E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Adult patients that receive kidney from another person |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
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 |
Cohort 1: to demonstrate that two CFZ533 dosing regimens are superior to a tacrolimus-based regimen with respect to the iBox risk prediction score at 12 months posttransplantation.
Cohort 2: To demonstrate that CFZ533 dosing regiment is superior to a tacrolimus-based regimen with respect to iBox risk prediction score at 12 months post conversion. |
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E.2.2 | Secondary objectives of the trial |
To demonstrate that two CFZ533 dosing regimens are superior to a TAC based regimen with respect to the mean estimated glomerular filtration rate (eGFR) over 12 months post-transplantation in de novo patients (cohort 1).
To demonstrate that two CFZ533 dosing regimens are non-inferior to the TAC based regimen with respect to the proportion of patients who experience the composite efficacy failure event (BPAR, Graft Loss or Death) over 12 months posttransplantation (cohort 1).
To demonstrate that CFZ533 is superior to a TAC-based regimen with respect to the mean change in eGFR from baseline to 12 months post conversion in maintenance patients (cohort2).
To demonstrate that CFZ533 dosing regimen is non-inferior to the TAC based regimen with respect to the proportion of patients who experience the composite efficacy failure event (BPAR, Graft Loss or Death) over 12 months post-conversion (cohort 2).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male or female patient ≥ 18 years old.
2. Up to date vaccination
3.Recipients of a primary kidney transplant from a brain-dead donor (DBD), living unrelated or non-HLA identical living related donor (cohort1).
4.Recipients of a kidney with a cold ischemia time (CIT) < 24 hours (cohort 1)
5. Recipients of a primary graft received 6 to 24 months prior enrollment, on a regimen containing Tac+MMF±CS (Cohort 2)
6.Patients with an actual eGFR ≥ 45 mL/min/1.73m2 (Cohort 2) |
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E.4 | Principal exclusion criteria |
1.Multi-organ transplant recipients or prior kidney transplant (cohort 1 and 2)
2.Pregnant or nursing women (cohort 1 and 2)
3.Women of child bearing potential unless using highly effective methods of contraception during dosing and 12 weeks after study medication has been stopped (cohort 1 and 2)
4. Recipients of an organ from a donor after cardiac death (DCD) (cohort 1).
5. Recipient of an organ from an HLA identical living related donor (cohort 1).
6. Recipients of kidneys from donors who are older than 65 years (cohort 1).
7.Patients at high immunological risk for rejection (cohort 1)
8.DSA within 12 weeks prior enrollment (cohort 2)
9. Ongoing rejection or rejection that required treatment within 12 weeks prior enrollment (cohort 2)
10. Severe humoral and/or cellular rejection (BANFF ≥ IIb) before enrollment (cohort 2) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Cohort 1:
Mean iBox risk prediction score at 12 months post-transplantation
Cohort 2:
Mean iBox risk prediction score at month 12
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
-at 12 months from enrollment(cohort 1 and 2) |
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E.5.2 | Secondary end point(s) |
-Mean eGFR at 12 months posttransplantation (Cohort 1)
- Proportion of patients with composite event (BPAR, Graft Loss or Death) over 12 months post-transplantation (Cohort 1)
-Mean change in eGFR from baseline to 12 months post conversion (Cohort 2).
-Proportion of patients with composite event (BPAR, Graft Loss or Death) over 12 months post conversion.
-Proportion of patients with AEs, SAEs, AEs of special interest (cohort 1 and 2)
-Free CFZ533 plasma concentrations over time (cohort 1 and 2)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-at 12 months post-enrollment
-at 12 months post-enrollment
-at 12 months post-enrollment
-at 12 months post-enrollment
-continuously
-continuously
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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 | Yes |
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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
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 | 59 |
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 |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
Croatia |
Czech Republic |
Estonia |
France |
Germany |
Hungary |
Italy |
Japan |
Korea, Republic of |
Latvia |
Lithuania |
Netherlands |
Norway |
Russian Federation |
Slovakia |
Spain |
Sweden |
Switzerland |
United Kingdom |
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 | 5 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 4 |