Clazakizumab in Highly-HLA Sensitized Patients Awaiting Renal Transplant

March 20, 2025 updated by: Stanley Jordan, MD

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 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 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 SC Q4W X 6 doses with immune monitoring as indicated.

Immune monitoring in blood samples for Treg, Tfh, Th17 and B-cell subsets as well as IL-6 and 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 PLEX (5-7 sessions) + 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 Q4W. If patients receive an HLAi transplant, clazakizumab will be continued for 6M post- transplant at 25mg SC Q4W 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Norko Ammerman

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

15 years to 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Clazakizumab
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
All patients will receive clazakizumab 25 mg subcutaneous injections (monthly) for a maximum of 18 injections.
Other Names:
  • Anti-IL-6 monoclonal

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in donor specific antibodies
Time Frame: Up to 21 months
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
Time Frame: Up to 21 months
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Serum Creatinine
Time Frame: Up to 21 months
Assessment of renal function by collecting Serum Creatinine (md/dl) at multiple time points
Up to 21 months
Incidence of ABMR episodes
Time Frame: Up to 12 months post-transplant
Assessment of protocol biopsy results
Up to 12 months post-transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Stanley Jordan, MD

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Stanley Jordan, MD, Cedars-Sinai Medical Center Comprehensive Transplant Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 27, 2018

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 30, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 30, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 30, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 20, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 21, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 20, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 48478

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Kidney Failure, Chronic

Clinical Trials on Clazakizumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings