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NCT03380377

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

Completed Phase 1, PHASE2 Results posted Last updated 6 May 2025
What this trial tests

Phase 1, PHASE2 trial testing Clazakizumab in Antibody-mediated Rejection in 10 participants. Completed in 16 April 2024.

Timeline
21 February 2018
Primary endpoint
16 April 2024
16 April 2024

Quick facts

Lead sponsorStanley Jordan, MD
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment10
Start date21 February 2018
Primary completion16 April 2024
Estimated completion16 April 2024
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Stanley Jordan, MD

Who can join

Adults 15 to 75, any sex, with Antibody-mediated Rejection or Kidney Transplant; Complications. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Donor Specific Antibody (DSA) Elimination or Reduction Based on Luminex HLA Testing Primary · 12 months

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.

GroupValue95% CI
Clazakizumab (Anti-IL-6 Monoclonal)7
Number of Participants With Stabilization of Clinical Features of cABMR Via BANFF Biopsy Grading Criteria. Primary · 6 months

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.

GroupValue95% CI
Clazakizumab (Anti-IL-6 Monoclonal)9
Stabilization in Estimated Glomerular Filtration Rate (eGFR) Secondary · 12 months

Serum creatinine (mg/dl) collected to calculate eGFR

GroupValue95% CI
Clazakizumab (Anti-IL-6 Monoclonal)41.6± 14.2
Incidence of Treatment-related Adverse Events Secondary · 12 months

Adverse event monitoring in our patient population; did patients have treatment related adverse events and if so, how many events

GroupValue95% CI
Clazakizumab (Anti-IL-6 Monoclonal)0

Adverse events — posted to ClinicalTrials.gov

Time frame: 1 year. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Clazakizumab (Anti-IL-6 Monoclonal)
Serious: 2/10 (20%)
Deaths: 0/10

Serious adverse events (1 terms)

ReactionSystemClazakizumab (Anti-IL-6 Mo…
Sepsis due to pyelonephritisRenal and urinary disorders
Other adverse events (20 terms — click to expand)

ReactionSystemClazakizumab (Anti-IL-6 Mo…
PyelonephritisRenal and urinary disorders
Respiratory Tract InfectionRespiratory, thoracic and mediastinal disorders
EdemaGeneral disorders
Herpes ZosterInfections and infestations
Cough and/or ColdInfections and infestations
Arm swelling/cellulitisSkin and subcutaneous tissue disorders
Excision of skin cancer lesionSkin and subcutaneous tissue disorders
AnemiaBlood and lymphatic system disorders
EBV ViremiaInfections and infestations
C difficile infectionInfections and infestations
InfluenzaInfections and infestations
Abdominal painGastrointestinal disorders
FeverGeneral disorders
Eczema/warts on handsSkin and subcutaneous tissue disorders
Intermittent dizzinessGeneral disorders
Itching on legsSkin and subcutaneous tissue disorders
Swollen hand after exerciseGeneral disorders
Uric acid elevated/gout in big toeMusculoskeletal and connective tissue disorders
AlopeciaSkin and subcutaneous tissue disorders
VaginitisReproductive system and breast disorders

Most-reported serious reactions: Sepsis due to pyelonephritis.

Data from ClinicalTrials.gov NCT03380377 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The therapeutic challenge of late antibody-mediated kidney allograft rejection.
    Böhmig GA, Eskandary F, Doberer K, Halloran PF. · · 2019 · cited 87× · PMID 30955215 · DOI 10.1111/tri.13436
  2. Tackling Chronic Kidney Transplant Rejection: Challenges and Promises.
    Lai X, Zheng X, Mathew JM, Gallon L, et al · · 2021 · cited 66× · PMID 34093552 · DOI 10.3389/fimmu.2021.661643
  3. IL-6 Directed Therapy in Transplantation.
    Miller CL, Madsen JC. · · 2021 · cited 50× · PMID 34099967 · DOI 10.1007/s40472-021-00331-4
  4. Emerging therapies in rheumatoid arthritis: focus on monoclonal antibodies.
    Senolt L. · · 2019 · cited 44× · PMID 31508202 · DOI 10.12688/f1000research.18688.1
  5. Evaluation of Clazakizumab (Anti-Interleukin-6) in Patients With Treatment-Resistant Chronic Active Antibody-Mediated Rejection of Kidney Allografts.
    Jordan SC, Ammerman N, Choi J, Huang E, et al · · 2022 · cited 37× · PMID 35497778 · DOI 10.1016/j.ekir.2022.01.1074
  6. Antibody-mediated rejection: prevention, monitoring and treatment dilemmas.
    Rodriguez-Ramirez S, Al Jurdi A, Konvalinka A, Riella LV. · · 2022 · cited 32× · PMID 35950887 · DOI 10.1097/mot.0000000000001011
  7. Clazakizumab for the treatment of chronic active antibody-mediated rejection (AMR) in kidney transplant recipients: Phase 3 IMAGINE study rationale and design.
    Nickerson PW, Böhmig GA, Chadban S, Kumar D, et al · · 2022 · cited 27× · PMID 36550562 · DOI 10.1186/s13063-022-06897-3
  8. IL-6 and diabetic kidney disease.
    Zhang L, Xu F, Hou L. · · 2024 · cited 16× · PMID 39749325 · DOI 10.3389/fimmu.2024.1465625

Verify or expand the search:

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing