E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Graft versus host disease |
la enfermedad de injerto-contra-huésped |
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E.1.1.1 | Medical condition in easily understood language |
Graft-versus-host disease is a complication that frequently occurs following hematopoietic cell transplantation when the transplanted cells attack the patients’ organs leading to organ damage. |
la enfermedad de injerto-contra-huésped es una complicación que ocurre frecuentemente despues de un transplante de celulas hamatopoyéticas estas dañan los organos del paciente |
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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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018651 |
E.1.2 | Term | Graft versus host disease |
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 |
To evaluate the efficacy of AAT at the selected dose for the prevention of acute GVHD following HCT. |
Evaluar la eficacia de la AAT a la dosis seleccionada para la prevención de la EICH aguda tras un THB. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the efficacy of AAT, including the prevention of post-hematopoietic cell transplant complications. 2. To evaluate the safety of AAT, based on incidence of systemic infections and related adverse events. 3. To evaluate the pharmacokinetics of AAT in HCT recipients. |
1.Evaluar la eficacia de la AAT, incluida la prevención de las complicaciones posteriores al THB. 2.Evaluar la seguridad de la AAT tomando como base la incidencia de infecciones sistémicas y acontecimientos adversos (AA) relacionados. 3.Evaluar la FC de la AAT en los receptores de THB. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subjects, ≥12 years of age, undergoing HCT for hematological malignancies, including leukemia, lymphoma and multiple myeloma 2. Planned myeloablative conditioning regimen |
1.Sujetos de sexo masculino o femenino, ≥12 años y sometidos a un THB para el tratamiento de neoplasias hematológicas como la leucemia, el linfoma y el mieloma múltiple. 2.Pauta de acondicionamiento mieloablativo prevista |
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E.4 | Principal exclusion criteria |
1. Prior autologous or allogeneic HCT 2. T-cell depleted transplant or planned use of anti-T cell antibody therapy either ex vivo or in vivo 3. Planned umbilical cord blood (UCB) transplant |
1.THB autólogo o alógeno anterior. 2.Trasplante con reducción de linfocitos T o uso previsto de un tratamiento con anticuerpos antilinfocitos T ex vivo o in vivo (p. ej., globulina antitimocítica [GAT], alemtuzumab) durante el estudio. 3.Trasplante de sangre del cordón umbilical previsto. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent of subjects with acute graft-versus-host-disease-free survival |
la incidencia de la supervivencia sin enfermedad injerto contra huésped aguda |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
180 days post-hematopoietic cell transplantation |
a los 180 días del THB. |
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E.5.2 | Secondary end point(s) |
-Percent of subjects with Grade II-IV acute GVHD -Percent of subjects with Grade III-IV acute GVHD -Number of subjects with all-cause mortality -Percent of subjects with Grade II aGVHD -Percent of subjects with Grade III aGVHD -Percent of subjects with Grade IV aGVHD -Time to all-cause mortality -Time to non-relapse mortality -Percent of subjects with moderate-to-severe chronic GVHD -Percent of subjects with discontinuation of immune suppression -Time to neutrophil engraftmen -Time to GVHD relapse-free survival -Percent of subjects with relapse of primary malignancies -Percent of subjects with systemic infections -Percent of subjects with study drug related adverse events -Maximum concentration (Cmax) of AAT -Area under the concentration curve (AUC) for AAT -Clearance (CL) of AAT -Volume of distribution (V) for AAT |
•180 y en los 365 días posteriores al Incidencia de EICHa de grado II-IV en los 100 y en los 180 días posteriores al THB •Incidencia de EICHa de grado III-IV en los 100 y en los 180 días posteriores al THB •Mortalidad por cualquier causa a los 180 y a los 365 días del THB •Incidencia de EICH de grados II, III o IV en los 100 y en los 180 días posteriores al THB •Tiempo transcurrido hasta la muerte por cualquier causa •Tiempo transcurrido hasta la muerte sin recaída •Incidencia de EICH crónica de moderada a grave en los 180 y en los 365 días posteriores al THB •Incidencia de la interrupción de la inmunodepresión en los 180 y en los 365 días posteriores al THB •Tiempo hasta la aceptación del injerto de neutrófilos •Supervivencia sin recaída de la EICH tras más de 365 días desde el THB •Incidencia de recaídas de las neoplasias malignas principales en los THB •Incidencia de infecciones sistémicas a los 60 y a los 180 días del THB •Incidencia de AA relacionados con el fármaco del estudio •Parámetros de FC, incluidos la concentración máxima (Cmáx), el área bajo la curva (ABC)0-t, las concentraciones mínimas (Cmín), el aclaramiento, el volumen de distribución (V) y otros, según resulte necesario |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-Within 100 and 180 days post-HCT -Within 100 and 180 days post-hematopoietic cell transplant (HCT) -Within 180 and 365 days post-HCT -Within 100 and 180 days post-HCT -Within 100 and 180 days post-HCT -Within 100 and 180 days post-HCT -Up to 365 days post-HCT -Up to 365 days post-HCT -Within 180 and 365 days post-HCT -Within 180 and 365 days post-HCT -Up to 365 days post-HCT -Up to 365 days post-HCT -Within 180 and 365 days post-HCT -At Days 60 and 180 post-HCT -Up to 365 days post-HCT -Before and up to 72 after infusion of AAT -Before and up to 72 after infusion of AAT -Before and up to 72 after infusion of AAT |
-Entre 100 y 180 dias post-THB -Entre 100 y 180 días post-THB -Entre 180 y 365 días post-THB -Entre 100 y 180 días post-THB -Entre100 y 180 días post- THB -Entre 100 y 180 días post-THB -Hasta 365 días post-THB -Hasta 365 días post-THB -Entre 180 y 365 días post-THB -Entre 180 y 365 días post-THB -Hasta 365 días post-THB -Up to 365 days post-HCT -entre 180 y 365 días post-THB -A los 60 and 180 días post-THB -Hasta 365 días post-THB -Antes y hasta 72 días despues de la infusion AAT -Antes y hasta 72 días despues de la infusion AAT -Antes y hasta 72 días despues de la infusion AAT -Antes y hasta 72 días despues de la infusion AAT |
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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 | No |
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) | 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 |
Sequential: Subjects receive interventions after reaching prior milestones, eg dose escalation stud. |
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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 | 5 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 |
Belgium |
Canada |
France |
Germany |
Hungary |
Italy |
Poland |
Spain |
Sweden |
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 | 4 |
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 | 4 |