E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Crohn's Disease |
Enfermedad de Crohn |
|
E.1.1.1 | Medical condition in easily understood language |
Crohn's Disease a form of inflammatory bowel disease. |
Enfermedad de Crohn, una forma de enfermedad inflamatoria intestinal. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
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 | 10011401 |
E.1.2 | Term | Crohn's disease |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 dose-response relationship of 2 doses of etrasimod versus placebo as induction therapy in subjects with moderately to severely active Crohn’s disease (CD). To select an oral etrasimod dose, based on efficacy and safety, for continued development. |
• Evaluar la relación dosis-respuesta de 2 dosis de etrasimod versus placebo como terapia de inducción en sujetos con enfermedad de Crohn (EC) de moderada a severamente activa. Seleccionar una dosis oral de etrasimod, basada en la eficacia y la seguridad, para un desarrollo continuo. |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the long-term safety, tolerability, and efficacy of etrasimod in subjects with moderately to severely active Crohn’s disease (CD). |
• Evaluar la seguridad, la tolerabilidad y la eficacia a largo plazo del etrasimod en sujetos con enfermedad de Crohn (EC) de moderada a severamente activa. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men or women 18 to 80 years of age, 2. Ability to provide written informed consent and to be compliant with the schedule of protocol assessments 3. Diagnosed with CD ≥ 3 months 4.Have moderately to severely active CD at Screening 5.Demonstrated inadequate response, loss of response to, or intolerance to ≥ 1 of the following therapies for the treatment of CD: a.Oral corticosteroids (eg, prednisone or its equivalent, budesonide) b.Immunosuppressants (eg, azathioprine [AZA], 6 mercaptopurine [6 MP], or methotrexate [MTX]) c.Tumor necrosis factor alpha (TNFα) antagonists (eg, infliximab, adalimumab, certolizumab pegol, or biosimilars) d.Integrin receptor antagonist (eg, vedolizumab) e.Interleukin 12/ 23 antagonist (eg, ustekinumab) 6.Females of childbearing potential must be nonpregnant 7.Females of childbearing potential and males must use contraception |
1. Hombres o mujeres de 18 a 80 años de edad, 2. Capacidad para proporcionar un consentimiento informado por escrito y cumplir con el cronograma de evaluaciones de protocolo 3. Diagnosticado con EC ≥ 3 meses 4. Tener EC moderada a severamente activa en la detección 5. Respuesta inadecuada demostrada, pérdida de respuesta o intolerancia a ≥ 1 de las siguientes terapias para el tratamiento de la EC: a.Corticosteroides orales (p. ej., prednisona o su equivalente, budesonida) B. Inmunosupresores (p. ej., azatioprina [AZA], 6 mercaptopurina [6 MP] o metotrexato [MTX]) c. antagonistas del factor de necrosis tumoral alfa (TNFα) (p. ej., infliximab, adalimumab, certolizumab pegol o biosimilares) d. Antagonista del receptor de integridad (p. ej., vedolizumab) e.Interleukin 12/23 antagonista (por ejemplo, ustekinumab) 6. Las mujeres en edad fértil no deben estar embarazadas. 7. Las mujeres en edad fértil y los hombres deben usar anticonceptivos. |
|
E.4 | Principal exclusion criteria |
- History of inadequate response (ie, primary non response) to agents from ≥ 2 classes of biologics marketed for the treatment of CD (ie, TNFα antagonists, interleukin 12/ 23 antagonist, and integrin receptor antagonist). - Have ulcerative colitis, indeterminate colitis, microscopic colitis, ischemic colitis, radiation colitis, diverticular disease associated colitis, toxic megacolon, or active infectious colitis or test positive for Clostridium difficile toxin at Screening. - Have functional or post operative short bowel syndrome or any associated complications that may require surgery or interfere with efficacy assessments - Had surgical treatment for intra abdominal abscesses ≤ 8 weeks prior to randomization or surgical treatment for perianal abscesses ≤ 4 weeks prior to randomization. - Had intestinal resection ≤ 24 weeks prior to randomization or other intra abdominal surgeries ≤ 12 weeks prior to randomization. - Have an ileostomy or a colostomy. - Have a serious infection requiring IV antibiotics/medication(s) ≤ 4 weeks prior to randomization. - Have primary or secondary immunodeficiency syndromes, opportunistic infection, or infection with HIV, HBV, HCV or tuberculosis (active or latent):. - Have a clinically relevant cardiovascular condition or receiving treatments that may effect cardiovascular function - Have active retinopathy or macular oedema. - Have forced expiratory volume at 1 second or forced vital capacity < 70% of predicted values at Screening. - Lactating female who is breastfeeding. - Any acute illnesses or medical conditions including cognitive impairment and alcohol/drug abuse/dependence, or signs/symptoms suspicious for a serious disease that, in the Investigator's opinion, could put the subject at increased risk for safety event(s) or interfere with protocol-specified procedures or adherence with study treatment. |
