A Prospective, Observational Long-term Follow-up Trial of Kidney Transplant Patients Treated With Imlifidase or Plasma Exchange After an Active/Chronic Active Antibody-Mediated Rejection Episode

Brief Summary

Detailed Description

AMR is one of the most challenging adverse events following kidney transplantation and a major cause of graft dysfunction and graft loss. AMR is triggered by donor-specific antibodies (DSA).Transplant glomerulopathy is a known consequence of persistent DSA positivity which results in graft failure and return to dialysis with attendant consequences for the patient and financial costs for the health care system. The time from transplantation to onset of clinical symptoms of AMR varies largely between individuals. An early AMR (\<30 days post-transplant) is commonly classified as active AMR and most often triggered by an immunological recall response with pre-existing DSA. A late AMR (\>30 days post-transplant) is classified as either active or chronic active AMR and is caused by either a recall DSA response or newly developing naïve immune response associated with de novo DSA production. There is no currently approved therapy for AMR and patients are often treated with a combination of therapies i.e., high dose IVIg +/- rituximab, PE with low dose IVIg +/- rituximab, and eculizumab which makes analysis of efficacy of any single agent difficult. Hence, there is a large unmet clinical need for new therapies to treat AMR. Imlifidase is an IgG-degrading enzyme of Streptococcus pyogenes that cleaves all four human subclasses of IgG with high efficacy and specificity. The rapidity of the IgG cleavage by imlifidase is considered a major advantage as compared with PE, which often requires several rounds over several days to achieve a sufficient DSA reduction. Within a few hours after imlifidase dosing, the entire pool of IgG is completely cleaved and thereby a window where IgG levels are kept very low for approximately one week is created. The short-term efficacy and safety of imlifidase in active and chronic active AMR is being investigated in a randomized, open-label, multi-centre trial, using PE as an active control (i.e. the feeder study: 16-HMedIdeS-12). A total of 30 subjects will be included in this study (20 in the imlifidase arm and 10 in the plasma exchange arm). The primary objective is to investigate the efficacy of imlifidase in removing DSA in patients who are experiencing an AMR episode after kidney transplantation. While a rapid removal of DSA by imlifidase might be expected, DSA is likely to rebound unless well-controlled by concomitant immunosuppressive therapy. Therefore, there is also a need to address the long-term outcome of imlifidase as an AMR therapy. This will be studied during an extended follow-up period of 3 years in this study. Data for parameters such as kidney graft survival, patient survival, kidney function, treatment of rebound of donor specific antibodies (DSA) and anti-drug antibodies (ADAs) will be collected.

Primary Outcomes

Secondary Outcomes

• ADA Levels(1,2 and 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12))
• Overall Graft Survival at Year 2(2 years after start of AMR treatment in feeder study (16-HMedIdeS-12))
• Overall Graft Survival at Year 1(1 year after start of AMR treatment in feeder study (16-HMedIdeS-12))
• Patient Survival at Year 3(3 years after start of AMR treatment in feeder study (16-HMedIdeS-12))
• Kidney Function as Evaluated by eGFR(1, 2 and 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12))
• Kidney Function as Evaluated by S/P-creatinine(1, 2 and 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12))
• Number of Participants With Presumed or Biopsy Proven AMR Episodes(3 years after start of AMR treatment in feeder study (16-HMedIdeS-12))
• Number of Participants With Presumed or Biopsy-proven Rejection Episodes (Other Than AMR Episodes)(3 years after start of AMR treatment in feeder study (16-HMedIdeS-12))
• DSA Levels(1, 2 and 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12))