E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Refractory AMR in adult renal transplant participants |
Rechazo refractario mediado por anticuerpos en receptores adultos de n trasplante renal |
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E.1.1.1 | Medical condition in easily understood language |
Antibody-mediated kidney transplant rejection |
Rechazo de trasplante renal mediado por anticuerpos |
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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. |
El objetivo principal del estudio es evaluar la eficacia de C1-INH en el tratamiento del RMA refractario en receptores de aloinjertos renales |
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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. |
Los objetivos secundarios del estudio son: 1. Evaluar la eficacia de C1-INH en el tratamiento del RMA refractario en receptores de aloinjertos renales. 2. Evaluar la seguridad de C1-INH en el tratamiento del RMA refractario en receptores de aloinjertos renales. 3. Evaluar la farmacocinética de C1-INH en el tratamiento del RMA refractario en receptores de aloinjertos renales |
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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 OR for patients diagnosed with delayed graft function (DGF), a 50% increase in urine output with a 50% decrease in serum creatinine over the first 7 days post-transplant without dialysis; 5) Acute AMR. |
1) Hombre o mujer de al menos 18 años de edad; 2) Evidencia de al menos un anticuerpo específico del donante (AED DSA); 3) Receptor de un trasplante de riñón; 4) Alcanzar un estado estable con una tasa de filtración glomerular (eGFR) posterior al trasplante que sea ≥ 40 mL / min / 1,73 m2, ó para los pacientes diagnosticados con retraso de la función del injerto (DGF), un incremento del 50% en la producción de orina con un descenso del valor de la creatinina sérica del 50% durante los primeros 7 días posteriores al trasplante sin diálisis. 5) Rechazo agudo mediado por anticuerpos |
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E.4 | Principal exclusion criteria |
1) Recipient of an en bloc kidney transplant; 2) Recipient of a kidney transplant ABO incompatible donor without evidence of DSA; 3) Current active hepatitis C virus (HCV) infection; 4) Active bacterial or fungal infection; 5) Ongoing dialysis >2 weeks; 6) Known congenital bleeding or coagulopathy disorder; 7) Current cancer or a history of cancer; 8) Female subjects who are pregnant or breast feeding; 9) Male or female subjects who are unwilling to use contraception or who are not surgically sterile. |
1) Receptor de un trasplante de riñón en bloque; 2) Receptor de un donante incompatible de trasplante de riñón ABO, sin evidencia de pruebas de Anticuerpos específicos del donante (AED) 3) Infección activa del virus de la hepatitis C 4) Infección bacteriana o fúngica activa; 5) Diálisis continua> 2 semanas; 6) Trastornos congénitos conocidos de sangrado o coagulopatía; 7) Cáncer actual o antecedentes de cáncer; 8) Mujeres embarazadas o en período de lactancia; 9) Hombres o mujeres que no estén dispuestos a usar anticonceptivos o que no se han sometido a procesos quirúrgicos de esterilidad. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to loss of response during Treatment Period 2 |
Tiempo de pérdida de respuesta durante el Periodo de Tratamiento 2. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to approximately 25 weeks |
Hasta aproximadamente 25 semanas. |
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E.5.2 | Secondary end point(s) |
- Time to all-cause allograft failure after randomization into Treatment Period 2 - Percentage of subjects with response to treatment at the end of Treatment Period 1 - Percentage of subjects with sustained improvement of eGFR during Treatment Period 2. - Change from screening in Banff category scores at up to 38 weeks - Percentage of subjects with new or worsening chronic active AMR during Treatment Period 2 - Percentage of subjects with splenectomy during Treatment Period 1 and during Treatment Period 2 - Percentage of subjects surviving at the end of Treatment Period 2 - Percentage of subjects with a surviving allograft at the end of Treatment Period 2 - Time to subject death after randomization into Treatment Period 2 - Percentage of subjects with any adverse event (AE) assessed as related to investigational product |
- Tiempo transcurrido hasta el fracaso del aloinjerto, por cualquier causa, tras la aleatorización en el Periodo de tratamiento 2 - Porcentaje de sujetos con respuesta al tratamiento al final de Período de tratamiento 1 - Porcentaje de sujetos con mejoría sostenida de la TFGe durante el Período de tratamiento 2. - Cambio en las puntuaciones de la categoría de Banff desde la inclusión hasta 38 semanas - Porcentaje de sujetos con aparición o empeoramiento de un RMA crónico activo durante el período de tratamiento 2 - Porcentaje de sujetos con esplenectomía durante el período de tratamiento 1 y durante el período de tratamiento 2 - Porcentaje de sujetos que sobreviven al final del período de tratamiento 2 - Porcentaje de sujetos con supervivencia del aloinjerto al final del Período de tratamiento 2 - Tiempo transcurrido hasta el fallecimiento del sujeto después de la aleatorización en el período de tratamiento 2 - Porcentaje de sujetos con cualquier evento adverso (AE) evaluado como relacionado con el producto de investigación |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Up to approximately 195 weeks - Up to approximately 13 weeks - Up to approximately 25 weeks - Screening and up to approximately 38 weeks - Up to approximately 25 weeks - Up to approximately 38 weeks - Up to approximately 38 weeks - Up to approximately 38 weeks - Up to approximately 195 weeks - Up to approximately 42 weeks after the time of first investigational product administration |
- Hasta aproximadamente 195 semanas - Hasta aproximadamente 13 semanas - Hasta aproximadamente 25 semanas - Selección y hasta aproximadamente 38 semanas - Hasta aproximadamente 25 semanas - Hasta aproximadamente 38 semanas - Hasta aproximadamente 38 semanas - Hasta aproximadamente 38 semanas - Hasta aproximadamente 195 semanas - Hasta aproximadamente 42 semanas ttras la primera administración del PI |
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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
| 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 | 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 |
Australia |
Canada |
European Union |
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 | 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 |