E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bronchiolitis Obliterans Syndrome in Patients post Single or post Double Lung Transplantation |
Síndrome de bronquiolitis obliterante en pacientes tras un trasplante pulmonar simple o doble |
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E.1.1.1 | Medical condition in easily understood language |
Bronchiolitis Obliterans Syndrome in Patients after Single or post Double Lung Transplantation |
Síndrome de bronquiolitis obliterante en pacientes tras un trasplante pulmonar simple o doble |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049202 |
E.1.2 | Term | Bronchiolitis obliterans |
E.1.2 | System Organ Class | 100000004855 |
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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 assess the long-term effectiveness and safety of L-CsA plus SoC in the treatment of BOS in single and double lung transplant recipients |
Evaluar la eficacia y la seguridad a largo plazo de L CsA más el tratamiento de referencia en el tratamiento del SBO en receptores de trasplante pulmonar simple y de trasplante pulmonar doble. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients who have completed all visits through the End of Treatment Visit in either BOSTON-1 or BOSTON-2, did not withdraw informed consent, and did not prematurely terminate study drug administration. 2. Patients should be on a three-drug maintenance regimen of immunosuppressive agents including tacrolimus or another CNI, a second agent such as but not limited to MMF or azathioprine, and a systemic corticosteroid such as prednisone. 3. Patients capable of understanding the purposes and risks of the clinical trial, who have given written informed consent and agree to comply with the clinical trial requirements/visit schedules, and who are capable of aerosol inhalation. 4. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to Visit 1 and must agree to use one of the methods of contraception listed in Appendix II of the protocol through their End of Study Visit. |
1. Pacientes que han completado todas las visitas hasta la visita final de tratamiento en el ensayo BOSTON-1 o BOSTON-2, no retiraron el consentimiento informado y no interrumpieron prematuramente la administración del medicamento del estudio. 2. Los pacientes deben llevar recibiendo un esquema de mantenimiento con tres inmunosupresores que incluyen tacrolimus u otro inhibidor de la calcineurina (CNI), un segundo medicamento como MMF o azatioprina, entre otros, y un corticoesteroide sistémico como prednisona. 3. Pacientes capaces de entender los propósitos y los riesgos del ensayo clínico, que han otorgado el consentimiento informado por escrito y aceptan cumplir los requisitos/calendario de visitas del ensayo clínico y que son capaces de inhalar el aerosol. 4. Las mujeres en edad fértil deben tener una prueba de embarazo en suero negativa en los 7 días anteriores a la visita 1 y deben aceptar utilizar uno de los métodos anticonceptivos enumerados en el Apéndice II del protocolo hasta la visita final del estudio. |
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E.4 | Principal exclusion criteria |
1. Known hypersensitivity to L-CsA or to cyclosporine A. 2. Patients who experienced an AE related to study drug that led to permanent study drug discontinuation in BOSTON-1 or BOSTON-2. 3. Patients who developed a new malignancy while participating in BOSTON-1 or BOSTON-2, including post-transplant lymphoproliferative disorder, with the exception of treated, localized basal and squamous cell carcinomas. 4. Pregnant women or women who are unwilling to use appropriate birth control to avoid pregnancy through their End of Study Visit. 5. Women who are currently breastfeeding. 6. Receipt of an investigational drug, other than L-CsA, as part of a clinical trial within 4 weeks prior to Visit 1. This is defined as any treatment that is implemented under an Investigational New Drug (IND) or compassionate use. 7. Patients who are currently participating in an interventional clinical trial, other than BOSTON-1 or BOSTON-2. 8. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures. 9. Any co-existing medical condition that in the Investigator’s judgment will substantially increase the risk associated with the patient’s participation in the clinical trial. |
1. Hipersensibilidad conocida a L-CsA o a la ciclosporina A. 2. Pacientes que presentaron un AA relacionado con el medicamento del estudio que dio lugar a la suspensión permanente del medicamento del estudio en BOSTON-1 o BOSTON-2. 3. Pacientes con neoplasias malignas nuevas que aparecieron mientras participaban en BOSTON-1 o en BOSTON-2, incluido el trastorno linfoproliferativo postrasplante, con la excepción de los carcinomas de células escamosas y basales localizados y tratados. 4. Mujeres embarazadas o mujeres que no quieren utilizar un anticonceptivo adecuado para evitar el embarazo hasta la visita final del estudio. 5. Mujeres que están actualmente en periodo de lactancia materna. 6. Pacientes que han recibido un medicamento en investigación, que no es L-CsA, como parte de un ensayo clínico en las 4 semanas anteriores a la visita 1. Esto se define como cualquier tratamiento que se implemente con la denominación de producto en fase de investigación clínica (PEI) o de uso compasivo. 7. Pacientes que están participando actualmente en un ensayo clínico intervencional, que no sea BOSTON-1 o BOSTON-2. 8. Pacientes con trastornos psiquiátricos o alteraciones mentales que les impiden entender el proceso para otorgar el consentimiento informado y/o completar los procedimientos necesarios. 9. Cualquier afección médica coexistente que, en opinión del investigador, aumenta sustancialmente el riesgo asociado a la participación del paciente en el ensayo clínico. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change in forced expiratory volume in 1 second (FEV1) (mL) from baseline to week 24 |
Cambio medio en el volumen espiratorio forzado en 1 segundo (VEF1) (ml) desde el valor basal hasta la semana 24 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Mean change in FEV1 (mL) from baseline to Week 48 • Mean change in FEV1 (mL) from baseline to End of Study • Mean change in FEV1/forced vital capacity (FVC) from baseline to Week 24 • Mean change in FEV1/FVC from baseline to Week 48 • Time to progression of BOS, defined as the earliest of the following: o Absolute decrease from baseline in FEV1 >/= 10% or >/=200 mL and absolute decrease in FEV1/FVC of > 5%, OR o Change in BOS severity (according to criteria in Verleden 2019), OR o Re-transplantation, OR o Death from respiratory failure |
• Cambio medio en VEF1 (ml) desde el valor basal hasta la semana 48 • Cambio medio en VEF1 (ml) desde el valor basal hasta el final del estudio • Cambio medio en VEF1/capacidad vital forzada (CVF) desde el valor basal hasta la semana 24 • Cambio medio en VEF1/CVF desde el valor basal hasta la semana 48 • Tiempo hasta la progresión del SBO, definida como lo que suceda primero entre los siguientes: o Disminución absoluta desde el valor basal en VEF1 10 % o 200 ml y disminución absoluta en VEF1/CVF >5 %, O o Cambio en la gravedad del SBO (de acuerdo con los criterios en Verleden 2019), O o Retrasplante, O o Muerte por fallo respiratorio |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
• week 48 • end of study • week 24 • week 48 • Time to progression |
• semana 48 • fin del estudio • semana 24 • semana 48 • Tiempo hasta la progresión |
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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 | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Ensayo de ampliación abierto |
Open label extension 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 | No |
E.8.2.3 | Other | No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
France |
Germany |
Israel |
Spain |
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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LVLS |
UVUP (Ultima Visita Ultimo Paciente) |
|
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 | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 2 |