clazakizumab (CSL300) / CSL Behring, Lundbeck - LARVOL DELTA

Clazakizumab: A Therapeutic Approach for Patients With Late Antibody-Mediated Rejection. (PubMed, Kidney Int Rep) - No abstract available

Journal • Antibody-mediated Rejection

The Effects of Clazakizumab on Peripheral Blood and Kidney Transcriptomes in Patients With Late Antibody-Mediated Rejection. (PubMed, Kidney Int Rep) - "We also found a kidney plasma cell gene-rich module that positively correlated with circulating DSAs; however, this was not significantly downregulated by CLZ. Overall, our results provide mechanistic insights into the effects and limitations, of IL-6 neutralization in humans in the context of AMR."

Journal • Antibody-mediated Rejection • Inflammation • IL6

Effect of Clazakizumab on Neutrophil-to-Lymphocyte Ratio in Patients Receiving Maintenance Hemodialysis: Secondary Analysis of the POSIBIL6ESKD Phase 2b Trial (KIDNEY WEEK 2025) - "The Phase 3 component of the trial will provide definitive evidence on the effects of clazakizumab on CV outcomes in this population. Figure: Repeated measures of NLR for the placebo and pooled clazakizumab groups"

Clinical • P2b data • Atherosclerosis • Cardiovascular • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • CRP • IL6

Population Pharmacokinetic and Pharmacokinetic-Pharmacodynamic Analysis for Clazakizumab in Patients With End-Stage Kidney Disease Undergoing Dialysis. (PubMed, Clin Transl Sci) - "In addition, the proportion of subjects with hs-CRP concentrations below 2 mg/L at Week 12 was predicted to be 67.7%, 76.7%, and 82.6%, respectively, for these 3 dose groups. These modeling and simulation results support the dose selection of clazakizumab 5 mg IV every 4 weeks in the phase 3 placebo-controlled trial to evaluate the impact of IL-6 inhibition via clazakizumab administration upon cardiovascular events."

Clinical • Journal • PK/PD data • Cardiovascular • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • CRP

Improving Physical Function in Older Adults Using an Anti-inflammation Drug: The RIGHT Study (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: Anne B. Newman | Recruiting ➔ Active, not recruiting

Enrollment closed • Inflammation • IL6

The Impact of Tocilizumab and Clazakizumab on Molecular Rejection and Injury Scores in Chronic-Active Antibody-Mediated Rejection in Kidney Transplantation: A Case Series (WTC 2025) - "Compared to optimized IS alone, TCZ and CKZ did not reduce molecular rejection and AMR classifier scores or prevent the progression from early-stage to fully-developed AMR. However, TCZ showed a potential reduction in IRRAT scores, which have been associated with kidney allograft failure, suggesting possible benefits. Further studies are needed and should consider biopsy-based transcript diagnostics in the assessment of treatment responses."

Clinical • Antibody-mediated Rejection • Transplantation • IL6R

PrecISE (Precision Interventions for Severe and/or Exacerbation-Prone Asthma) Network Study (clinicaltrials.gov) - P2 | N=395 | Completed | Sponsor: University of North Carolina, Chapel Hill | Active, not recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Mar 2025

Trial completion • Trial completion date • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Targeting IL-6 in antibody-mediated kidney transplant rejection. (PubMed, Clin Kidney J) - "Additionally, the anti-IL-6 receptor antibody tocilizumab and the anti-IL-6 antibody clazakizumab have been studied for the treatment of naïve as well as resistant antibody-mediated kidney allograft rejection with mixed results in observational studies and early clinical development...Investigator-initiated clinical development continues in a smaller phase 3 trial testing tocilizumab (INTERCEPT). In this viewpoint article, we evaluate the pathophysiology of IL-6 in antibody-mediated kidney allograft rejection along with the current status of the clinical development of IL-6 targeting therapies for antibody-mediated kidney allograft rejection episodes within the wider frame of IL-6 targeting therapies in kidney failure that are considered the major causes of graft loss in kidney transplantation."

Journal • Review • Antibody-mediated Rejection • Hematological Disorders • Immunology • Inflammation • Transplant Rejection • Transplantation • IL6

A Phase II Precision Medicine Trial of Clazakizumab for the Treatment of Severe Asthma (ATS 2025) - No abstract available

Late-breaking abstract • P2 data • Asthma • Immunology • Respiratory Diseases

B6 PRECISION MEDICINE IN SEVERE ASTHMA: LATE-BREAKING RESULTS FROM THE PRECISE TRIAL (ATS 2025) - "Objectives describe new thinking about how to design and interpret biomarker-stratified adaptive platform trialsdescribe new findings about the following interventions targeting new pathways in severe and exacerbation-prone asthma: medium chain triglycerides, cavosonstat, imatinib, Broncho-Vaxom®, and clazakizumablearn how established and new biomarkers can predict asthma severity and response to therapy. The learner can apply this new knowledge in clinical practice to improve the care of severe asthmatics"

Late-breaking abstract • Asthma • Immunology • Respiratory Diseases

Clazakizumab treatment effects on kidney transcriptomes in chronic ABMR (BTS-NHSBT JAC 2025) - No abstract available

Combined Dose-Finding and CV Outcomes Study With CSL300 (Clazakizumab) in Adult Subjects With ESKD Undergoing Dialysis (clinicaltrials.gov) - P2/3 | N=2310 | Recruiting | Sponsor: CSL Behring | Trial completion date: Dec 2028 ➔ Aug 2029 | Trial primary completion date: Dec 2028 ➔ Aug 2029

Trial completion date • Trial primary completion date • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease • CRP

Effects of Clazakizumab on Anemia and Iron Metabolism in Patients with Kidney Failure. (PubMed, J Am Soc Nephrol) - No abstract available

Journal • Anemia • Hematological Disorders • Renal Disease

CTLA-4IG + ANTI-IL-6/IL-6R RESULTS IN LONG-TERM REJECTION-FREE GRAFT SURVIVAL IN HIGHLY-HLA SENSITIZED PATIENTS. . (WRMC 2025) - "Two patients 100% cPRA & +FCMX at tx were desensitized with clazakizumab (anti-IL-6, claza)...Two patients received tocilizumab (anti-IL-6R,) were transitioned to CNI-free regimens at 2 & 11 years post-tx... The combination of CTLA4-Ig + anti-IL-6/IL-6R appears to offer benefits in DSA reduction, prevention of dnDSA and AMR/CMR after >4.5 yrs in HS patients. Importantly, CNI toxicity abated in all patients. Although limited, the reductions in CD8+TEFF/MEM, BMEM, NK, and TFH cells with increasing TREG & BREG cell populations suggest immune modulation vs."

Clinical • Immune Modulation • Immunology • CD8 • IL6R

Network meta-analysis of pharmacological treatment for antibody-mediated rejection after organ transplantation. (PubMed, Front Immunol) - "The results indicated that the increase in eGFR by eculizumab (SUCRA score: 81) appeared to be more promising. The decrease in MFI by bortezomib (SUCRA score: 72.3), rituximab (SUCRA score: 68.2), and clazakizumab (SUCRA score: 67.1) demonstrated better efficacy...Clazakizumab appears to be more effective in reducing infections. https://www.crd.york.ac.uk/prospero/, identifier CRD42024546483."

Clinical • Journal • Retrospective data • Review • Antibody-mediated Rejection • Infectious Disease • Transplantation

Effects of Interleukin-6 Inhibition with Clazakizumab on Anemia and Iron Parameters in Patients with Kidney Failure (KIDNEY WEEK 2024) - "Through anti-IL6 effects, clazakizumab may improve iron utilization and contribute to anemia correction in patients receiving dialysis. Larger and longer-term data from the ongoing Phase 3 study will provide additional insights."

Clinical • Anemia • Cardiovascular • Diabetes • Diabetic Nephropathy • Hematological Disorders • Inflammation • Metabolic Disorders • Renal Disease • CRP • IL6

Clazakizumab in Chronic Active Antibody-Mediated Kidney Transplant Rejection: Results of the IMAGINE Phase 3 Study (KIDNEY WEEK 2024) - P3 | "Despite encouraging phase 2 results, the data from the IMAGINE IA did not support continuation. Nonetheless, this was the largest placebo-controlled study in KTRs with caAMR and was first transplant study for which the FDA accepted a 1-yr eGFR slope as a RLSE. No safety concerns were noted."

P3 data • Antibody-mediated Rejection • Gastrointestinal Disorder • Immunology • Inflammation • Transplant Rejection • Transplantation • IL6

IL-6 Inhibition with Clazakizumab in Patients Receiving Maintenance Dialysis (KIDNEY WEEK 2024) - No abstract available

Clinical • Nephrology

A to X Nephrology Hot Topics: Autoantibodies, Clazakizumab, Semaglutide (FLOW), and Xenotransplantation (KIDNEY WEEK 2024) - "Learning Pathway(s). Diabetic Kidney Disease Kidney Transplantation ."

Chronic Kidney Disease • Diabetic Nephropathy • Glomerulonephritis • Nephrology • Renal Disease • Transplantation

Combined Dose-Finding and CV Outcomes Study With CSL300 (Clazakizumab) in Adult Subjects With ESKD Undergoing Dialysis (clinicaltrials.gov) - P2/3 | N=2310 | Recruiting | Sponsor: CSL Behring | Enrolling by invitation ➔ Recruiting

Enrollment status • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Dyslipidemia • Nephrology • Renal Disease • CRP

New therapies for highly sensitized patients on the waiting list. (PubMed, Kidney360) - "Administering these agents alone or in combination will advance our ability to effectively desensitize patients and maintain durable suppression post-transplant. After many years of limited options, advanced therapeutics will likely improve efficacy of desensitization and improve access to kidney transplantation for highly-HLA sensitized patients."

Journal • Antibody-mediated Rejection • Transplantation

PrecISE (Precision Interventions for Severe and/or Exacerbation-Prone Asthma) Network Study (clinicaltrials.gov) - P2 | N=395 | Active, not recruiting | Sponsor: University of North Carolina, Chapel Hill | Recruiting ➔ Active, not recruiting | N=600 ➔ 395

Enrollment change • Enrollment closed • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Granulomatous Tubulointerstitial Nephritis in a Kidney Allograft: Treatment with Interleukin-6 Receptor Antagonist Stabilises Kidney Function. (PubMed, J Clin Med) - "We revised his underlying diagnosis from cryopyrin-associated periodic syndrome to early-onset sarcoidosis with wild-type NOD2 and established a rationale to use the interleukin-6 (IL-6) receptor blocker tocilizumab (TCZ). We identified 18 reports with 417 unique patients treated with TCZ for indications including HLA-desensitisation, transplant immunosuppression induction, treatment of chronic antibody-mediated rejection, and treatment of subclinical rejection. Both TCZ and the direct IL-6 inhibitor clazakizumab are being studied in ongoing randomised control trials."

Journal • Review • Antibody-mediated Rejection • Immunology • Inflammation • Nephrology • Sarcoidosis • Transplantation

Combined Dose-Finding and CV Outcomes Study With CSL300 (Clazakizumab) in Adult Subjects With ESKD Undergoing Dialysis (clinicaltrials.gov) - P2/3 | N=2310 | Enrolling by invitation | Sponsor: CSL Behring | Active, not recruiting ➔ Enrolling by invitation

Enrollment open • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Dyslipidemia • Nephrology • Renal Disease • CRP

A Phase 2b/3 trial assessing IL-6 inhibition with Clazakizumab in patients with cardiovascular disease or diabetes on dialysis: Results from Phase 2b (ERA-EDTA 2024) - P2/3 | "In patients undergoing dialysis with documented inflammation, clazakizumab resulted in a robust reduction in inflammatory biomarkers that are associated with cardiovascular events and increased albumin. The safety profile of clazakizumab appeared acceptable and consistent with the drug's mechanism of action. These data support continuing to the Phase 3 part of the trial to determine the safety and efficacy of clazakizumab in reducing major cardiovascular events."

Clinical • Late-breaking abstract • P2/3 data • P2b data • Cardiovascular • Diabetes • Hematological Disorders • Infectious Disease • Inflammation • Metabolic Disorders • Neutropenia • Thrombocytopenia • CRP • IL6