| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Ulcerative Colitis |
| Colitis Ulcerosa |
|
| E.1.1.1 | Medical condition in easily understood language |
| Ulcerative Colitis is a type of inflammatory bowel disease that causes the lining of the large intestine (colon) to become inflamed (irritated and swollen) which may cause ulcers and bleeding. |
| La colitis ulcerosa es una enfermedad inflamatoria intestinal que provoca inflamación en el revestimiento del intestino grueso con irritación e hinchazón, que puede causar úlceras y hemorragias. |
|
| 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 | 20.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10045365 |
| E.1.2 | Term | Ulcerative colitis |
| E.1.2 | System Organ Class | 100000004856 |
|
| 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 assess the safety of long-term treatment with brazikumab in UC participants who previously completed or discontinued participation due to lack of efficacy after Week 10 in the lead-in Study D5272C00001 (Legacy #3151-201-008) |
| Evaluar la seguridad del tratamiento a largo plazo con brazikumab en pacientes con CU que completaron o interrumpieron su participación debido a la falta de eficacia después de la semana 10 en el ensayo D5272C00001 |
|
| E.2.2 | Secondary objectives of the trial |
| Not applicable |
| No aplicable |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Male or female participants who:
1. successfully completed or discontinued participation due to lack of efficacy after Week 10 in the lead-in Study D5272C00001.
AND
Meets 1 of the following criteria for successful completion or early termination from Study D5272C00001:
(a) Participant completed Study D5272C00001, received scheduled study interventions, completed scheduled visits, and completed Week 54 assessments.
(b) Participant discontinued participation due to lack of efficacy after Week 10 in Study D5272C00001, received scheduled study interventions, and completed Early Termination Visit assessments.
2. No known history of active TB or latent TB without completion of appropriate intervention.
3. Male participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period. Nonsterilized men who are sexually active with a female partner of childbearing potential should use condom during treatment and for 18 weeks after the last dose of study intervention
4. Female participants of childbearing potential must have a negative urine pregnancy test prior to administration of study intervention and must agree to use a highly effective method of birth control (confirmed by the investigator) from randomization throughout the study duration and for at least 18 weeks after last dose of study intervention
5. Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal.
6. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
7. Written informed consent from the participant has been obtained prior to any study related procedures.
8. Written documentation has been obtained in accordance with the relevant country and local privacy requirements, where applicable (eg, Written Authorization for Use and Release of Health and Research Study Information [US sites] and written Data Protection consent [EU sites]).
9. Demonstration of adequate compliance with the study procedures in Study D5272C00001, in the opinion of the investigator and/or sponsor.
10. Willingness and ability to attend all study visits, comply with the study procedures, and be able to complete the study period.
11. Participant must be 18 to 80 years of age inclusive, at the time of signing the ICF.
Complete inclusion criteria are in the study protocol |
Pacientes adultos que:
1. Finalizaron satisfactoriamente o interrumpieron su participación por falta de eficacia tras la semana 10 en el ensayo D5272C00001.
Y
Cumplen 1 de estos criterios:
(a) El paciente completó el ensayo D5272C00001, recibió el tratamiento en investigación y completó todas las visitas programadas, incluidas las evaluaciones de la semana 54.
(b) El paciente interrumpió su participación por falta de eficacia tras la semana 10 en el ensayo D5272C00001, recibió el tratamiento en investigación y completó la visita de retirada temprana.
2. Sin antecedentes de TB activa latente.
3. Los hombres sexualmente activos con pareja en edad fértil deben utilizar preservativo durante el ensayo y hasta 18 semanas después de la última dosis del tratamiento del ensayo.
4. Las mujeres en edad fértil con una prueba de embarazo en orina negativa antes de la administración del tratamiento en investigación, deben utilizar un método anticonceptivo altamente eficaz desde la aleatorización y hasta al menos 18 semanas después de la última dosis de tratamiento en investigación.
5. Mujeres , con esterilización permanente (histerectomía, ovariectomía bilateral o salpingectomía bilateral) o posmenopáusicas.
6. Capaz de otorgar y firmar un consentimiento informado.
7. Se ha obtenido el consentimiento informado por escrito del paciente antes de realizar cualquier procedimiento del ensayo.
8. Se ha obtenido por escrito el consentimiento para la protección de datos personales.
9. Capacidad para el cumplimiento adecuado de los procedimientos del ensayo D5272C00001 en opinión del investigador y/o el promotor.
10. Voluntad y capacidad para asistir a todas las visitas del estudio, y cumplir con los procedimientos.
11. Paciente entre 18 y 80 años, en el momento de firmar el consentimiento informado.
Los criterios de inclusión completos se describen en el protocolo del ensayo. |
|
| E.4 | Principal exclusion criteria |
1. Any participant with an unresolved AE from the lead-in study that, in the investigator’s opinion, would limit the participant’s ability to participate in or complete this study. Any unresolved AE related to an infection will require further discussion with the study medical monitor prior to enrollment.
