E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of Bronchiolitis Obliterans Syndrome in lung transplant |
Prevención del síndrome de bronquiolitis obliterante en pacientes con trasplante pulmonar |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of the destruction of lung tissue after a lung transplant |
Prevención del síndrome de bronquiolitis obliterante en pacientes con trasplante pulmonar |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049202 |
E.1.2 | Term | Bronchiolitis obliterans |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal 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 objective of the study is to evaluate the long-term safety of L-CsA in prevention of bronchiolitis obliterans syndrome (BOS) following lung transplantation (LTx) in patients previously enrolled in phase II/III L-CsA clinical trial 12011.201. |
Evaluar la seguridad a largo plazo de L-CsA en la prevención del síndrome de bronquiolitis obliterante (SBO) tras un trasplante de pulmón (TP) en pacientes previamente incluidos en el ensayo clínico de fase II/III con L-CsA, 12011.201 |
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E.2.2 | Secondary objectives of the trial |
In addition, the long-term efficacy outcome over a maximum of three years will be determined. |
Determinar el resultado de eficacia a largo plazo durante un máximo de tres años |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Patient has completed the L-CsA clinical trial 12011.201 2.Patient is capable of understanding the purpose and risks of the follow-up study, has been fully informed and has given written informed consent to participate in the study 3.Female patients of child bearing potential must test negative on standard urine pregnancy test prior to continuation and must agree to practice effective birth control during the study(see Appendix 3) 4.Estimated life expectancy > 6 months 5.Capable of self-administration of medications 6.Patient has stable creatinine levels |
Criterios de inclusión 1.El paciente ha completado el ensayo clínico 12011.201 con L-CsA 2.El paciente es capaz de entender el objetivo y los riesgos del estudio de seguimiento, ha sido completamente informado y ha otorgado su consentimiento informado por escrito para participar en el estudio 3.Las mujeres en edad fértil deben obtener un resultado negativo en una prueba de embarazo estándar en orina antes de continuar y deben aceptar utilizar anticonceptivos eficaces durante el estudio (ver Anexo 3) 4.Esperanza de vida estimada >6 meses 5.Capaz de autoadministrarse los medicamentos 6.El paciente tiene niveles de creatinina estables |
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E.4 | Principal exclusion criteria |
1.Patients with ongoing irreversible L-CsA related serious adverse events 2.Patients with known hypersensitivity for ciclosporin A 3.Patient intends to participate in another IMP clinical trial other than listed in the inclusion criteria 4.Patient receives mechanical ventilation 5.Patients underwent pulmonary re-transplantation 6.Patient is a pregnant or breast-feeding woman 7.Patient is unlikely to comply with visits, inhalation procedures or spirometric measurements scheduled in the protocol 8.Patient receives any systemic or topical Rosuvastatin 9.Patient has been previously enrolled in this study 10.Patient with malignancy diagnosed during study 12011.201 (with the exception of skin cancer) 11.Documented respiratory infections unless on appropriate antimicrobial therapy with evidence of clinical response 12.Patient is not eligible to continue IMP inhalation according to the Investigator?s discretion |
1.Pacientes con acontecimientos adversos graves en curso e irreversibles asociados a la L-CsA 2.Pacientes con hipersensibilidad conocida a la ciclosporina A 3.Paciente con intención de participar en otro ensayo clínico con un PEI a excepción de los enumerados en los criterios de inclusión 4.Paciente recibe ventilación mecánica 5.Pacientes sometidos a retrasplante de pulmón 6.Paciente embarazada o en periodo de lactancia 7.Paciente con poca probabilidad de cumplir con las visitas, los procedimientos de inhalación o las determinaciones espirométricas previstos en el protocolo 8.Paciente recibe rosuvastatina sistémica o tópica 9.Paciente previamente incluido en este estudio 10.Paciente con una neoplasia maligna diagnosticada durante el estudio 12011.201 (a excepción de cáncer de piel) 11.Infecciones respiratorias documentadas, a menos que reciba tratamiento antimicrobiano apropiado y muestre indicios de una respuesta clínica 12.Paciente no elegible para continuar con la inhalación del PEI a juicio del investigador |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety Endpoints: Safety will be assessed using the following parameters: ?Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (from inclusion into the 12011 203 study) ?Laboratory evaluations (chemistry, haematology and urinalysis) will be performed as scheduled by the local institution. Only abnormal and clinically relevant values will be recorded when they are reported ?Overall rate of mortality ?Vital signs ?Trough L-CsA and tacrolimus blood levels |
Criterios de valoración de la seguridad: La seguridad se evaluará utilizando los siguientes parámetros: Acontecimientos adversos (AA) y acontecimientos adversos graves (AAG) emergentes del tratamiento ?Se realizarán evaluaciones de laboratorio (bioquímica, hematología y urinálisis) de la forma prevista por el centro local. Solo se registrarán los valores anormales y clínicamente relevantes cuando se notifiquen ?Tasa global de mortalidad ?Constantes vitales ?Niveles mínimos de L-CsA y tacrolimus en sangre |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety end-points will be evaluated throught the duration of the study. |
Los criterios de valoración de la seguridad se evaluarán durante la duración del estudio. |
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E.5.2 | Secondary end point(s) |
Efficacy Endpoints: Bronchiolitis obliterans syndrome (BOS): ?BOS-free survival ?Incidence of BOS ?Pulmonary function |
Criterios de valoración de la eficacia: Síndrome de bronquiolitis obliterante (SBO): ?Supervivencia libre de SBO ?Incidencia de SBO ?Función pulmonar |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy will be assessed using the following parameters: ?Time to occurrence of BOS (? grade 1), respectively BOS progression over the following time period ?Period of time starting from inclusion into study 12011.201 (Phase II/III) until occurrence of BOS ? grade 1, or death, or re-transplantation Incidence of BOS (until end of study): ?Number and severity of BOS episodes from inclusion until end of study 12011.203 (Safety follow-up) Pulmonary Function Tests (PFT) (at each clinic visit): ?Forced Expiratory Volume in one second (FEV1). ?Forced Midexpiratory Flow (FEF25-75) |
Se evaluará la eficacia utilizando los siguientes parámetros: Tiempo hasta la aparición de SBO (? grado 1) y progresión de SBO durante el siguiente periodo de tiempo, respectivamente ?Periodo de tiempo desde la inclusión en el estudio 12011.201 (fase II/III) hasta la aparición de SBO ? grado 1, o muerte, o retrasplante Incidencia de SBO (hasta finalizar el estudio): ?Número y severidad de los episodios de SBO desde la inclusión hasta finalizar el estudio 12011.203 (seguimiento de seguridad) Pruebas de la función pulmonar (PFP) (en cada visita al centro): ?Volumen espiratorio forzado en un segundo (VEF1). ?Flujo mesoespiratorio forzado (FEF25-75) |
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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 | Yes |
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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | 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 | 4 |
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 |
Austria |
Belgium |
Canada |
Denmark |
France |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 36 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 36 |
E.8.9.2 | In all countries concerned by the trial days | 0 |