An Efficacy and Safety Study of Imlifidase in Treatment of Antibody-Mediated Rejection in Kidney Transplant Patients
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|ClinicalTrials.gov Identifier: NCT03897205|
Recruitment Status : Recruiting
First Posted : April 1, 2019
Last Update Posted : October 17, 2019
The purpose of this study is to investigate how efficiently the study medication imlifidase reduces the amount of donor specific antibodies (DSA) in comparison with plasma exchange (PE) therapy, in patients who have an active antibody mediated rejection (AMR) after recently been kidney transplanted. The purpose is also to investigate and compare safety for these two treatments.
20 patients will be treated with imlifidase and 10 with PE.
|Condition or disease||Intervention/treatment||Phase|
|Kidney Transplant Rejection||Drug: Imlifidase Other: Plasma Exchange||Phase 2|
Antibodies to HLA antigens have a strong correlation with allograft injury and loss. Treatment with imlifidase, PE and immunoabsorption (IA) all aim to reduce antibody levels.
This study will compare the reduction in DSA levels after treatment with imlifidase and PE in patients diagnosed with active AMR (according to Banff 2017 criteria) having at least a 25% rise in serum creatinine compared with last measurement prior to the AMR (Patients with delayed graft function and AMR within 10 days after kidney transplantation can be included regardless of serum creatinine level).
Included patients will be randomized to receive either 1 dose of imlifidase (0.25 mg/kg) or 5-10 sessions of PEs (IA may replace PE at the discretion of the investigator). All patients will receive pulse methylprednisolone for 3 days, starting before the 1st treatment, followed by a tapering schedule with prednisolone/prednisone. The patients will also receive high dose IVIg 3 days after imlifidase treatment or directly after the last PE. In addition a single dose of rituximab will be given 5 days after completed IVIg infusion.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized, Open-Label, Multi-Centre, Active Control, Efficacy and Safety Study of Imlifidase in Eliminating Donor Specific Anti-HLA Antibodies in the Treatment of Active Antibody-Mediated Rejection in Kidney Transplant Patients|
|Actual Study Start Date :||April 30, 2019|
|Estimated Primary Completion Date :||April 2020|
|Estimated Study Completion Date :||September 2020|
Subjects randomized to imlifidase treatment will receive one intravenous dose of imlifidase, 0.25 mg/kg, administered over 15 minutes.
Imlifidase is an IgG degrading enzyme of Streptococcus pyrogenes that cleaves all 4 human subclasses of IgG with strict specificity.
Other Name: HMED-IdeS, IdeS, IgG endopeptidase
Active Comparator: Plasma Exchange
Subjects randomized to plasma exchange (PE) treatment will receive 5-10 sessions of PE, as judged by the investigator. Immunoadsorption (IA) may replace PE, at the discretion of the investigator.
Other: Plasma Exchange
The subject's plasma is removed and discarded and the subject receives replacement donor plasma, albumin, or a combination of albumin and saline. IA may be used instead of PE to the discretion of the investigator. IA is achieved by passing a subject's plasma over columns that bind immunoglobulins (Igs) and then the plasma is passed back to the subject.
- Maximum DSA reduction within 5 days from start of treatment [ Time Frame: Start of treatment until 5 days following start of treatment ]Maximum reduction (%) in the sum of DSAs at any time point during the 5 days following the start of treatment. Only DSAs with a pre-dose MFI ≥1000 will be included in the calculations
- DSA levels up to 180 days after treatment [ Time Frame: Screening until Day 180 ]DSA levels will be assessed at all visits throughout the study.
- HLA-antibodies levels up to 180 days after treatment [ Time Frame: Screening until Day 180 ]HLA-antibodies levels will be assessed at all visits throughout the study.
- eGFR levels up to 180 days after treatment [ Time Frame: Screening until Day 180 ]eGFR as calculated from p-creatinine is a measure of kidney function. P-creatinine/eGFR will be assessed at all visits throughout the study.
- Albumin/creatinine ratio in urine up to 180 days after treatment [ Time Frame: Screening until 180 days after treatment ]The albumine/creatinine ratio in urine is a measure of kidney function. Urine sampling for analysis of albumine and creatinine will be done at all visits throughout the study.
- Proportion of subjects with graft loss within 180 days of treatment [ Time Frame: Screening until Day 180 ]Information on graft loss will be collected throughout the study and proportion of subjects with graft loss will be reported.
