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Kidney Failure, ChronicPhase 1/2NCT03380962

Clazakizumab in Highly-HLA Sensitized Patients Awaiting Renal Transplant

A Phase 1/2 study testing Clazakizumab in people with Kidney Failure, Chronic and End-Stage Renal Disease, run by Stanley Jordan, MD at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 15 to 75 years
What is being tested?
Clazakizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
27 Feb 2018to 30 Aug 2025
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 15 to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Age 15-75 years at the time of screening.
  • HS patients (cPRA≥50%) awaiting deceased donor (DD) or living donor (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 tuberculosis (TB) gold results

Who cannot join

  • Multi-organ transplant (e.g. kidney and pancreas)
  • Intolerability to clazakizumab or other interleukin-6 (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 hepatitis B virus (HBV) by HBVeAg/DNA or hepatitis C virus (HCV) infection [positive Anti-HCV (EIA) and confirmatory HCV RIBA].
Show all 15Show fewer
  • Subjects with latent or active tuberculosis. 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 absolute neutrophil count (ANC) <2000, platelet count < 100 X 10^3/ml, an aspartate aminotransferase (AST) or alanine transaminase (ALT) > 1.5X upper limit normal.
  • Individuals deemed unable to comply with the protocol.
  • Subjects with active Cytomegalovirus (CMV) or Epstein-Barr virus (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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Norko Ammerman

    Los Angeles, California, 90048

Other trials in United States

About this study

Official title: A Phase I/II Trial to Evaluate the Safety and Tolerability of Clazakizumab (Anti-IL-6 Monoclonal) to Eliminate Donor Specific HLA Antibodies (DSAs) and Improve Transplant Rates in Highly-HLA Sensitized Patients Awaiting Renal Transplant

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.

Read the detailed description

This is a single center, Phase I/II, open label single-arm exploratory study. The trial will primarily examine the safety and tolerability of clazakizumab given after consented and eligible patients begin desensitization therapy to achieve HLAi renal transplantation at Cedars-Sinai Medical Center. 20 subjects (ages 15 to 75) who are highly-HLA sensitized (HS) as determined by the calculated Panel Reactive Antibody (cPRA) ≥50% and are eligible for desensitization will be evaluated. All patients will be accrued from the renal transplant program at Cedars-Sinai Medical Center. Once desensitization begins, anti-HLA antibodies will be assessed which are associated with antibody-mediated rejection (ABMR) and/or graft loss. HLA antibodies will be detected using solid phase assay systems currently utilized at the Cedars-Sinai Medical Center HLA Laboratory. These anti-HLA antibodies may result naturally or from previous pregnancy, transfusions, or prior transplants. Patients treated with clazakizumab x 6 doses for desensitization will have blood sampling for HLA antibodies, and other monitoring blood samples as well as immunologic studies as outlined. If patients receive an HLAi transplant during the study, participants will receive the standard post-transplant immunosuppressive protocol, and clazakizumab 25 mg subcutaneous (SC) Q4 weeks X 6 doses with immune monitoring as indicated.

Immune monitoring in blood samples for regulatory T-cell (Treg), T follicular helper (Tfh), Th17 and B-cell subsets as well as interleukin-6 (IL-6) and C-reactive protein (CRP) monitoring will be carried out at the Cedars-Sinai Transplant Immunology Laboratory.

Patients identified as study participants will be HS and listed for HLAi renal transplantation at Cedars-Sinai Medical Center. Cedars-Sinai is a major U.S. desensitization center and performs ~80 HLAi renal transplants per-year. ~ 100 new HS patients are referred to Cedars-Sinai each year as potential candidates for desensitization. Eligible patients entering the study will initially receive plasmapheresis (PLEX; 5-7 sessions) + intravenous immunoglobulin (IVIG) and receive clazakizumab 25 mg SC one week post-IVIG. If no safety/tolerability/efficacy issues are observed after the initial dose, patients will receive 5 additional injections Q4 weeks. If patients receive an HLAi transplant, clazakizumab will be continued for 6 months (M) post- transplant at 25mg SC Q4weeks for 6 doses (starting at Day 5 post-transplant). A protocol biopsy will be performed at 6M post-transplant to assess the allograft for evidence of ABMR, including C4d staining and TG using Banff 2015 criteria. 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. In the event a patient does not show improvement after receiving 6 doses of clazakizumab, no further treatment will be given and the patient will return at Day 365 for a final study visit. All subjects will be evaluated on an intent-to-treat basis. The subject accrual rate will be limited to no more than 1-2 subjects per month in the initial three months to assure safety to all subjects. Repeat laboratories will be performed at the completion of clazakizumab therapy to determine effect on levels and correlation with any potential events.

