E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Inflammatory stenosis in patient with Crohn's disease. |
Estenosis inflamatoria en pacientes con enfermedad de Crohn. |
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E.1.1.1 | Medical condition in easily understood language |
Intestinal inflamatory constriction in patients with Crohn's disease. |
Estrechamiento por inflamación intestinal en pacientes con enfermedad de Crohn. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the feasibility and safety of laparoscopic administration of allogeneic adMSCs for the treatment of patients with inflammatory intestinal stenosis associated with Crohn's disease. |
Evaluar la factibilidad y seguridad de la administración de adMSCs alogénicas por vía laparoscópica para el tratamiento de pacientes con estenosis inflamatorias intestinales asociadas a la Enfermedad de Crohn. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the preliminary efficacy of the treatment. To evaluate changes in the quality of life of treated patients using the IBDQ32 questionnaire. |
Evaluar la eficacia preliminar del tratamiento. Evaluar los cambios en la calidad de vida de los pacientes tratados mediante el cuestionario de IBDQ32. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients who agree to participate and agree to give their written consent. 2. 2. Patients over 18 years of age and under 75 years of age. 3. With Crohn's disease diagnosed at least 6 months earlier who meet clinical, endoscopic, histological and/or radiological criteria. 4. Presence of a single inflammatory stenotic lesion in the small bowel or ileocolic area with a maximum length of 5 cm, demonstrated by enteroresonance, producing episodes of intestinal occlusion/subocclusion. Other inflammatory lesions are acceptable, but only one should be identified as the obvious cause of the occlusion/subocclusion. 5. Patients treated with at least one biologic drug and with inadequate response to maintenance doses and prior to intensification (either dose, interval or change/addition of another drug): a. anti-TNF (for at least 14 weeks, which includes induction and/or maintenance doses): Infliximab, Adalimumab, Certolizumab. b. Anti-integrin(at least for 14 weeks, which includes induction and/or maintenance doses): Vedolizumab c. Anti-IL-12/23(at least for 16 weeks, which includes induction and/or maintenance doses): Ustekinumab 6. Women of childbearing age must have a negative pregnancy test at screening and agree to use effective contraceptive measures for the duration of study participation*. |
1. Pacientes que aceptan participar y estén de acuerdo con dar su consentimiento por escrito. 2. Pacientes mayores de 18 años y menores de 75 años 3. Con enfermedad de Crohn diagnosticada al menos 6 meses antes que cumplan criterios clínicos, endoscópicos, histológicos y/o radiológicos. 4. Presencia de lesión estenótica inflamatoria única en el intestino delgado o área ileocolica con una longitud máxima de 5 cm, demostrada mediante enteroresonancia, que produzca episodios de oclusión/suboclusión intestinal. Se admite que existan otras lesiones inflamatorias, pero solo una debe ser identificada como causa evidente de la oclusión/suboclusión. 5. Pacientes tratados al menos con un fármaco biológico y con inadecuada respuesta a dosis de mantenimiento y antes de la intensificación (ya sea de dosis, de intervalo o cambio/adición de otro medicamento): a. antiTNF (al menos durante 14 semanas, que incluye dosis de inducción y/o mantenimiento): Infliximab, Adalimumab, Certolizumab b. Anti-integrina(al menos durante 14 semanas, que incluye dosis de inducción y/o mantenimiento): Vedolizumab c. Anti-IL-12/23(al menos durante 16 semanas, que incluye dosis de inducción y/o mantenimiento): Ustekinumab 6. Las mujeres en edad fértil deben presentar un test de embarazo negativo en el período de selección y comprometerse a usar medidas anticonceptivas eficaces durante el tiempo que dure su participación en el estudio* |
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E.4 | Principal exclusion criteria |
1. Intra-abdominal abscesses larger than 3 cm not drained (surgically, by interventional radiology) or not treated with antibiotics. Patients may be included once the abscess has been drained (without the need to wait) or if they have received antibiotic treatment, once improvement has been confirmed with imaging tests. 2. Severe intestinal obstruction that requires urgent surgery 3. Active outbreak of Crohn's disease requiring medical treatment, defined as abdominal pain, fever, bloody diarrhea and CRP greater than 10. The patient may be included once the condition has resolved, when the patient is on maintenance medication. 4. History of previous invasive neoplasia in the last 5 years. Patients with completely resected basal cell carcinoma of the skin may be included 5. History in the last 6 months of severe, progressive or uncontrolled hepatic, hematological, gastrointestinal, renal, endocrine, pulmonary, cardiac, neurological or psychiatric disease. 6. Patients with primary sclerosing cholangitis. 7. Patients with known congenital or acquired immunodeficiency, including HIV. 8. Known allergy or hypersensitivity to penicillin or aminoglycosides; DMEN (dulbecco modified eagle's medium), bovine serum, local anesthetic or gadolinium. 9. Contraindication to perform MRI (pacemaker, hip replacement or severe claustrophobia) or receive contrast with gadolinium. 10. Patients unwilling or unable to comply with study procedures. 11. Patients who are receiving, or have received any investigational medication in the 3 months prior to the screening period. 12. Major surgery or severe trauma in the previous 6 months. 13. Pregnant or lactating women. 