2. Current diagnosis of fulminant colitis, CD or indeterminate colitis, presence of a fistula consistent with CD, primary sclerosing cholangitis, celiac disease, or toxic megacolon. Bile acid malabsorption and other conditions that may potentially confound assessments must be treated prior to baseline.
3. Organ or cell-based transplantation with the exception of corneal transplant.
4. Any other condition or finding that, in the investigator’s or sponsor’s opinion, would either confound proper interpretation of the study or expose a participant to unacceptable risk.
5. The following are exclusionary with regards to malignancy:
a) Evidence of intestinal epithelial dysplasia on endoscopy, and this is confirmed on biopsy, the participant.
b) Any diagnosis of malignancy that requires discontinuation of study intervention from lead-in study.
c) Any new diagnosis of malignancy after completion of the lead-in study.
d) Carcinoma in situ of the cervix, with apparent successful curative therapy within 12 months prior to Week 0.
6. Participant meets criteria for discontinuation of study intervention during prior lead-in study.
7. Chronic hepatitis B or C infection
8. Known history of primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection, including HIV infection.
9. Prolonged QTcF interval or conditions leading to additional risk for QT prolongation. Participants with electrolyte abnormalities such as hypokalemia and hypomagnesemia that would increase the risk of QT prolongation are to be corrected prior to enrollment.
10. Clinically significant kidney disease including but not limited to:
(a) Chronic kidney disease with an estimated glomerular filtration rate of less than 30 ml/min calculated by Modification of Diet in Renal Disease equation.
11. Participant requires additional immunosuppressive therapy (aside from permitted concomitant medication in the protocol), biological treatment or prohibited treatment
12. Participant received a prohibited medication during participation in the D5272C00001 study.
13. Participant received a Bacille Calmette-Guérin vaccination within 12 months of Week 0 or any other live vaccine < 4 weeks prior to Week 0, or is planning to receive any such vaccine over the course of the study.
14. Participant has received an investigational product after discontinuation from Study D5272C00001 and prior to enrolling in this study or participant is planning to receive an investigational drug (other than study intervention) or investigational device at any time during Study D5272C00002.
15. Participant who discontinued participation due to lack of efficacy after Week 10 in Study D5272C00001 and did not receive all 3 IV infusions of study interventions scheduled for Week 0 (Day 1), Week 2 (Day 15), and Week 6 (Day 43), and SC at Week 10 (Day 71) in accordance with the protocol for Study D5272C00001.
16. Participant who discontinued due to lack of efficacy after Week 10 in Study D5272C00001 but currently demonstrates clinical response and/or meets endoscopic Mayo Score of 0 or 1 prior to Week 54 in Study D5272C00001:
Clinical Response defined as: Reduction in mMS ≥ 2 points from baseline AND ≥ 30% from baseline, AND a decrease in the rectal bleeding score ≥ 1 point from baseline or a score of 0 or 1, in Study D5272C00001.
Note: Participants are encouraged to remain in the lead-in Study D5272C00001 if the participant is demonstrating evidence of clinical response. Participants should not early terminate that study due to lack of efficacy if this exclusion is met.
17. Abnormal laboratory results at screening as described in the protocol.
18. Females who are pregnant, breast feeding, or planning a pregnancy during the study OR females who are of childbearing potential and do not agree to use contraception.
19. Participant is directly or indirectly involved in the planning and/or conduct and administration of this study as study staff member, or employee of the sponsor, or the participant is a first-degree family member, significant other, or relative residing with one of the above persons involved directly or indirectly in the study; or the participant is enrolled in this study at another clinical study site.
20. Judgment that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
21. Previous enrollment in the present study.
Complete exclusion criteria are in the study protocol |
1. Paciente con un AA no resuelto del ensayo D5272C00001 que, en opinión del investigador, limitaría su capacidad para participar en elensayo. Un AA no resuelto relacionado con una infección requerirá consulta con el monitor médico del ensayo antes de la inclusión.
2. Diagnóstico actual de colitis fulminante, EC o colitis indeterminada, presencia de fístula compatible con EC, colangitis esclerosante primaria, enfermedad celíaca o megacolon tóxico, malabsorción de ácidos biliares y otras afecciones que puedan confundir las evaluaciones deben tratarse antes de la inclusión.
3. Trasplante de órganos o células, excepto trasplantes de córnea.
4. Cualquier otra afección que, en opinión del investigador o promotor, pueda confundir la interpretación del ensayo o exponer la seguridad del paciente.