The subjects will be followed to determine if the use of clazakizumab for desensitization in this high risk transplant population is safe and without infectious risks. In addition, the investigators will determine the effects of clazakizumab treatment on HLA antibodies in efforts to improve access to HLAi transplants for these individuals. The investigators have previously reported acceptance criteria for HLAi kidney transplants. Renal biopsy assessments will be performed at 6M (per protocol) and 12M (for those who received 12 doses of therapy). The investigators will assess the transplanted patients to determine the number who sustain a viable and functioning kidney allograft as well. All subjects will be evaluated on an intent-to-treat basis. The subject accrual rate will be limited to no more than 1-2 subjects per month in the initial three months to assure safety to all subjects.

Being tested
Clazakizumab
Keywords
Donor-Specific Anti-HLA Antibodies, Kidney Transplantation, Donor Specific Antibody
Medical subject headings
Kidney Failure, Chronic, Rejection, Psychology

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ClazakizumabDrug

    Also called Anti-IL-6 monoclonal

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

Study groups in NCT03380962
Study groupRoleWhat they receive
ClazakizumabExperimentalAll 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 Principal Investigator (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.
Receives: Drug: Clazakizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Treatment Related Adverse Effects of Clazakizumab Therapy (18 Month Period)

    Assessments of any side effects associated with clazakizumab administration. Adverse event (AE) data was collected while patients received clazakizumab monthly. Patients received up to 6 monthly doses pre-transplantation (6 months). If patients were transplanted during the study, they then received 12 monthly doses of clazakizumab post-transplant (12 months). Patients were therefore monitored for safety data for up to 6 months prior to and 12 months post-transplantation (18 months in total).

    Measured: 18 months (6 months pre-transplant and 12 months post-transplant)

Secondary outcomes (4)
  1. Change in Donor Specific Antibodies (Mean Fluorescence Intensity: MFI), Class I Antibodies, Post-transplant

    Assessment of human leukocyte antigen (HLA) antibodies from baseline based on luminex assessments (MFI) to 6 months post-transplant

    Measured: 6 months post-transplant

  2. Estimated Glomerular Filtration Rate (eGFR) at 12 Months Post-transplant.

    Assessment of renal function (eGFR) by collecting Serum Creatinine (md/dl) at 12 months post-transplant.

    Measured: 12 months post-transplant

  3. Number of Antibody Mediated Rejection (ABMR) Episodes

    Assessment of biopsy results to number how many episodes of ABMR occurred in transplanted patients.

    Measured: 12 months post-transplant

  4. Change in Donor Specific Antibodies (MFI), Class II Antibodies, Post-transplant

    Assessment of HLA antibodies from baseline based on luminex assessments (MFI) to 6 months post-transplant

    Measured: 6 months post-transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Dec 2017
  2. Study start27 Feb 2018
  3. Primary completion30 Aug 2025
  4. Study completion30 Aug 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Twenty enrolled study patients will receive study medication Clazakizumab (Vitaeris Inc; Vancouver Canada, BC)
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03380962
Sponsor's protocol ID
48478
Status last verified
Oct 2026
First submitted
30 Oct 2017
Last updated
30 Oct 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 28199785
  • 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.

    PubMed 37322595

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Clazakizumab in people with Kidney Failure, Chronic and End-Stage Renal Disease, run by Stanley Jordan, MD at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Treatment Related Adverse Effects of Clazakizumab Therapy (18 Month Period) (time frame: 18 months (6 months pre-transplant and 12 months post-transplant)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03380962, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2026.

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