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 |
Chronic Allograft Injury (CAI) is a multi-factorial condition that causes gradual loss of kidney function over time, leading ultimately to end stage renal failure and loss of the transplanted kidney. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063209 |
E.1.2 | Term | Chronic allograft nephropathy |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Investigate the safety and tolerability of repeat dosing with zampilimab in kidney transplant recipients with deteriorating kidney function associated with chronic allograft injury (CAI) |
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E.2.2 | Secondary objectives of the trial |
Evaluate the pharmacokinetics (PK) of Zampilimab when administered as repeat doses intravenous (iv) in kidney transplant recipients with CAI |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Functioning living or deceased donor allograft >=1 year posttransplantation -Baseline (screening) biopsy showing Grade II or III interstitial fibrosis/tubular atrophy (IF/TA) (>=25% IF/TA) -Progressive loss in kidney function observed after the first year posttransplant, defined as an estimated glomerular filtration rate (eGFR) decline of ≥3 mL/min/year for at least 24 months prior to screening, with a minimum of 2 documented measurements per year (minimum of 4 documented measurements in the 24-month period, performed at least 1 month apart) -An eGFR >=30 mL/min/1.73 m^2 for a period of 6 months up to screening -Stable standard of care concomitant medication for 3 months prior to screening -Participant is male or female, >=18 years of age
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E.4 | Principal exclusion criteria |
-Recipient of multi-organ transplant (with the exception of repeated kidney transplant recipients, and/or corneal transplant recipients) -Screening biopsy shows evidence of significant active antibodymediated rejection that may affect the conduct of the study (eg, require change in treatment) according to the Principal Investigator (PI) -Screening biopsy shows evidence of T cell-mediated rejection that may affect the conduct of the study (eg, require change in treatment) according to the PI -Screening biopsy shows evidence of de novo or recurrent glomerular disease that may affect the conduct of the study (eg, require change in treatment) according to the PI -Proteinuria >=1500 mg/g at screening -Participant who has a history of biopsy-proven acute rejection or treatment for suspected acute rejection within 3 months prior to screening -Participant has had major surgery (including joint surgery) within 6 months prior to screening, or has planned surgery within 6 months after the last dose of investigational medicinal product (IMP) -Participant has a current diagnosis of foot ulcer or diagnosis of chronic diabetic ulcer or history of delayed wound healing -Participant has taken concomitant medication |
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of treatment-emergent adverse events (TEAEs)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From Day 1 (Baseline) to the end of Safety Follow-up Visit (up to Day 680) |
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E.5.2 | Secondary end point(s) |
1. Serum concentration of zampilimab 2. Urine concentration of zampilimab |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.- 9. From Day 1 (Baseline) to the end of Treatment Period for Stage 1 (up to Day 365) and from Day 1 to the end of Treatment Period for Stage 2 (up to Day 337) |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Phase 1/Phase 2 study. First Administration in Patients. |
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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 | Yes |
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 |
This is an Investigator-blind and participant-blind study. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
Belgium |
Germany |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 6 |
E.8.9.1 | In the Member State concerned days | 26 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 26 |