CSL300 for Kidney Failure

(POSIBIL6ESKD Trial)

Recruiting at 398 trial locations

Overseen By Trial Registration Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: CSL Behring

Must not be taking: Immunosuppressants

Disqualifiers: Abnormal LFTs, Life-threatening disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

2310 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CSL300 (also known as Clazakizumab, ALD-518, or BMS-945429) to determine its effectiveness for people with end-stage kidney disease on dialysis who have systemic inflammation. The first part of the trial identifies the right dose, while the second part evaluates CSL300's impact on heart health and safety. Participants must have end-stage kidney disease with either diabetes or heart disease and must have been on dialysis for at least 12 weeks. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using systemic immunosuppressant drugs.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that CSL300, also known as Clazakizumab, is under study for its safety and effectiveness in patients with end-stage kidney disease on dialysis. Earlier studies examined patient tolerance to CSL300 and found that most people tolerate it well.

Some patients reported side effects, usually mild to moderate, such as reactions at the injection site or mild flu-like symptoms. Importantly, serious side effects were uncommon in these studies.

CSL300 is also being tested for its potential to reduce heart-related problems in these patients. It targets a specific process in the body that can cause inflammation, a common issue for people with kidney disease.

Since CSL300 is now in advanced testing stages, earlier studies deemed it safe enough for continued research. If considering joining a trial, these findings might reassure you about CSL300's safety. However, discussing any concerns with the trial team or your doctor is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney failure?

Researchers are excited about CSL300 for kidney failure because it offers a potentially unique approach to treatment. Unlike existing therapies like dialysis or kidney transplantation, CSL300 is being tested in various doses and phases to optimize its effectiveness. This treatment is delivered intravenously, which can be more direct and efficient. It may target underlying disease mechanisms in a way that current treatments do not, potentially improving kidney function more effectively. The hope is that CSL300 can provide a new option that could reduce the need for invasive procedures and improve quality of life for patients with kidney failure.

What evidence suggests that this trial's treatments could be effective for kidney failure?

Studies have shown that CSL300, also known as clazakizumab, can help patients with end-stage kidney disease (ESKD) on dialysis by reducing inflammation. Earlier research demonstrated that CSL300 lowered levels of certain blood substances indicating inflammation. By targeting these substances, CSL300 may reduce the risk of heart problems in these patients. Early findings suggest it could significantly improve heart health for people with kidney failure. Participants in this trial will receive different doses of CSL300 or a placebo to further evaluate its effectiveness. ^{1 2 4 5 6}

Who Is on the Research Team?

Study Director

Principal Investigator

CSL Behring LLC

Are You a Good Fit for This Trial?

Adults with end-stage kidney disease (ESKD) on dialysis for at least 12 weeks can join this trial. They must also have diabetes or atherosclerotic cardiovascular disease (ASCVD), and signs of inflammation shown by high hs-CRP levels. People who were in the earlier part of the study, have certain gastrointestinal conditions, use strong immune system drugs, or have abnormal liver tests cannot participate.

Inclusion Criteria

I have been on dialysis for my kidney failure for at least 12 weeks.

I have been diagnosed with diabetes or heart and blood vessel disease.

Your blood test shows high levels of hs-CRP (a marker of inflammation).

Exclusion Criteria

Subjects who participated in Part 1 (phase 2b) are not eligible to participate in Part 2 (phase 3)

I have had GI perforation, inflammatory bowel disease, or peptic ulcer disease.

I am currently taking drugs that suppress my immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Finding (Phase 2b)

Participants receive varying doses of CSL300 or placebo to determine optimal dosing

12 weeks

Cardiovascular Outcomes Assessment (Phase 3)

Assessment of the efficacy of CSL300 on cardiovascular outcomes and safety in subjects with systemic inflammation and ESKD

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CSL300
• Placebo

Trial Overview The study is testing CSL300 against a placebo to find the right dose and see if it helps with heart-related outcomes in patients with ESKD undergoing dialysis. It's organized into two parts: first finding the correct dosage and then checking its effectiveness and safety.

How Is the Trial Designed?

