E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Antibody-mediated rejection in kidney transplant patients |
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E.1.1.1 | Medical condition in easily understood language |
Rejection caused by antibodies in kidney transplant patients |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10023439 |
E.1.2 | Term | Kidney transplant rejection |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Investigate the efficacy of imlifidase compared with PE in removal of DSA in patients who are experiencing an active AMR episode after kidney transplantation |
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E.2.2 | Secondary objectives of the trial |
• 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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 or chronic 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
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E.4 | Principal 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 such as severe immune deficiency and severe cardiac insufficiency (New York Heart Association (NYHA) Class IV) or severe uncontrolled heart disease 8. Known allergy/sensitivity to imlifidase, IVIg and/or rituximab and the respective excipients 9. Patient unable to tolerate treatment with plasmapheresis or immunoadsorption, as judged by the investigator 10. Unsuitable to participate in the study for any other reason as judged by the investigator 11. Positive PCR test for SARS-CoV-2 virus infection 12. Current diagnosis or history of thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP |
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E.5 End points |
E.5.1 | Primary end point(s) |
Maximum reduction in mean DSA level at any time point during the 5 days following the start of treatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
• DSA levels will be evaluated pre-dose, at 2, 6, 24, 48, 72, and 96 hours |
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E.5.2 | 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)
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
France |
Germany |
Sweden |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |