Eli Khankin Shares Update on the P-III IMAGINE Study Protocol Published in American Journal of Transplantation

Shots:

Eli spoke about the P-III IMAGINE study protocol evaluating Clazakizumab along with 6 articles by several experts published in the American Journal of Transplantation
Eli then talked about Clazakizumab's potential mechanism of action currently under investigation
The interview shows how CSL Behring works to develop and deliver innovative therapies for people living with conditions in the immunology, hematology, cardiovascular and metabolic, respiratory, and transplant therapeutic areas

Smriti: Please provide details (ROA, MOA, formulations, etc) of the Clazakizumab for chronic active ABMR in kidney transplant recipients.

Eli Khankin: Clazakizumab is an investigational genetically engineered monoclonal antibody being studied in a Phase 3 clinical trial, IMAGINE, to potentially treat chronic active antibody-mediated rejection (ABMR) following kidney transplantation.

Chronic active ABMR occurs when the kidney transplant recipient has repetitive tissue injury resulting from antibodies directed at the transplanted organ, which usually results in areas of scarring and permanent damage that may also be accompanied by inflammation.

IL-6 is an emerging target for immune-mediated injury following a kidney transplant. This mechanism may disrupt several steps critical to T-cell and B-cell immune responses, decreasing donor-specific antibody production and inflammation and slowing the estimated glomerular filtration rate (eGFR) decline.

Smriti: Shed some light on the study design of the P-III IMAGINE clinical study.

Eli Khankin: IMAGINE is a Phase 3 placebo-controlled study evaluating the safety and efficacy of clazakizumab in 350 kidney transplant recipients with chronic active ABMR. It is the first large study to evaluate the safety and efficacy of direct IL-6 inhibition for the treatment of chronic active ABMR in kidney transplant recipients. More information on the study design as well as information on how to enroll patients in this study can be found on our partner page with the American Society of Transplantation, available here.

Smriti: Any additional information about the study protocol you can share?

Eli Khankin: The event-driven trial design of IMAGINE will follow patients until 221 occurrences of all-cause composite allograft loss events are observed. This is the first study to use eGFR slope at 12 months, which has demonstrated a strong correlation with the risk of graft failure in ABMR as a surrogate endpoint for graft loss.

Smriti: What strategies does CSL have to register Clazakizumab for approval as the drug approaches the end of its P-III?

Eli Khankin: We are driven by our promise to deliver life-saving medicines for patients worldwide.

Upon trial completion, we intend to present the results at a scientific meeting(s) and/or publish the findings in a peer-reviewed journal(s). We will work with regulatory authorities worldwide to complete submissions based on the IMAGINE study's final results.

Smriti: As mentioned, chronic active ABMR has no approved product for treatment, how does the company plan to educate HCPs.

Eli Khankin: CSL has identified transplantation as a priority area of focus based on the significant unmet needs faced by kidney transplant recipients. As chronic active ABMR is one of the lesser-known types of transplant rejection, we are initially focused on educating and raising awareness of chronic active ABMR among the healthcare professionals directly treating kidney transplant recipients. The recently launched partner page with AST Partner Connect provides educational information for transplant professionals through an infographic series highlighting chronic active ABMR.

Moving forward, we intend to launch additional educational initiatives aimed at nephrologists as well as the broader range of members of the multidisciplinary nephrology community to raise awareness and understanding of what chronic active ABMR is, how it differs from other types of rejection, and how to identify a patient experiencing it. As a final step in our educational efforts, we will expand our focus to transplant recipients, and their loved ones.

Smriti: In what geographies does CSL intend to market the product?

Eli Khankin: We are currently focused on recruitment for the IMAGINE trial and, pending the final results, will discuss these data with regulatory authorities around the globe.

Smriti: Can you please give a glimpse of CSL's pipeline apart from Clazakizumab?

Eli Khankin: In addition to clazakizumab, the other late-stage asset under investigation in the transplant therapeutic area is Alpha-1 Antitrypsin (CSL964). CSL964 is in Phase 3 trials for both the treatment and prevention of acute graft-versus-host-disease in high-risk patients receiving an allogeneic hematopoietic stem cell transplant (HSCT), a commonly used therapy for blood cancers.

Additionally, our strong R&D pipeline utilizes CSL’s rich and diverse expertise in plasma protein technology, recombinant technology, cell and gene therapy, as well as vaccines technology to develop and deliver innovative medicines that address unmet medical needs or enhance current treatments in therapeutic areas such as immunology, hematology, respiratory, cardiovascular and metabolic diseases, and vaccines. Our R&D portfolio focuses on innovation in new products, developing improved products, and manufacturing expertise ensuring our continued growth. Our ability to innovate and deliver life-saving medicines for patients worldwide has earned us a reputation for always putting patients first.

Smriti: How can eligible folks sign up for the IMAGINE trial?

Eli Khankin: The IMAGINE trial actively enrolls participants, with recruitment ongoing across North America, Europe, and Australia study sites. To learn more about this study and determine a patient's enrollment status, don't hesitate to contact the study research staff at clinicaltrials@cslbehring.com.

Image source: Canva

About Author:

Dr. Eliyahu Khankin

Dr. Eliyahu Khankin is an Executive Director of Clinical and Translational Development for the Transplant Therapeutic Area at CSL Behring. Trained as a Transplant Nephrologist, Dr. Khankin provides medical and disease area expertise, playing an integral role in shaping strategy as well as supporting programs in Solid Organ Transplant, particularly the Phase 3 study of Clazakizumab for the Treatment of Chronic Active Antibody-Mediated Rejection in Kidney Transplant Recipients (IMAGINE). Dr. Khankin's commitment to the medical advancement of nephrology and organ transplantation has earned him the recognition of being a Fellow of the American Society of Nephrology (FASN) and a Fellow of the American Society of Transplantation (FAST).