Clazakizumab in Highly-HLA Sensitized Patients Awaiting Renal Transplant

NCT03380962 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 48478
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Kidney Failure, Chronic; End-Stage Renal Disease; Transplant Glomerulopathy; Transplant;Failure,Kidney; Kidney Transplant Failure and Rejection; Antibody-mediated Rejection; Kidney Transplant; Complications

Keywords

Donor-Specific Anti-HLA Antibodies; Kidney Transplantation; Donor Specific Antibody

Outcome Measures

Primary Outcomes (2)

• Change in donor specific antibodies

  Assessment of HLA antibodies from baseline based on luminex assessments at multiple time points

  Up to 21 months

• Incidence of treatment related adverse effects of clazakizumab therapy

  Assessments of any side effects associated with clazakizumab administration and risk for infectious complications associated with clazakizumab therapy for desensitization of HS patients awaiting renal HLAi transplantation

  Up to 21 months

Secondary Outcomes (2)

• Change in Serum Creatinine

  Up to 21 months

• Incidence of ABMR episodes

  Up to 12 months post-transplant

Study Arms (1)

Clazakizumab

EXPERIMENTAL

All twenty patients will receive clazakizumab monthly. Patients will receive up to 6 doses pre-transplantation. If patients are transplanted during the study, they will then receive 6 doses of clazakizumab (monthly) and a 6 month protocol biopsy will be performed. Based on the biopsy results and clinical labs PI will determine if patients should continue monthly doses for up to another 6 doses and day 330 post-transplantation. Patients who received 12 post-transplant doses of clazakizumab will then undergo a 12 month protocol biopsy.

Drug: Clazakizumab

Interventions

Clazakizumab DRUG

All patients will receive clazakizumab 25 mg subcutaneous injections (monthly) for a maximum of 18 injections.

Also known as: Anti-IL-6 monoclonal

Clazakizumab

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.
• HS patients (cPRA≥50%) awaiting DD or LD kidney transplant on the UNOS list.
• Previous history of pregnancies, blood transfusion and/or renal transplant.
• Subject/Parent/Guardian must be willing to participate fully with study requirements.
• Subject/Parent/Guardian must be able to understand and provide informed consent.
• Pneumococcal vaccinated
• Negative Tuberculin (ppd) placement result or negative Quantiferon TB gold results

You may not qualify if:

• Multi-organ transplant (e.g. kidney and pancreas)
• Intolerability to clazakizumab or other IL-6 inhibitor therapies
• Lactating or pregnant females.
• 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.
• 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
• 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.
• 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).
• 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

Sponsors & Collaborators

• Stanley Jordan, MD: lead

Study Sites (1)

Norko Ammerman

Los Angeles, California, 90048, United States

Location

Related Publications (2)

• 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

• Fernando SC, Polkinghorne KR, Lim WH, Mulley WR. Early Versus Late Acute AMR in Kidney Transplant Recipients-A Comparison of Treatment Approaches and Outcomes From the ANZDATA Registry. Transplantation. 2023 Nov 1;107(11):2424-2432. doi: 10.1097/TP.0000000000004700. Epub 2023 Jun 16.

  PMID: 37322595 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic; Rejection, Psychology

Interventions

clazakizumab

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Social Behavior; Behavior

Study Officials

• Stanley Jordan, MD

  Cedars-Sinai Medical Center Comprehensive Transplant Center

  PRINCIPAL INVESTIGATOR

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: Twenty enrolled study patients will receive study medication Clazakizumab (Vitaeris Inc; Vancouver Canada, BC)

Study Record Dates

• First Submitted: October 30, 2017
• First Posted: December 21, 2017
• Study Start: February 27, 2018
• Primary Completion: August 30, 2025
• Study Completion: August 30, 2025
• Last Updated: March 24, 2025

Record last verified: 2025-03

Locations

US (1)