- Proportion of subjects with signs of transplant glomerulopathy 180 days after treatment [ Time Frame: Day 180 ]The biopsy collected 180 days after treatment will be analysed for signs of glomerulopathy and proportion of subjects with signs of transplant glomerulopathy will be reported
- Change from baseline in histopathology at day 29 and day 180 after treatment [ Time Frame: Screening, 29 days and 180 days after treatment ]Kidney biopsies will be assessed according to the Banff (2017) criteria pre-dose (screening) and at day 29 and 180.
- Change from baseline in mRNA levels in kidney biopsies at day 29 and day 180 after treatment [ Time Frame: Screening, Day 29 and Day 180 ]Kidney biopsies will be taken at screening, day 29 and 180 and assessed for mRNA levels. Changes from baseline will be presented.
- Safety as evaluated by AEs [ Time Frame: Start of treatment until Day 180 ]Type, frequency and intensity of treatment emergent adverse events (TEAEs) and post-treatment AEs. An AE is regarded as a TEAE if occurring up to Day 29 after start of treatment.
- Number of sessions with PE [ Time Frame: Start of treatment until Day 180 ]The number of PE sessions given throughout the study will be recorded in the CRF
- Proportion of subjects with reduction of total serum IgG following treatment until administration of IVIg [ Time Frame: Start of treatment (Day 1) up to administration of IVIg on Day 4 ]Reduction of total serum IgG is defined as YES if the subject's minimum IgG value at any timepoint following the start of treatment and prior administration of IVIg is less than 5% of the baseline level. Proportion of subjects with a reduction of total serum IgG until administration of IVIg will be reported.
- Proportion of subjects with no intact IgG following treatment until administration of IVIg. [ Time Frame: Start of treatment (Day 1) up to administration of IVIg on Day 4 ]Intact IgG is analysed using SDS-PAGE/western blot. The endpoint is met if no detectable intact IgG is found at any time point following treatment until administration of IVIg.
- DSA functionality determined by C1q or C3d analysis pre- and post-treatment [ Time Frame: Screening until Day 180 ]Analysis of DSA functionality assessed as mean MFI levels will be done at all visits throughout the study.
- PK profile of imlifidase: Cmax [ Time Frame: Start of treatment until Day 15 ]Cmax = Maximum observed plasma concentration of imlifidase following dosing
- PK profile of imlifidase: Tmax [ Time Frame: Start of treatment until Day 15 ]Tmax = Time point for maximum observed plasma concentration of imlifidase following dosing
- PK profile of imlifidase: t1/2 [ Time Frame: Start of treatment until Day 15 ]t1/2 = terminal half-life of imlifidase
- PK profile of imlifidase: AUC [ Time Frame: Start of treatment until Day 15 ]AUC = Area under the imlifidase plasma concentration vs time curve
- PK profile of imlifidase: CL [ Time Frame: Start of treatment until Day 15 ]CL = Clearance of imlifidase
- PK profile of imlifidase: V [ Time Frame: Start of treatment until Day 15 ]V = Volume of distribution
- Proportion of patients with anti-drug antibodies (ADAs) [ Time Frame: Screening until Day 180 ]Samples will be collected and analysed for presence anti-imlifidase IgE and anti-imlifidase IgG throughout the study.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03897205
|Contact: Central Contact||+46 46 16 56 email@example.com|
|The Royal Melbourne Hospital||Recruiting|
|Melbourne, Victoria, Australia, 3050|
|Contact: Peter Hughes +61 393 427 053 Peter.Hughes@mh.org.au|
|Principal Investigator: Peter Hughes, MD|
|Universitätsklinik für Innere Medizin III, Klinische Abteilung für Nephrologie MUW||Recruiting|
|Vienna, Austria, 1090|
|Contact: Georg Böhmig, MD +43 1 40400 43630 firstname.lastname@example.org|
|CHU Grenoble Alpes - Néphrologie, dialyse et transplantation||Recruiting|
|Grenoble, France, 38043|
|Contact: Lionel Rostaing, Professor +33 4 76768945 email@example.com|
|Principal Investigator: Lionel Rostaing, Professor|
|Hôpital Saint-Louis. Service de Néphrologie et Transplantation||Recruiting|
|Paris, France, 75475|
|Contact: Carmen Lefaucheur, MD +33 6 76 60 49 46 firstname.lastname@example.org|
|Principal Investigator: Carment Lefaucheur, MD|
|Hôpital Necker - Service de Néphrologie - Transplantation||Recruiting|
|Paris, France, 75743|
|Contact: Christophe Legendre, Professor +33 1 44 49 54 32 email@example.com|
|Principal Investigator: Christophe Legendre, Professor|
|Study Director:||Elisabeth Sonesson, PhD||Hansa Biopharma AB|