal vaccinated
• Negative tuberculin ppd result or negative Quantiferon TB gold

You may not qualify if:

• Multi-organ transplant (e.g. kidney and pancreas)
• eGFR \< 30 mL/min/1.73m2
• Advanced Transplant Glomerulopathy (CG3)
• Previous allergic reactions to monoclonal antibodies.
• Lactating or pregnant females.
• 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.
• HIV-positive subjects.
• Subjects who test positive for HBV by HBVeAg/DNA or HCV infection \[positive Anti-HCV (EIA) and confirmatory HCV RIBA\].
• Subjects with latent or active TB. Subjects must have negative Quantiferon TB gold test result.
• 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
• Individuals deemed unable to comply with the protocol.
• 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.
• Use of investigational agents within 4 weeks of participation.
• History or active Inflammatory Bowel Disease or Diverticular Disease or gastrointestinal perforation
• Recent infection (within past 6 weeks of screening) requiring any antibiotic use (oral, parenteral or topical).

Sponsors & Collaborators

• Stanley Jordan, MD: lead

Study Sites (1)

Norko Ammerman

Los Angeles, California, 90048, United States

Location

Related Publications (1)

• Choi J, Aubert O, Vo A, Loupy A, Haas M, Puliyanda D, Kim I, Louie S, Kang A, Peng A, Kahwaji J, Reinsmoen N, Toyoda M, Jordan SC. Assessment of Tocilizumab (Anti-Interleukin-6 Receptor Monoclonal) as a Potential Treatment for Chronic Antibody-Mediated Rejection and Transplant Glomerulopathy in HLA-Sensitized Renal Allograft Recipients. Am J Transplant. 2017 Sep;17(9):2381-2389. doi: 10.1111/ajt.14228. Epub 2017 Mar 10.

  PMID: 28199785 BACKGROUND

MeSH Terms

Interventions

clazakizumab

Limitations and Caveats

Our phase 2 trial has several limitations, including the lack of a randomized controlled design with a placebo-treated control arm, a small sample size and variability among the participants at baseline

Results Point of Contact

• Title: Stan Jordan, MD
• Organization: Cedars Sinai Medical Center

stan.jordan@cshs.org

3104232641

Study Officials

• Stanley Jordan, MD

  Cedars-Sinai Medical Center Comprehensive Transplant Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of the Kidney Transplant Program

Model Details: All ten patients enrolled will receive study medication (Clazakizumab, Vitaeris, Inc, Vancouver, Canada, B.C)

Study Record Dates

• First Submitted: August 3, 2017
• First Posted: December 21, 2017
• Study Start: February 21, 2018
• Primary Completion: April 16, 2024
• Study Completion: April 16, 2024
• Last Updated: May 6, 2025
• Results First Posted: May 6, 2025

Record last verified: 2025-04

Locations

US (1)