5. Con respecto a neoplasias malignas son excluyentes: a) Indicios de displasia epitelial intestinal en la endoscopia confirmado por bipsia.
b) Un diagnóstico de neoplasia maligna que requiera la interrupción del tratamiento del ensayoD5272C00001.
c) Un nuevo diagnóstico de neoplasia maligna tras la finalización del ensayo D5272C00001.
d) Carcinoma in situ del cuello uterino, con tratamiento curativo satisfactorio evidente en los 12 meses anteriores a la semana 0.
6. Paciente que cumple los criterios de interrupción del tratamiento del ensayo D5272C00001.
7. Infección crónica por hepatitis B o C
8. Antecedentes conocidos de inmunodeficiencia primaria, esplenectomía o afección subyacente que predisponga al paciente a una infección, incluida VIH.
9. Intervalo QTcF prolongado o riesgo de prolongación del intervalo QT. Las anomalías electrolíticas como hipopotasemia e hipomagnesemia que aumentarían el riesgo de prolongación del intervalo QT deben corregirse antes de la inclusión.
10. Enfermedad renal clínicamente significativa que incluye:
(a) Tasa de filtración glomerular <30 ml/min calculada mediante la ecuación de modificación de la dieta en la enfermedad renal.
11. Paciente que requiere tratamiento inmunodepresor (aparte de la medicación concomitante permitida en el protocolo), tratamiento biológico o tratamiento prohibido.
12. Paciente que recibió medicación prohibida durante su participación en el ensayo D5272C00001.
13. El paciente recibió una vacuna contra el bacilo de Calmette-Guérin 12 meses antes de la semana 0 o cualquier otra vacuna viva <4 semanas antes de la semana 0, o tiene previsto recibir dicha vacuna durante el transcurso del estudio.
14. El paciente ha recibido un medicamento en investigación tras la interrupción del ensayo D5272C00001 y antes de la inclusión en este ensayo, o tiene previsto recibir tratamiento en investigación o producto sanitario en investigación durante el ensayo D5272C00002.
15. Paciente que interrumpió su participación debido a la falta de eficacia tras la semana 10 en el ensayo D5272C00001 y no recibió las 3 infusiones i.v. del tratamiento en investigación en la semana 0 (día 1), semana 2 (día 15) y semana 6 (día 43), y s.c. en la semana 10 (día 71) de acuerdo con el protocolo del ensayo D5272C00001.
16. Paciente que interrumpió el tratamiento en investigación por falta de eficacia tras la semana 10 en el ensayo D5272C00001 que muestra respuesta clínica y/o cumple subíndice endoscópico Mayo0-1 antes de la semana 54 en el ensayo D5272C00001:
La respuesta clínica se define como: Reducción de la mMS ≥2 puntos desde el inicio Y ≥30 % desde el inicio Y disminución del subíndice de hemorragia rectal ≥1 punto desde el inicio o puntuación de 0-1, en el ensayo D5272C00001. Se anima a los pacientes a permanecer en el ensayoD5272C00001 si está demostrando indicios de respuesta clínica. Los pacientes no deben retirarse prematuramente por falta de eficacia si se cumple esta exclusión.
17. Resultados analíticos anormales en la selección según se describe en el protocolo.
18. Mujeres embarazadas, en periodo de lactancia o que tienen previsto quedarse embarazadas durante el estudio O bien mujeres en edad fértil que no acepten utilizar métodos anticonceptivos.
19. El paciente participa directa o indirectamente en la planificación, realización y/o administración como personal del ensayo, miembro del promotor, o es pariente de primer grado, pareja, o familiar que reside con personas implicadas directa o indirectamente en el ensayo; o está participando en otro centro del ensayo clínico.
20. Si el investigador considera que el paciente no debería participar si es improbable que cumpla con los requisitos del ensayo.
21. Inclusión previa en el presente ensayo.
Los criterios de exclusión completos se encuentran en el protocolo del ensayo. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
- AEs
- Clinical laboratory values
- Vital signs
-Physical exams
- ECGs |
- AA
- Valores analíticos clínicos
- Constantes vitales
- Exploraciones físicas
- Electrocardiogramas |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Across the 52-week treatment period for each primary endpoints |
| A lo largo del periodo de tratamiento de 52 semanas para cada criterio de valoración principal. |
|
| E.5.2 | Secondary end point(s) |
| Not applicable |
| No aplicable |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Not applicable |
| No aplicable |
|
| 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 | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| Ensayo de extensión |
| Extension study |
|
| 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.8.2.4 | 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 80 |
| 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 |
| Canada |
| India |
| Israel |
| Japan |
| Korea, Republic of |
| Russian Federation |
| South Africa |
| Taiwan |
| Ukraine |
| United States |
| Austria |
| France |
| Germany |
| Hungary |
| Italy |
| Poland |
| Spain |
| United Kingdom |
| Czechia |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 10 |
| 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 | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 5 |
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