Antibody-mediated rejection in kidney transplant patients MedDRA version: 20.0 Level: PT Classification code 10023439 Term: Kidney transplant rejection System Organ Class: 10021428 - Immune system disorders
Conditions
Sponsors
Hansa Medical AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed Informed Consent obtained before any study-related procedures 2. Willingness and ability to comply with the protocol 3. Male and/or female donor kidney recipients age =18 years at the time of screening 4. Presence of DSA(s) 5. Meet the Banff 2017 criteria for active AMR 6. At least 25% rise in serum creatinine compared to last individual value taken prior to the AMR. Patients with delayed graft function and AMR within 10 days after transplant (confirmed by kidney biopsy) can be included regardless of serum creatinine level 7. Women of child-bearing potential willing or able to use at least one highly effective contraceptive method throughout the study. In the context of this study, an effective method is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly such as: • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; oral, intravaginal, transdermal • progestogen-only hormonal contraception associated with inhibition of ovulation; oral, injectable, implantable • intrauterine device (IUD) • intrauterine hormone-releasing system (IUS) • bilateral tubal occlusion • vasectomised partner • true abstinence: When this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception] 8. Men willing to use double-barrier contraception from the first day of treatment until at least 2 months after the dose of imlifidase, if not abstinent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Previous treatment with imlifidase 2. Previous high dose IVIg treatment (2 g/kg) within 28 days prior to inclusion 3. Lactating or pregnant females 4. Significantly abnormal general serum screening lab results judged inappropriate for inclusion in the study by the investigator 5. Intake of other investigational drugs within 5 half-lives (or similar) of the product prior to inclusion 6. Clinically relevant active infection(s) as judged by the investigator 7. Any condition that in the opinion of the investigator could increase the subject’s risk by participating in the study 8. Known allergy/sensitivity to IVIg and/or rituximab 9. Unsuitable to participate in the study for any other reason as judged by the investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Investigate the efficacy of imlifidase compared with PE in removal of DSA in patients who are experiencing an active AMR episode after kidney transplantation;Secondary Objective: • Evaluate DSA levels up to 180 days after treatment • Evaluate HLA-antibodies levels up to 180 days after treatment • Evaluate the overall kidney function up to 180 days after treatment • Investigate the occurrence of AMR up to 180 days after treatment • Investigate the safety and tolerability of imlifidase compared to PE in patients experiencing active AMR episodes • Evaluate the number of PE-sessions needed • Evaluate the pharmacokinetics, pharmacodynamics and immunogenicity of imlifidase ;Primary end point(s): Maximum reduction in mean DSA level at any time point during the 5 days following the start of treatment ;Timepoint(s) of evaluation of this end point: • DSA levels will be evaluated pre-dose, at 2, 6, 24, 48, 72, and 96 hours | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • DSA levels up to 180 days after treatment • Kidney function change from baseline (at screening) as evaluated by eGFR, P creatinine and albumin/creatinine ratio in urine up to 180 days after treatment • Proportion of subjects with graft loss within 180 days of treatment • Signs of transplant glomerulopathy 180 days post treatment • Change from baseline (at screening) in histopathology per Banff Criteria at 29 and 180 days • Type, frequency and intensity of adverse events • DSA functionality determined by C1q or C3d analysis pre- and post-treatment • Presence of ADA (anti-imlifidase IgG) ;Timepoint(s) of evaluation of this end point: • DSA levels will be evaluated on day 6, 8, 11, 15, 22, 29, 64, 90, and 180 • Kidney function will be measured predose, at 24, 48, 72, and 96 hours, and at day 6, 8, 11, 22, 29, 64, 90 and 180 • Kidney biopsies will be performed pre-dose and on day 29 and 180 • Safety parameters pre-dose, at 24, 48, 72, and 96 hours, and at day 6, 8, 11, 15, 22, 29, 64 and 90 • DSA functionality (C1q or C3d) will be evaluated at multiple timepoint up to day 180 • Pharmacodynamic profile will be measured up to 180 days after start of treatment | — |
Countries
Australia, Austria, France, Germany, Sweden, United States
Contacts
Public ContactClinical contact information
Hansa Medical AB
Outcome results
None listed