A Phase 1/2 interventional study of Clazakizumab in Antibody-mediated Rejection, Kidney Transplant; Complications and Transplant Glomerulopathy, sponsored by Stanley Jordan, MD. Completed at 1 site in United States. Open to participants aged 15 Years to 75 Years. Per ClinicalTrials.gov, last updated 2025-05-06.
Sponsored by Stanley Jordan, MD · Phase 1/2, Interventional, and Treatment
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.
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 the diagnosis of cABMR in 10 subjects (15-75yrs) who exhibit DSAs to their donor. Patients entered will also have been diagnosed with cABMR + TG post-transplant based on Banff 2015 criteria. Patients are required to have a eGFR > 30 mL/min/1.73m2 as calculated by the MDRD equation (Schwartz equation will be used to estimate CrCl for patients under 18 years of age) at entry. All patients will be recruited from the renal transplant program at Cedars-Sinai Medical Center. Once cABMR is diagnosed, donor-specific anti-HLA antibodies will be assessed (DSA) which are associated with cABMR and/or graft loss. DSA will be detected using solid phase assay systems currently utilized at the Cedars-Sinai Medical Center HLA Laboratory (Dr. Xiaohai Zhang Director, Phone: 310-423-4979)41. These anti-HLA antibodies may result naturally or from previous pregnancy, transfusions, or prior transplants. Patients treated with clazakizumab for cABMR will have labs for DSAs, and other monitoring labs as well as immunologic studies as outlined. In addition to the standard post-transplant immunosuppressive protocol, patients with cABMR will receive clazakizumab 25mg SC given every 4 weeks (30 days) for a total of 6 doses. If no safety/tolerability/efficacy issues are observed after the initial dose, patients will continue the protocol as outlined. A protocol biopsy will be performed after the 6th and after the 12th doses of clazakizumab to assess the allograft for evidence of cABMR/ABMR, including C4d staining and TG using Banff 2015 criteria14. Banff scoring will be compared between the index and protocol biopsy after cessation of therapy. Patients who have evidence of persistent allograft dysfunction may have non-protocol biopsies for cause. After completion of the clazakizumab therapy, patients will be followed up to assess allograft function and ABMR episodes as well as DSAs. The protocol is summarized in figure 14 below. Monitoring of Treg, Th17, Tfh and plasmablast as well as IL-6, and CRP levels will be performed in the Transplant Immunology Lab at Cedars-Sinai Medical Center at select time points (Dr. Mieko Toyoda Director, Phone: 310-423-8282). confirmation) they will continue monthly clazakizumab for an additional 6 months and will have a second biopsy at 12 month protocol. Immunologic and viral monitoring labs will be performed as indicated.
The subjects will be followed to determine if the use of clazakizumab for treatment of cABMR in this high-risk transplant population is safe and without infectious risks. In addition, the investigators will determine the effects of clazakizumab treatment on renal biopsy assessments performed at 6 months. Assessments of renal function, donor specific antibody, and Banff 2015 biopsy scores will be evaluated at that time. If improvement or stabilization observed, clazakizumab will be resumed monthly x 6 doses (starting day 180 to day 330) and last study visit will be day 365 with biopsy. Study investigators will assess the transplanted patients to determine the number who sustain a viable and functioning kidney allograft as well. 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.
Long term dosing option at conclusion of 12 months (after Study Day 365 visit) will be available for those patients who complete the 12 month protocol. Patients may continue to receive clazakizumab 25 mg subQ every 8 weeks long term, per PI discretion.
Stanley Jordan, MD is the lead sponsor of 4 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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.
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.
Time frame: 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.
Time frame: 6 months
Stabilization in Estimated Glomerular Filtration Rate (eGFR)
Serum creatinine (mg/dl) collected to calculate eGFR
Time frame: 12 months
Incidence of Treatment-related Adverse Events
Adverse event monitoring in our patient population; did patients have treatment related adverse events and if so, how many events
Time frame: 12 months
| Milestone | Clazakizumab (Anti-IL-6 Monoclonal) |
|---|---|
| Started | 10 |
| Completed | 8 |
| Not completed | 2 |
| Withdrew: Physician decision | 1 |
| Withdrew: Withdrawal by subject | 1 |
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.
| Participants | Clazakizumab (Anti-IL-6 Monoclonal) |
|---|---|
| Number of Participants With Donor Specific Antibody (DSA) Elimination or Reduction Based on Luminex HLA Testing | 7 |
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.
| Participants | Clazakizumab (Anti-IL-6 Monoclonal) |
|---|---|
| Number of Participants With Stabilization of Clinical Features of cABMR Via BANFF Biopsy Grading Criteria. | 9 |
Serum creatinine (mg/dl) collected to calculate eGFR
| ml/min/1.73m2 | Clazakizumab (Anti-IL-6 Monoclonal) |
|---|---|
| Stabilization in Estimated Glomerular Filtration Rate (eGFR) | 41.6 ± 14.2 |
Adverse event monitoring in our patient population; did patients have treatment related adverse events and if so, how many events
| Participants | Clazakizumab (Anti-IL-6 Monoclonal) |
|---|---|
| Incidence of Treatment-related Adverse Events | 0 |
Collected over 1 year. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Clazakizumab (Anti-IL-6 Monoclonal) | 0/10 (0%) | 2/10 (20%) | 10/10 (100%) |
| Event | Clazakizumab (Anti-IL-6 Monoclonal) |
|---|---|
| Sepsis due to pyelonephritisRenal and urinary disorders | 2/10 |
| Event | Clazakizumab (Anti-IL-6 Monoclonal) |
|---|---|
| PyelonephritisRenal and urinary disorders | 3/10 |
| Respiratory Tract InfectionRespiratory, thoracic and mediastinal disorders | 3/10 |
| EdemaGeneral disorders | 3/10 |
| Herpes ZosterInfections and infestations | 2/10 |
| Cough and/or ColdInfections and infestations | 2/10 |
| Arm swelling/cellulitisSkin and subcutaneous tissue disorders | 2/10 |
| Excision of skin cancer lesionSkin and subcutaneous tissue disorders | 2/10 |
| AnemiaBlood and lymphatic system disorders | 2/10 |
| EBV ViremiaInfections and infestations | 1/10 |
| C difficile infectionInfections and infestations | 1/10 |
| Age, Continuous(years) | Clazakizumab (Anti-IL-6 Monoclonal) |
|---|---|
| Median | 51 (21 to 70) |
| Sex: Female, Male(Participants) | Clazakizumab (Anti-IL-6 Monoclonal) |
|---|---|
| Female | 3 |
| Male | 7 |
| Ethnicity (NIH/OMB)(Participants) | Clazakizumab (Anti-IL-6 Monoclonal) |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 10 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(Participants) | Clazakizumab (Anti-IL-6 Monoclonal) |
|---|---|
| United States | 10 |
| estimated Glomerular Filtration Rate (eGFR)(ml/min/1.73m2) | Clazakizumab (Anti-IL-6 Monoclonal) |
|---|---|
| Mean | 38.11 ± 12.23 |
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Studies of the drug tested here: Clazakizumab
Stanley Jordan, MD