Historial de respuesta inadecuada (es decir, falta de respuesta primaria) a agentes de ≥ 2 clases de productos biológicos comercializados para el tratamiento de EC (es decir, antagonistas de TNFα, antagonista de interleucina 12/23 y antagonista del receptor de integrina). - Tener colitis ulcerosa, colitis indeterminada, colitis microscópica, colitis isquémica, colitis por radiación, colitis asociada a enfermedad diverticular, megacolon tóxico o colitis infecciosa activa o prueba positiva para la toxina de Clostridium difficile en el cribado. - Tener síndrome funcional o postoperatorio de intestino corto o cualquier complicación asociada que pueda requerir cirugía o interferir con las evaluaciones de eficacia - Haber tenido tratamiento quirúrgico para abscesos intraabdominales ≤ 8 semanas antes de la aleatorización o tratamiento quirúrgico para abscesos perianales ≤ 4 semanas antes de la aleatorización. - Haber tenido resección intestinal ≤ 24 semanas antes de la aleatorización u otras cirugías intraabdominales ≤ 12 semanas antes de la aleatorización. - Tener una ileostomía o una colostomía. - Tener una infección grave que requiere antibióticos / medicamentos por vía intravenosa ≤ 4 semanas antes de la aleatorización. - Tener síndromes de inmunodeficiencia primaria o secundaria, infección oportunista o infección por VIH, VHB, VHC o tuberculosis (activa o latente): - Tener una enfermedad cardiovascular clínicamente relevante o recibir tratamientos que puedan afectar la función cardiovascular - Tener retinopatía activa o edema macular. - Tener un volumen espiratorio forzado a 1 segundo o una capacidad vital forzada <70% de los valores pronosticados en la detección. - Ser mujer lactante que está amamantando. - Cualquier enfermedad aguda o afección médica que incluya deterioro cognitivo y abuso / dependencia de alcohol / drogas, o signos / síntomas sospechosos de una enfermedad grave que, en opinión del investigador, podría poner al sujeto en mayor riesgo de eventos de seguridad o interferir con procedimientos especificados por protocolo o adherencia al tratamiento del estudio. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects who achieve endoscopic response at Week 14 |
Proporción de sujetos que logran respuesta endoscópica en la semana 14 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Proportion of subjects who achieve clinical remission APSF at Week 14 • Proportion of subjects who achieve CDAI < 150 by visit up to Week 14 • Proportion of subjects who achieve clinical response CDAI by visit up to Week 14 • Proportion of subjects who achieve clinical response APSF by visit up to Week 14 • Proportion of subjects who achieve clinical response CDAI-70 by visit up to Week 14 • Proportion of subjects who achieve clinical response APSF-30 by visit up to Week 14 • Change from baseline in CDAI score by visit up to Week 14 • Change from baseline in SES-CD at Week 14 • Proportion of subjects with clinical response by PRO2 at Week 14 • Proportion of subjects with endoscopic response and clinical remission by PRO2 at Week 14 • Change and percentage change from baseline in absolute lymphocyte count by visit up to Week 14 • Change and percentage change from baseline in FCP concentration at Weeks 2, 4, 6, 10, and 14 • Change and percentage change from baseline in CRP concentration at Weeks 2, 4, 6, 10, and 14 • Proportion of subjects who achieve endoscopic remission at Week 14 Extension Period: endpoints for the induction period will be assessed at scheduled visits up to Week 66. |
• Proporción de sujetos que logran remisión clínica APSF en la semana 14 • Proporción de sujetos que alcanzan CDAI <150 por visita hasta la semana 14 • Proporción de sujetos que logran respuesta clínica CDAI por visita hasta la semana 14 • Proporción de sujetos que logran respuesta clínica APSF por visita hasta la semana 14 • Proporción de sujetos que logran respuesta clínica CDAI-70 por visita hasta la semana 14 • Proporción de sujetos que logran respuesta clínica APSF-30 por visita hasta la semana 14 • Cambio desde la línea de base en el puntaje CDAI por visita hasta la semana 14 • Cambio desde la línea de base en SES-CD en la semana 14 • Proporción de sujetos con respuesta clínica por PRO2 en la semana 14 • Proporción de sujetos con respuesta endoscópica y remisión clínica por PRO2 en la semana 14 • Cambio y porcentaje de cambio desde el inicio en el recuento absoluto de linfocitos por visita hasta la semana 14 • Cambio y porcentaje de cambio desde el inicio en la concentración de FCP en las semanas 2, 4, 6, 10 y 14 • Cambio y cambio porcentual desde el inicio en la concentración de PCR en las semanas 2, 4, 6, 10 y 14 • Proporción de sujetos que alcanzan la remisión endoscópica en la semana 14 Periodo de extensión: Los puntos finales para el período de inducción se evaluarán en las visitas programadas hasta la semana 66. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
by visit up to week 66 |
por visita, hasta la semana 66 |
|
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 | 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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
dose finding |
Encontrar la dosis |
|
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 | 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 | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 214 |
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 |
Argentina |
Australia |
Belarus |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
China |
Colombia |
Croatia |
Czech Republic |
Denmark |
Egypt |
France |
Georgia |
Germany |
Hungary |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
Latvia |
Lebanon |
Lithuania |
Mexico |
Moldova, Republic of |
Norway |
Peru |
Poland |
Portugal |
Puerto Rico |
Romania |
Russian Federation |
Serbia |
Slovakia |
Slovenia |
South Africa |
Spain |
Sweden |
Switzerland |
Taiwan |
Thailand |
Turkey |
Ukraine |
United Kingdom |
United States |
|
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
|
LVLS |
Última visita del último paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 29 |