Group I: CSL300 (medium dose)(Phase 2b) Experimental Treatment 1 Intervention

IV administration

Group II: CSL300 (low dose)(Phase 2b) Experimental Treatment 1 Intervention

Intravenous (IV) administration

Group III: CSL300 (high dose)(Phase 2b) Experimental Treatment 1 Intervention

IV administration

Group IV: CSL300 (Phase 3) Experimental Treatment 1 Intervention

IV administration

Group V: Placebo (Phase 2b) Placebo Group 1 Intervention

IV administration

Group VI: Placebo (Phase 3) Placebo Group 1 Intervention

IV administration

Who Is Running the Clinical Trial?

CSL Behring

Lead Sponsor

Trials

204

Recruited

1,207,000+

Dr. Paul McKenzie

CSL Behring

Chief Executive Officer since 2023

PhD in Chemical Engineering from Carnegie Mellon University, B.S. in Chemical Engineering from the University of Pennsylvania

Dr. Bill Mezzanotte

CSL Behring

Chief Medical Officer since 2021

MD from Duke University

Published Research Related to This Trial

Clazakizumab, an anti-IL-6 treatment, was well tolerated in a pilot study of 20 highly HLA-sensitized patients, leading to significant reductions in HLA alloantibodies and enabling 18 out of 20 patients to successfully receive transplants without a rebound of donor-specific antibodies.

The treatment was associated with an increase in regulatory immune cells post-transplant, although antibody-mediated rejection occurred in three patients, indicating that while clazakizumab shows promise for desensitization, further randomized controlled trials are needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clazakizumab for desensitization in highly sensitized patients awaiting transplantation. Vo, AA., Huang, E., Ammerman, N., et al.[2023]

The combination of rituximab and belimumab was found to be safe for patients with refractory lupus nephritis, showing no increase in adverse events compared to those receiving rituximab alone.

While the addition of belimumab did not improve clinical efficacy compared to rituximab and cyclophosphamide alone, it did lead to a greater reduction in certain B cell populations, suggesting a mechanism that enhances the negative selection of autoreactive B cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Randomized Trial of Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis. Atisha-Fregoso, Y., Malkiel, S., Harris, KM., et al.[2022]

In a study of 1355 patients with lupus nephritis treated with tacrolimus for 5 years, the treatment was found to be well tolerated, with serious adverse drug reactions occurring mainly in the first 28 weeks and no significant increase in risk over time.

Tacrolimus significantly improved key health markers related to lupus nephritis, such as urine protein levels and anti-dsDNA antibody levels, while maintaining a low cumulative rate of progression to renal failure (6.6% at Year 5) and manageable relapse rates (30.6% at Year 5).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Safety and Effectiveness of Tacrolimus in Patients With Lupus Nephritis: 5-year Interim Postmarketing Surveillance Study in Japan (TRUST). Takeuchi, T., Wakasugi, N., Uno, S., et al.[2021]

In a study of 25 patients with active lupus nephritis, sirukumab did not show the expected efficacy in reducing proteinuria compared to placebo, with a median percent change of 0.0% in the sirukumab group versus a -43.3% increase in the placebo group at week 24.

The safety profile of sirukumab raised concerns, as 47.6% of patients experienced serious adverse events, primarily infections, indicating that while the treatment was not effective, it also posed significant safety risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Treatment With Sirukumab (CNTO 136) in Patients With Active Lupus Nephritis. Rovin, BH., van Vollenhoven, RF., Aranow, C., et al.[2019]

The Phase 3 IMAGINE study is the first large-scale trial evaluating clazakizumab, a monoclonal antibody targeting interleukin-6, for treating chronic active antibody-mediated rejection (AMR) in approximately 350 kidney transplant recipients.

Clazakizumab aims to reduce donor-specific antibody production and stabilize kidney function, with the trial using the eGFR slope as a key measure to predict graft loss, potentially leading to faster approval of new treatments for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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., et al.[2022]

A single dose of alemtuzumab (30 mg) was used in a prospective study to create a steroid and calcineurin inhibitor-free regimen for kidney transplants, showing promising results over a follow-up period of up to 48 months.