14. Patients who have contraindications for general anesthesia, locoregional (depending on the type of anesthesia required) or laparoscopy1. Intra-abdominal abscesses larger than 3 cm not drained (surgically, by interventional radiology) or not treated with antibiotics. Patients may be included once the abscess has been drained (without the need to wait) or if they have received antibiotic treatment, once improvement has been confirmed with imaging tests. 2. Severe intestinal obstruction that requires urgent surgery 3. Active outbreak of Crohn's disease requiring medical treatment, defined as abdominal pain, fever, bloody diarrhea and CRP greater than 10. The patient may be included once the condition has resolved, when the patient is on maintenance medication. 4. History of previous invasive neoplasia in the last 5 years. Patients with completely resected basal cell carcinoma of the skin may be included 5. History in the last 6 months of severe, progressive or uncontrolled hepatic, hematological, gastrointestinal, renal, endocrine, pulmonary, cardiac, neurological or psychiatric disease. 6. Patients with primary sclerosing cholangitis. 7. Patients with known congenital or acquired immunodeficiency, including HIV. 8. Known allergy or hypersensitivity to penicillin or aminoglycosides; DMEN (dulbecco modified eagle's medium), bovine serum, local anesthetic or gadolinium. 9. Contraindication to perform MRI (pacemaker, hip replacement or severe claustrophobia) or receive contrast with gadolinium. 10. Patients unwilling or unable to comply with study procedures. 11. Patients who are receiving, or have received any investigational medication in the 3 months prior to the screening period. 12. Major surgery or severe trauma in the previous 6 months. 13. Pregnant or lactating women. 14. Patients who have contraindications for general anesthesia, locoregional (depending on the type of anesthesia required) or laparoscopy |
1. Abscesos intraabdominales mayores de 3 cm no drenados (quirúrgicamente, por radiología intervencionista) o no tratados con antibióticos. Se podrán incluir pacientes una vez drenado el absceso (sin necesidad de esperar) o si ha recibido tratamiento antibiótico, una vez confirmada la mejoría con prueba de imagen. 2. Cuadro de obstrucción intestinal severa que requiera cirugía urgente 3. Brote activo por enfermedad de Crohn que requiera tratamiento médico, definido como dolor abdominal, fiebre, diarrea sanguinolenta y PCR mayor de 10. Se podrá incluir al paciente una vez resuelto el cuadro, cuando el paciente se encuentre con medicación de mantenimiento. 4. Historia de neoplasia invasiva previa en los últimos 5 años. Pacientes con carcinoma de células basal de la piel completamente resecado pueden ser incluidos 5. Historia en los últimos 6 meses de enfermedad severa, progresiva o incontrolada hepática, hematológica, gastrointestinal, renal, endocrina, pulmonar, cardiaca, neurológica o psiquiátrica. 6. Pacientes con colangitis esclerosante primaria. 7. Pacientes con inmunodeficiencia congénita o adquirida conocidas, incluido VIH. 8. Alergia o hipersensibilidad conocida a penicilina o aminoglucósidos; DMEN (dulbecco modified eagle´s medium), serum bovino, anestésico local o gadolinium. 9. Contraindicación para realizar RMN (marcapasos, prótesis de cadera o claustrofobia severa) o recibir contraste con gadolinio. 10. Pacientes que no quieran o no puedan cumplir con los procedimientos del estudio. 11. Pacientes que estén recibiendo, o hayan recibido cualquier medicamento en investigación en los 3 meses previos al periodo de selección. 12. Cirugía mayor o trauma severo en los 6 meses previos. 13. Mujeres embarazadas o en periodo de lactancia. 14. Pacientes que tengan contraindicación para anestesia general, locorregional (en función del tipo de anestesia que se precise) o realización de laparoscopia |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Complications during anesthesia: (depending on the type of anesthesia)
- Complications derived from the treatment administration procedure o Associated with laparoscopy o Associated with injection into perilesional fat o Associated with the investigational drug |
- Complicaciones durante la anestesia: (en función del tipo de anestesia)
- Complicaciones derivadas del procedimiento de administración del tratamiento o Asociadas a la laparoscopia o Asociadas a la inyección en la grasa perilesional o Asociadas al medicamento en investigación |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
VISIT 0 TO VISIT 6 |
VISITA 0 A VISITA 6 |
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E.5.2 | Secondary end point(s) |
- To evaluate the change in the length of the stenosis with respect to the baseline in the enteroMRI - To assess the change in the CDAI questionnaire score from baseline at 6, 12, 18, 24, 36 and 52 weeks - To assess the change in score from baseline on the IBDQ32 questionnaire at 24 and 52 weeks of treatment - To describe the number of patients with an obstructive episode who required resection surgery during the study period. |
a. Evaluar el cambio en la longitud de la estenosis respecto del basal en la enteroRMN b. Evaluar el cambio en la puntuación del cuestionario CDAI respecto del basal a las 6, 12, 18, 24, 36 y 52 semanas c. Evaluar el cambio en la puntuación respecto del basal en el cuestionario de IBDQ32 a las 24 y 52 semanas del tratamiento d. Describir el número de pacientes con episodio obstructivo que hayan requerido una cirugía de resección durante el periodo del estudio. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
6, 12, 18, 24, 36 and 52 weeks |
6, 12, 18, 24, 36 y 52 semanas |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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LVLS |
Ultima visita ultimo paciente |
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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 | |
E.8.9.1 | In the Member State concerned months | 36 |
E.8.9.1 | In the Member State concerned days | |