NCT Number: NCT05937750
A prospective, post-authorisation long-term follow-up trial of patients previously treated with imlifidase prior to kidney transplantation, including a non-comparative concurrent reference cohort.
This study is active but is not currently recruiting participants.
Notify Me19 year–76 year
All sexes
Interventional
Phase 3
Medizinische Universitaet Wien, Vienna, Austria
This is a long-term follow-up trial to the post-authorisation efficacy and safety (PAES) trial (trial 20-HMedIdeS-19). The trial will include patients who participated in the PAES trial and were transplanted with a new kidney after treatment with imlifidase (trial drug) or standard of care medication. Imlifidase is a medicine used to prevent the body from rejecting a newly transplanted kidney and is used before transplantation in adults who have antibodies against the donor kidney and are considered 'highly sensitised' based on a positive crossmatch test.
The purpose of this follow-up trial is to fulfil requirements from the European Medicines Agency (EMA) to continue to evaluate efficacy (kidney function) and safety (side effects) over time, for the patients who were transplanted with a new kidney in the PAES trial. The patients will be followed for up to 5 years after transplantation in the PAES trial to collect valuable long-term data.
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
Imlifidase is an immunoglobulin G (IgG)-degrading enzyme of Streptococcus pyogenes that is highly selective towards IgG. The cleavage of IgG generates one F(ab')2- and one homodimeric Fc-fragment and efficiently neutralizes Fc-mediated activities of IgG.
Other names: IdeS, HMED-IdeS, Idefirix
Normal transplantation routine Transplantation and pre- and post-transplantation therapies in accordance with the clinic's normal transplantation routine.
Time frame: 5-years after transplantation
Graft failure is defined as permanent return to dialysis for at least 6 weeks, re-transplantation, or nephrectomy. Patients not undergoing transplantation will be censored at time zero (i.e. at entry into the PAES trial). Transplanted patients not having an event (graft failure or death) will be censored at the last known date being alive and having a functioning graft.
The 5-year graft failure-free survival rates will be estimated using the Kaplan-Meier estimator. Time from enrolment to the first of death or graft failure will be used as time variable.
Time frame: 5-years after transplantation
Graft failure is defined as permanent return to dialysis for at least 6 weeks, re-transplantation, or nephrectomy. Patients not undergoing transplantation will be censored at time zero (i.e. at entry into the PAES trial). Transplanted patients not having an event (graft failure or death) will be censored at the last known date being alive and having a functioning graft.
The 5-year graft failure-free survival rates will be estimated using the Kaplan-Meier estimator. Time from enrolment to the first of death or graft failure will be used as time variable.
Time frame: 2 and 3-years after transplantation
Graft failure is defined as permanent return to dialysis for at least 6 weeks, re-transplantation, or nephrectomy. Patients not undergoing transplantation will be censored at time zero (i.e. at entry into the PAES trial). Transplanted patients not having an event (graft failure or death) will be censored at the last known date being alive and having a functioning graft.
The 2 and 3-year graft failure-free survival rates will be estimated using the Kaplan-Meier estimator. Time from enrolment to the first of death or graft failure will be used as time variable.
Time frame: 2, 3, and 5-years after transplantation
Kidney function assessed by eGFR and serum/plasma creatinine will be summarised over 5 years for the imlifidase group and the reference cohort.
eGFR is a measure of kidney function. The serum/plasma creatinine levels will be analysed and eGFR will be calculated according to the modification of diet in renal disease (MDRD) equation.
Reduced kidney function is characterised by a decreased eGFR value. For patients in the imlifidase group who are not successfully transplanted, or for any enrolled patients without a functioning graft, their eGFR values will be set to 0 mL/min.
Time frame: 2, 3, and 5-years after transplantation
Patient survival up to 2, 3 and 5 years, respectively, will be assessed for the imlifidase group and the reference cohort.
The 2, 3, and 5-year patient survival rates will be extracted from Kaplan-Meier curves.
Time frame: 2, 3, and 5-years after transplantation
Graft survival up to 2, 3 and 5 years, respectively, will be assessed for the imlifidase group and the reference cohort.
Graft survival will be presented with Kaplan-Meier curves. Graft failure is defined as permanent return to dialysis for at least 6 weeks, re-transplantation, or nephrectomy. Patients who die will be censored at time of death.
Time frame: 2, 3, and 5-years after transplantation
HLA antibodies will be analysed using an IgG single antigen solid-phase immunoassay for class I and class II (SAB-HLA).
Donor specific antibodies (DSAs) are identified by using the human leukocyte antigen (HLA) profile data from the donor and the recipient to identify HLA-mismatches.
The mean fluorescence intensity (MFI) will be summarized for all DSAs with an MFI of ≥1000 at any time during the trial (or the PAES trial).
Time frame: 2, 3, and 5-years after transplantation
Determination of anti-imlifidase IgG (ADA) concentration in serum will be performed centrally using a customised ImmunoCAP to evaluate imlifidase long-term immunogenicity.
Time frame: 2, 3, and 5-years after transplantation
For-cause biopsies will be obtained to confirm diagnosis for suspected AMRs in both treatment arms.
The biopsies will be analysed locally and centrally and evaluated according to Banff criteria version 2017 or later.
Time frame: 2, 3, and 5-years after transplantation
For-cause biopsies will be obtained to confirm diagnosis for suspected CMRs in both treatment arms.
The biopsies will be analysed locally and centrally and evaluated according to Banff criteria version 2017 or later.
Time frame: 2, 3, and 5-years after transplantation
The number of graft rejection episodes treated with dialysis will be recorded
Time frame: 2, 3, and 5-years after transplantation
The number of graft rejection episodes treated with plasmapheresis will be recorded
Time frame: 2, 3, and 5-years after transplantation
The number of graft rejection episodes treated with medication will be recorded
Time frame: 2, 3, and 5-years after transplantation
AEs/SAEs suspected to be related to imlifidase treatment in the PAES trial will be recorded from the time of signed informed consent for participation in the trial until the last trial visit.
Time frame: 2, 3, and 5-years after transplantation
The patient's use of immunosuppressive medications will be recorded for both cohorts from the time of signed informed consent for participation in the trial until the last trial visit.
Time frame: 2, 3, and 5-years after transplantation
Information about comorbidities that are medically relevant and registered in the patient' medical record will be collected. Medically relevant comorbidities are infections, malignancy, diabetes mellitus and cardiovascular events.
Time frame: 2, 3, and 5-years after transplantation
The Patient-Reported Outcomes Measurement Information System (PROMIS) Social Health domain "Ability to participate in social roles & activities, PROMIS-SF-8a" will be used as a measure of the patients' health related quality of life.
The questionnaire includes 8 questions about a persons ability to participate in different social activities and there are 5 different answers to choose from for each question: Never/Rarely/Sometimes/Usually/Always
Hansa Biopharma AB
Industry
A Prospective, Post-authorisation Long-term Follow-up Trial of Patients Previously Treated With Imlifidase Prior to Kidney Transplantation, Including a Non-comparative Concurrent Reference Cohort
Acronym: PAES-LTFU
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
