Kidney Transplant RejectionNCT04711850
An Long-term Follow-up Trial of Kidney Tx Patients Treated With Imlifidase or PE After an AMR
An observational study of Kidney Transplant Rejection, run by Hansa Biopharma AB at 7 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplant Rejection
- What is being tested?
- Imlifidase
- How many people
- 18 participants
- Where
- 7 sitesin 3 countries
- Study dates
- 20 Jan 2021to 30 Mar 2023
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients who have been treated with imlifidase or plasma exchange in the feeder study 16-HMedIdeS-12 may be included.
Who may be able to join
- 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.
Who cannot join
- Inability by the judgement of the investigator to participate in the trial for any other reason
Trial locations and contacts
7 sites in 3 countries.
7 sites in 3 countries
France4 sites
Hôpital Pellegrin
Bordeaux, 33076
CHU Grenoble Alpes - Néphrologie, dialyse et transplantation
Grenoble, 38043
Hôpital Saint-Louis. Service de Néphrologie et Transplantation
Paris, 75475
Hôpital Necker - Service de Néphrologie - Transplantation
Paris, 75742
Germany2 sites
Charité-Universitätsmedizin. Dept. of Nephrology and Medical Intensive Care
Berlin, 13353
Medizinische Hochschule Hannover
Hanover
Austria1 site
Universitätsklinik für Innere Medizin III, Klinische Abteilung für Nephrologie MUW
Vienna, 1090
About this study
Official title: 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
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.
Read the 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
- Being tested
- Imlifidase
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImlifidaseDrug
Also called IdeS, HMED-IdeS
Immunoglobulin G degrading enzyme of Streptococcus pyogenes
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Imlifidase | |
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Graft Survival at Year 3
Graft survival is defined as time from start of AMR treatment in feeder study (16-HMedIdeS-12) to graft loss. Graft loss is defined as permanent return to dialysis for at least 6 weeks, re-transplantation, or nephrectomy.
Data table show number of patients with a functioning graft at Year 3.
Measured: 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12)
Secondary outcomes (9)
Overall Graft Survival at Year 2
Graft survival is defined as time from start of AMR treatment in feeder study (16-HMedIdeS-12) to graft loss. Graft loss is defined as permanent return to dialysis for at least 6 weeks, re-transplantation, or nephrectomy.
Measured: 2 years after start of AMR treatment in feeder study (16-HMedIdeS-12)
Overall Graft Survival at Year 1
Graft survival is defined as time from start of AMR treatment in feeder study (16-HMedIdeS-12) to graft loss. Graft loss is defined as permanent return to dialysis for at least 6 weeks, re-transplantation, or nephrectomy.
Measured: 1 year after start of AMR treatment in feeder study (16-HMedIdeS-12)
Patient Survival at Year 3
Overall patient survival is defined as time from start of AMR treatment in feeder study (16-HMedIdeS-12) to death for any cause.
Measured: 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12)
Kidney Function as Evaluated by eGFR
Estimated glomerular filtration rate (eGFR) was calculated as described by the Modification of Diet in Renal Disease Study (MDRD) equation. eGFR is a measure of kidney function. eGFR for a kidney with normal function is 90 mL/min/1.72m2. Kidney disease is characterised by a decreased eGFR value.
Measured: 1, 2 and 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12)
Kidney Function as Evaluated by S/P-creatinine
S/P-creatinine is a measure of kidney function. Kidney disease is characterized by an increased S/P-creatinine level.
Measured: 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
Information about rejection episodes will be collected, according to Banff 2017 or later classification. For-cause biopsies together with contemporaneous local DSA analyses, kidney function parameters (creatinine, albumin/creatinine ratio in urine) and treatments (e.g. plasma exchange and IVIg) will be collected to assess the rejection episodes.
Measured: 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)
Information about rejection episodes will be collected, according to Banff 2017 or later classification. For-cause biopsies together with contemporaneous local DSA analyses, kidney function parameters (creatinine, albumin/creatinine ratio in urine) and treatments (e.g. plasma exchange and IVIg) will be collected to assess the rejection episodes.
Measured: 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12)
DSA Levels
DSA levels will be measured using single antigen bead human leukocyte antigen (SAB-HLA) assay
Measured: 1, 2 and 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12)
ADA Levels
The immunogenicity of imlifidase will be assessed by measuring ADA levels.
Measured: 1,2 and 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2021
- Study start20 Jan 2021
- Primary completion30 Mar 2023
- Study completion30 Mar 2023
Why it stopped: This is an internal decision based on prioritisations and no safety issues have been raised during the trial.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Kidney Transplant RejectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hansa Biopharma AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Operations, Study director, Hansa Biopharma AB
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04711850
- Sponsor's protocol ID
- 20-HMedIdes-18
- Other IDs
- 2020-004777-49
- Status last verified
- May 2025
- First submitted
- 13 Jan 2021
- Last updated
- 28 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39023092
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04711850
- Acronym / sponsor ID
- 20-HMedIdes-18
- Conditions
- Kidney Transplant Rejection
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: This is an internal decision based on prioritisations and no safety issues have been raised during the trial.
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Hansa Biopharma ABIndustry (pharma, biotech, devices)
- Study start
- 20 Jan 2021 (actual)
- Primary completion
- 30 Mar 2023 (actual)
- Study completion
- 30 Mar 2023 (actual)
- First posted
- 15 Jan 2021 (actual)
- Results
- Posted 11 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Imlifidase treatment in feeder Study 16-HMedIdeS-12 | – | Drug: ImlifidaseNo 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. |
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who have been treated with imlifidase or plasma exchange in the feeder study 16-HMedIdeS-12 may be included.
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (1 listed)
- Inability by the judgement of the investigator to participate in the trial for any other reason
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ImlifidaseAlso: IdeS, HMED-IdeSImmunoglobulin G degrading enzyme of Streptococcus pyogenes | Drug | Imlifidase treatment in feeder Study 16-HMedIdeS-12 |
Primary outcome
Overall Graft Survival at Year 3
Time frame: 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12)
Graft survival is defined as time from start of AMR treatment in feeder study (16-HMedIdeS-12) to graft loss. Graft loss is defined as permanent return to dialysis for at least 6 weeks, re-transplantation, or nephrectomy. Data table show number of patients with a functioning graft at Year 3.
9 secondary outcomes
Overall Graft Survival at Year 2
Time frame: 2 years after start of AMR treatment in feeder study (16-HMedIdeS-12)
Overall Graft Survival at Year 1
Time frame: 1 year after start of AMR treatment in feeder study (16-HMedIdeS-12)
Patient Survival at Year 3
Time frame: 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12)
Kidney Function as Evaluated by eGFR
Time frame: 1, 2 and 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12)
Kidney Function as Evaluated by S/P-creatinine
Time frame: 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
Time frame: 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)
Time frame: 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12)
DSA Levels
Time frame: 1, 2 and 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12)
ADA Levels
Time frame: 1,2 and 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39023092Halleck 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Operations study director
Hansa Biopharma AB
7 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Kidney Transplant Rejection, run by Hansa Biopharma AB at 7 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in France, Germany, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Graft Survival at Year 3 (time frame: 3 years after start of AMR treatment in feeder study (16-HMedIdeS-12)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04711850, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2025.