E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe Ulcerative Colitis. |
Colitis Ulcerosa Moderada a Severa |
|
E.1.1.1 | Medical condition in easily understood language |
In Ulcerative Colitis the lining of the colon becomes inflamed and develops tiny open sores that produce pus and mucous.This causes abdominal discomfort and frequent emptying of the colon (diarrhoea). |
En la Colitis ulcerosa los revestimientos del colon se inflaman y se crean pequeñas heridas abiertas que producen pus y mucosa. Esto causa malestar abdominal y diarrea |
|
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 | 10066678 |
E.1.2 | Term | Acute 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 |
The primary objective of the study is to evaluate the long term safety of ABX464 given at 50 mg once daily in subjects with Moderate to Severe Active Ulcerative Colitis. |
El objetivo principal del estudio es evaluar la seguridad de ABX464 con dosis de 50 mg una vez al día en pacientes con colitis ulcerosa activa de moderada a grave. |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the long term effect of ABX464 on clinical and endoscopic remission in subjects with Moderate to Severe Active Ulcerative Colitis assessed by the MCS. • To evaluate the long-term effect of ABX464 on inflammatory markers (CRP, Calprotectin and ESR) • To evaluate the long-term of ABX464 on Quality of Life (QoL) measured by the SF-36 questionnaire in subjects with Moderate to Severe Active Ulcerative Colitis. |
▪ Evaluar el efecto a largo plazo de ABX464 en la remisión endoscópica en pacientes con Colitis Ulcerosa de moderada a grave ▪ Evaluar el efecto a largo plazo de ABX464 en marcadores inflamatorios (CRP, calprotectina y ESR) ▪ Evaluar el efecto a largo plazo de ABX464 en la Calidad de vida (CdV) determinada con el cuestionario SF-36 en pacientes con Colitis Ulcerosa de moderada a grave. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A subject will be eligible for inclusion in this study only if ALL of the following criteria apply: • Subjects previously enrolled in the ABX464-101 clinical study who have completed the initial 2-month treatment phase; • Subjects able and willing to comply with study visits and procedures; • Subjects with hematological and biochemical laboratory parameters as follows at the D56 visit of the ABX464-101 study: o Hemoglobin > 9.0 g dL-1; o Absolute neutrophil count ≥ 750 mm-3; o Platelets ≥ 100,000 mm-3; o Total serum creatinine ≤ 1.3 x ULN (upper limit of normal); o Creatinine clearance > 50 mL min-1 by the Cockcroft-Gault equation within 60 days of entry; o Total serum bilirubin < 1.5 x ULN; o Alkaline phosphatase, AST (SGOT) and ALT (SGPT) < 1.5 x ULN;
-Subjects should understand, sign and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures being performed;
-Subjects should be affiliated to a social security regimen (for French sites only);
-Females and males receiving the study treatment and their partners must agree to use a highly effective contraceptive method during the study and for 3 months after end of study or early termination. Contraception should be in place at least 2 weeks prior to study participation. Women must be surgically sterile or if of childbearing potential must use a highly effective contraceptive method. Women of childbearing potential (WOCBP) will enter the study after confirmed menstrual period and a negative pregnancy test. Highly effective methods of contraception include true abstinence, intrauterine device (IUD) or hormonal contraception associated with inhibition of ovulation, intrauterine hormone releasing system (IUS), hormonal contraception (estrogen and progestogen or progestogen only) associated with inhibition of ovulation, bilateral tubal occlusion, vasectomized partner. True abstinence is defined when this is in line with the preferred and usual lifestyle of the subject. In each case of delayed menstrual period (over one month between menstruations) confirmation of absence of pregnancy is required. This recommendation also applies to WOCBP with infrequent or irregular menstrual cycle. |
