An Long-term Follow-up Trial of Kidney Tx Patients Treated With Imlifidase or PE After an AMR

NCT ID: NCT04711850

Last Updated: 2025-05-28

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 18 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-01-20
• Study Completion Date: 2023-03-30

Brief Summary

The aim of this trial is to collect data and provide a better understanding of the long-term outcome of imlifidase treatment on active or chronic active antibody-mediated rejection (AMR) in kidney transplant recipients. This is done by collecting data during an extended follow-up period of 3 years of clinical study trial 16-HMedIdeS-12, in which patients received either imlifidase or plasma exchange (PE) as AMR treatment. 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) are collected.

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.

Conditions

Kidney Transplant Rejection

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Imlifidase treatment in feeder Study 16-HMedIdeS-12

No treatment is given in this long-term follow-up study. In the feeder study (16-HMedIdeS-12) the patients in this group were treated with imlifidase.

Imlifidase

Intervention Type: DRUG

Immunoglobulin G degrading enzyme of Streptococcus pyogenes

Plasma exchange (PE) treatment in feeder Study 16-HMedIdeS-12

No treatment is given in this long-term follow-up study. In the feeder study (16-HMedIdeS-12) the patients in this group were treated with PE.

No interventions assigned to this group

Interventions

Imlifidase

Immunoglobulin G degrading enzyme of Streptococcus pyogenes

Intervention Type: DRUG

Other Intervention Names

IdeS, HMED-IdeS

Eligibility Criteria

Inclusion Criteria

• Signed Informed Consent obtained before any trial-related procedures
• Willingness and ability to comply with the protocol
• Previous treatment with imlifidase or plasma exchange in the trial 16-HMedIdeS-12

Note: The primary objective of this trial is overall graft survival after treatment with imlifidase or plasma exchange. Therefore, subjects can also be included even if the subject did not fully complete the feeder trial follow up but was dosed with imlifidase or plasma exchange in the trial 16-HMedIdeS-12.

Exclusion Criteria

• Inability by the judgement of the investigator to participate in the trial for any other reason

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hansa Biopharma AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Operations

Role: STUDY_DIRECTOR

Hansa Biopharma AB

Locations

Universitätsklinik für Innere Medizin III, Klinische Abteilung für Nephrologie MUW

Vienna, , Austria

Hôpital Pellegrin

Bordeaux, , France

CHU Grenoble Alpes - Néphrologie, dialyse et transplantation

Grenoble, , France

Hôpital Saint-Louis. Service de Néphrologie et Transplantation

Paris, , France

Hôpital Necker - Service de Néphrologie - Transplantation

Paris, , France

Charité-Universitätsmedizin. Dept. of Nephrology and Medical Intensive Care

Berlin, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Countries

Austria; France; Germany

References

Halleck F, Bohmig GA, Couzi L, Rostaing L, Einecke G, Lefaucheur C, Legendre C, Montgomery R, Hughes P, Chandraker A, Wyburn K, Halloran P, Maldonado AQ, Sjoholm K, Runstrom A, Lefevre P, Tollemar J, Jordan S. A Randomized Trial Comparing Imlifidase to Plasmapheresis in Kidney Transplant Recipients With Antibody-Mediated Rejection. Clin Transplant. 2024 Jul;38(7):e15383. doi: 10.1111/ctr.15383.

Reference Type: DERIVED

PMID: 39023092 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-004777-49

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20-HMedIdes-18

Identifier Type: -

Identifier Source: org_study_id