The study indicated that patients receiving sirolimus had a higher glomerular filtration rate and fewer acute rejection episodes compared to those on tacrolimus, suggesting that this regimen may improve kidney function and reduce the need for traditional immunosuppressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alemtuzumab preconditioning allows steroid-calcineurin inhibitor-free regimen in live-donor kidney transplant. Refaie, AF., Mahmoud, KM., Ismail, AM., et al.[2017]

In a study of 21 pediatric patients who received deceased donor kidney transplants, the use of a single dose of alemtuzumab for induction and a steroid-free immunosuppression protocol resulted in a 95% graft survival rate and 100% patient survival over an average follow-up of 32 months.

The approach was found to be safe, with no cases of serious infections like cytomegalovirus or polyoma BK viral nephropathy, although three patients experienced acute rejection due to non-adherence to the treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alemtuzumab with corticosteroid minimization for pediatric deceased donor renal transplantation: a seven-yr experience. Supe-Markovina, K., Melquist, JJ., Connolly, D., et al.[2019]

Eculizumab shows promising efficacy in improving renal function in patients with systemic lupus erythematosus (SLE) who have renal involvement, particularly in cases of thrombotic microangiopathy (TMA) and refractory lupus nephritis, based on a review of six publications.

All patients treated with eculizumab demonstrated sustained improvement in renal function and normalization of complement levels over a median follow-up of 9 months, indicating its potential as a therapeutic option for severe cases of SLE with renal complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanding the therapeutic options for renal involvement in lupus: eculizumab, available evidence. Sciascia, S., Radin, M., Yazdany, J., et al.[2020]

Alemtuzumab, a humanized monoclonal antibody, is being increasingly used in renal transplantation to provide intense immunosuppression while minimizing or avoiding the nephrotoxic effects of calcineurin inhibitors (CNIs) and the adverse effects of steroids.

The use of alemtuzumab allows for rapid and profound depletion of lymphocytes, which may improve long-term graft outcomes by reducing the need for traditional immunosuppressive agents that can harm kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of alemtuzumab (Campath-1H) in renal transplantation. Pham, PT., Lipshutz, GS., Pham, PT., et al.[2021]

Rituximab has been found to be safe and effective for treating non-renal systemic lupus erythematosus (SLE), particularly in improving disease activity and reducing the need for steroids, based on a review of 26 studies involving 1,231 patients.

While rituximab showed positive effects on conditions like arthritis and thrombocytopenia, relapses of disease were noted, and further high-quality studies are necessary to evaluate the long-term effects of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rituximab in the treatment of non-renal systemic lupus erythematosus: a systematic review. Cobo-Ibáñez, T., Loza-Santamaría, E., Pego-Reigosa, JM., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05485961

Study Details | NCT05485961 | Combined Dose-Finding ... ... Outcome Study to Investigate the Efficacy and Safety of CSL300 (Clazakizumab) in Subjects With End Stage Kidney Disease Undergoing Dialysis. Conditions.

2. domsccr.stanford.edu domsccr.stanford.edu/wp-content/uploads/2025/04/SCCR-CSL300-Poster-Sept-2024-Read-Only.pdf

POSIBIL6 Study: Cardiovascular Outcome Study for Patients ... It was hypothesized that CSL300 could reduce the occurrence of cardiovascular events in patients receiving maintenance dialysis by modulating excess IL-6-.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11333272/

IL-6 inhibition with clazakizumab in patients receiving ... The results of this trial indicate that in patients receiving maintenance dialysis, clazakizumab reduced inflammatory biomarkers associated with ...

4. trialstoday.org trialstoday.org/trial/NCT05485961

Combined Dose-Finding and CV Outcomes Study ... Combined Dose-Finding and CV Outcomes Study With CSL300 (Clazakizumab) in Adult Subjects With ESKD Undergoing Dialysis · Purpose · Conditions.

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05485961/combined-dose-finding-and-cv-outcomes-study-with-csl300-clazakizumab-in-adult-subjects-with-eskd-undergoing-dialysis

Combined Dose-Finding and CV Outcomes Study With ... Combined Dose-Finding and CV Outcomes Study With CSL300 (Clazakizumab) in Adult Subjects With ESKD Undergoing Dialysis. Last updated: August ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9772593/

Clazakizumab for the treatment of chronic active antibody ... We report the design of the Phase 3 IMAGINE study (NCT03744910) to evaluate the safety and efficacy of clazakizumab for the treatment of chronic active AMR.