Criterios de inclusión: El paciente podrá participar en este estudio solo si cumple TODOS los criterios siguientes: ▪Pacientes que hayan participado anteriormente en el ABX464-101 studio clínico y que hayan completado los 2 meses de tratamiento; ▪Los pacientes deberán tener la capacidad y la voluntad de cumplir con las visitas y procedimientos del estudio según el protocolo. ▪Los pacientes con los siguientes parámetros de laboratorio hematológicos y bioquímicos 14 días antes de la visita inicial: o Hemoglobina > 9,0 g/dl-1 o Recuento absoluto de neutrófilos ≥ 750 mm-3 o Plaquetas ≥ 100 000 mm-3 o Creatinina sérica total ≤ 1,3 x límite superior de normalidad (LSN) o Aclaramiento de creatinina > 50 ml/min-1 mediante la ecuación de Cockcroft-Gault en el plazo de 60 días después de la entrada o Bilirrubina total en suero < 1,5 x LSN o Fosfatasa alcalina, AST (SGOT) y ALT (SGPT) < 1,5 x LSN ▪Los pacientes deberán entender, firmar y fechar el formulario de consentimiento informado voluntario por escrito en la visita de selección antes de realizar ningún procedimiento específico del protocolo. ▪Los pacientes deberán estar afiliados al régimen de la seguridad social (solo para centros en Francia). ▪Las mujeres y los hombres que reciban el tratamiento del estudio y sus respectivas parejas deben aceptar el uso de un método anticonceptivo efectivo durante el estudio y 3 meses después del final del estudio o de la finalización anticipada. El uso del método anticonceptivo deberá iniciarse al menos 2 semanas antes de participar en el estudio. Las mujeres deberán estar esterilizadas quirúrgicamente o si son mujeres en edad fértil deberán aceptar el uso de métodos anticonceptivos eficaces. Las mujeres en edad fértil entrarán en el estudio después del periodo menstrual confirmado y un resultado negativo en la prueba de embarazo. Los métodos anticonceptivos eficaces son los siguientes: abstinencia sexual real, dispositivo intrauterino (DIU) o anticonceptivos hormonales (estrógeno y progesterona ó progesterona sóla) asociados a la inhibición de la ovulación, dispositivo de liberación hormonal intrauterino, oclusión tubárica bilateral o pareja vasectomizada. La abstinencia real se define cuando dicha abstinencia es acorde con el tipo de vida preferido y habitual del paciente. En caso de retraso en el periodo menstrual (más de un mes entre menstruaciones) es necesario confirmar la ausencia de embarazo. Esta recomendación también corresponde a las mujeres en edad fértil con ciclos menstruales poco frecuentes o irregulares. |
|
E.4 | Principal exclusion criteria |
Any condition, which in the opinion of the investigator, could compromise the subject's safety or the adherence to the study protocol. |
Cualquier condición, que en opinion del investigador, pueda comprometer la salud del paciente o la adherencia al protocol del estudio. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Number of incidences of treatment-emergent adverse events in ABX464 treated subjects. |
▪Número de incidencias de acontecimientos adversos que se presentan o empeoran a partir de la primera dosis del fármaco del estudio en pacientes tratados con ABX464. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoint of evaluation of this end point from day 0 to EoS. |
Tiempo de evaluacion de este punto final desde el dia 0 al EoS. |
|
E.5.2 | Secondary end point(s) |
The change from Day 0 in Total Mayo Score. . The change from Day 0 in Partial Mayo Score. .The time to UC worsening. .The change from Day 0 in fecal calprotectin, CRP levels and ESR. .The scores and changes from Day 0 in SF-36 Questionnaire scores .The number of incidences of treatment-emergent adverse serious adverse events. .The number of incidences of treatment-emergent adverse events leading to investigational product discontinuation. .The number of incidences of specific laboratory abnormalities. |
▪El cambio respecto al día 0 en la puntuación total de la escala de la Clínica Mayo. ▪El cambio respecto al día 0 en la puntuación parcial de la escala de la Clínica Mayo. ▪El tiempo hasta el empeoramiento de la colitis ulcerosa. ▪El cambio respecto al día 0 en los niveles de calprotectina fecal, CRP y ESR. ▪Las puntuaciones y los cambios respecto al día 0 en la puntuación del cuestionario SF-36. ▪El número de incidencias de acontecimientos adversos graves que se presentan o empeoran a partir de la primera dosis del fármaco del estudio. ▪El número de incidencias de acontecimientos adversos de especial interés que se presentan o empeoran a partir de la primera dosis del fármaco del estudio. ▪El número de incidencias de acontecimientos adversos que provocan la interrupción del producto en fase de investigación clínica. ▪El número de incidencias de anomalías específicas de laboratorio. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time point of evaluation for secondary endpoints are throughout the study. |
Los tiempos de evaluación para los puntos finales secundarios están presentes durante el studio. |
|
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 | 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.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 | 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
|
|
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 | 12 |
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 | 12 |
E.8.9.2 | In all countries concerned by the trial days | 0 |