E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Refractory AMR in adult renal transplant participants |
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E.1.1.1 | Medical condition in easily understood language |
Antibody-mediated kidney transplant rejection
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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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to evaluate the efficacy of C1-INH in the treatment of refractory AMR in renal allograft recipients.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are: 1. To evaluate the efficacy of C1-INH in the treatment of refractory AMR in renal allograft recipients. 2. To evaluate the safety of C1-INH in the treatment of refractory AMR in renal allograft recipients. 3. To evaluate the pharmacokinetics of C1-INH during the treatment of refractory AMR in renal allograft recipients.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Male or female at least 18 years of age; 2) Evidence of at least one donor-specific antibody (DSA); 3) Recipient of a kidney transplant; 4) Achieved a steady-state, post-transplant eGFR ≥ 40 mL/min/1.73 m2 within 60 days of post-transplant OR a 50% increase in urine output with a 50% decrease in serum creatinine over the first 7 days posttransplant in subjects with slow or delayed graft function; 5) Acute AMR. |
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E.4 | Principal exclusion criteria |
1) Recipient of an en bloc kidney transplant; 2) Current active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection ; 3) Active bacterial or fungal infection; 4) Ongoing dialysis >2 weeks; 5) Known congenital bleeding or coagulopathy disorder; 6) Current cancer or a history of cancer; 7) Female subjects who are pregnant or breast feeding; 8) Male or female subjects who are unwilling to use contraception or who are not surgically sterile.
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects with loss-of-response at the end-of- Treatment Period 2 (TP2)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to approximately 25 weeks
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E.5.2 | Secondary end point(s) |
- Proportion of subjects with all-cause allograft failure through the Follow-up Period (ie, within 48 months after enrollment) - The difference between the end-of-TP1 eGFR and baseline eGFR - The difference between the end-of-TP2 eGFR and the end-of-TP1 eGFR - The rate of change of eGFR during TP2 as defined by the slope of the mean regression of eGFR over time in TP2 - Time (days) to all-cause allograft failure through the Follow up Period (ie, within 48 months after enrollment) - Proportion of responders at the end-of-Treatment Period 1 - Proportion of subjects surviving through the Follow-up Period - Proportion of subjects with any adverse event (AE) assessed as related to investigational product - Mean pre-dose C1-esterase inhibitor functional activity - Time to maximum plasma concentration (Cmax) for C1-INH functional activity - Area under the plasma concentration time curve (AUC0-t) for C1-INH functional activity |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Up to approximately 208 weeks - Up to approximately 13 weeks - Up to approximately 25 weeks - Screening and up to approximately 38 weeks - Up to approximately 208 weeks - Up to approximately 13 weeks - Up to approximately 208 weeks - Up to approximately 42 weeks after the time of first investigational product administration - Day 1, Week 12, and Week 38 - Up to 72 hours after dose - Up to 72 hours after dose
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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 | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
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) | 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
| 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 | 14 |
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 |
United States |
European Union |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |