E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative colitis |
Colitis Ulcerosa |
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E.1.1.1 | Medical condition in easily understood language |
A form of inflammatory bowel disease |
una forma de enfermedad inflamatoria del intestino grueso |
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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 | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
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 |
The primary objective of this study is to evaluate the efficacy of different doses of rhuMAb Beta7 compared with placebo in patients with moderate to severe UC. |
El objetivo principal de este estudio consiste en evaluar la eficacia de diferentes dosis de rhuMAb Beta7 en comparación con placebo en pacientes con CU moderada o grave. |
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E.2.2 | Secondary objectives of the trial |
? To evaluate the safety and tolerability of rhuMAb Beta7 over a treatment period of 10 weeks and a follow-up period of 18 weeks ? To characterize the pharmacokinetic (PK) and immunogenicity (antitherapeutic antibody/ATA profile) of rhuMAb Beta7 when administered SC across dose levels |
*Evaluar la seguridad y la tolerabilidad de rhuMAb Beta7 durante un período de tratamiento de 10 semanas y un período de seguimiento de 18 semanas. *Determinar la farmacocinética (FC) y la inmunogenicidad (perfil de anticuerpos contra el tratamiento [ACT]) de rhuMAb Beta7 cuando se administra por vía SC en todos los niveles de dosis. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1) ABS4986g (Colonic Biopsy Substudy): Title: A colonic biopsy substudy in association with rhuMAb BETA7 study ABS4986g to assess changes in immune cell composition in the gut mucosa of patients receiving rhuMAb BETA7 Objectives: To improve the understanding of the mechanism of action of rhuMAb Beta7 2) ABS4986g (DNA Substudy) Title: DNA repository substudy in association with rhuMAb BETA7 (PRO145223) study ABS4986g Objectives: to perform exploratory analyses to generate hypotheses identifying genes associated with treatment response, toxicity, or disease risk. |
1) ABS4986g (subestudio de biopsia de colon): Subestudio de biopsia de colon asociado al estudio ABS4986g con rhuMAb Beta7, para evaluar los cambios en la composición de las células inmunitarias de la mucosa intestinal de pacientes tratados con rhuMAb Beta7 2) ABS4986g (subestudio de ADN): Subestudio de ADN para el banco de muestras clínicas asociado al estudio ABS4986g con rhuMAb Beta7 (PRO 145223) |
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E.3 | Principal inclusion criteria |
- Able and willing to provide written informed consent - 18-75 years of age - Males and females with reproductive potential must be willing to use a highly effective method of contraception (e.g., hormonal contraceptive [oral or patch], vaginal ring, intrauterine device, physical barrier, or vasectomized partner) from study start to a minimum of 4 months (approximately 5 half lives) after the final dose of the study drug. - Diagnosis of moderate to severe UC outpatient with an MCS of >=5, including an endoscopy subscore >= 2; a rectal bleeding subscore >= 1 (see Appendix B); and disease activity a minimum of 25 cm from the anal verge |
*Capacidad y disposición para otorgar el consentimiento informado por escrito. *Edad de 18-75 años. *Los varones y las mujeres en edad fértil deben estar dispuestos a utilizar un método anticonceptivo muy eficaz (por ejemplo, anticonceptivos hormonales [orales o en parche], anillo vaginal, dispositivo intrauterino, barrera física o pareja vasectomizada) desde el comienzo del estudio hasta un mínimo de 4 meses (aproximadamente 5 semividas) después de la última dosis del fármaco del estudio. *Diagnóstico de CU moderada o grave en un paciente ambulatorio con una puntuación MCS 5, incluida una subpuntuación endoscópica 2, una subpuntuación de rectorragia 1 (véase el Apéndice B) y actividad de la enfermedad hasta un mínimo de 25 cm del margen anal. |
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E.4 | Principal exclusion criteria |
- Moderate to severe anemia (hemoglobin < 9 g/dL) - A history or evidence of colonic mucosal dysplasia - Pregnant or lactating - Lack of peripheral venous access - Inability to comply with study protocol, in the opinion of the investigator - Significant uncontrolled co-morbidity, such as neurological, cardiac, pulmonary, renal, hepatic, endocrine, or gastrointestinal (GI) disorders - History of malignancy except completely excised basal cell carcinoma or squamous cell carcinoma of the skin - Impaired renal function (serum creatinine > 1.5 x upper limit of normal [ULN]) - Impaired hepatic function in the absence of a diagnosis of primary sclerosing cholangitis (serum transaminases > 2.5 x ULN, alkaline phosphatase > 2.5 x ULN, or abnormalities in synthetic liver function tests judged by the investigator to be clinically significant). If the patient has a diagnosis of primary sclerosing cholangitis, serum transaminases > 3 x ULN, alkaline phosphatase > 3 x ULN, or abnormalities in synthetic liver function tests (total bilirubin > 1.5 x ULN) judged by the investigator to be clinically significant. - Positive tests for antibodies indicating active or prior infection with HIV or hepatitis B (HBV) or C (HCV) - History of any opportunistic infections within 12 weeks prior to initiation of study treatment - Demyelinating disease or history of PML - Any current or recent (within 4 weeks prior to initiation of study treatment) signs or symptoms of infection - Received any investigational treatment within 12 weeks prior to initiation of study treatment (or within 5 half lives of the investigational product, whichever is greater) - Previous exposure to rhuMAb Beta7 - History of severe allergic or anaphylactic reactions to chimeric, human or humanized antibodies or fusion proteins |
*Anemia moderada o grave (hemoglobina < 9 g/dl).*Antecedentes o evidencia de displasia de la mucosa del colon.*Embarazo o lactancia.*Ausencia de acceso venoso periférico. *Incapacidad de cumplir el protocolo del estudio, en opinión del investigador. *Comorbilidad importante no controlada, como trastornos neurológicos, cardíacos, pulmonares, renales, hepáticos, endocrinos o digestivos. *Antecedentes de neoplasias malignas, excepto carcinoma basocelular o espinocelular de piel completamente extirpado. *Insuficiencia renal (creatinina sérica > 1,5 veces el límite superior de la normalidad [LSN]). *Insuficiencia hepática en ausencia de un diagnóstico de colangitis esclerosante primaria (transaminasas séricas > 2,5 veces el LSN, fosfatasa alcalina > 2,5 veces el LSN o anomalías en las pruebas de función hepática que el investigador considere con importancia clínica). Si el paciente tiene un diagnóstico de colangitis esclerosante primaria (transaminasas séricas > 3 veces el LSN, fosfatasa alcalina > 3 veces el LSN o anomalías en las pruebas de función hepática (bilirrubina total > 1,5 veces el LSN) que el investigador considere con importancia clínica). *Resultados positivos de anticuerpos indicativos de infección activa o previa por el VIH o el virus de la hepatitis B (VHB) o C (VHC). *Antecedentes de cualquier infección oportunista en las 12 semanas previas al inicio del tratamiento del estudio. *Enfermedad desmielinizante o antecedentes de LMP. *Signos o síntomas actuales o recientes (en las 4 semanas previas al inicio del tratamiento del estudio) de infección. *Recepción de cualquier tratamiento en investigación en las 12 semanas previas al inicio del tratamiento del estudio (o en el plazo de 5 semividas del producto en investigación, lo que sea mayor). *Exposición previa al rhuMAb Beta7. *Antecedentes de reacciones alérgicas intensas o anafilácticas frente a proteínas de fusión o anticuerpos humanizados, humanos o quiméricos. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients in clinical remission at Week 10. |
Proporción de pacientes en remisión clínica a la semana 10. |
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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) |
1) The proportion of patients with clinical response at Week 6 and Week 10 2) The proportion of patients in clinical remission at Week 6 3) The proportion of patients who achieve an endoscopic score and rectal bleeding score of 0 |
1) proporción de pacientes con respuesta clínica en semana 6 y semana 10 2) proporción de pacientes en remisión clínica en semana 6 3) proporción de pacientes que alcanzan resultado endoscopico y de hemorragia rectal de 0 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Week 6 and Week 10 2) Week 6 3) Week 10 |
1) semana 6 y semana 10 2) semana 6 3) semana 10 |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 |
Australia |
Canada |
Israel |
New Zealand |
United States |
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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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The CSR will be written following the end of treatment phase (when the last patient completes the Week 28 visit), this would be a total of thirteen months duration. However, patients will continue to be seen for an additional 17 months for PML follow-up, which would be 2 years 6 months total duration. At that point, the PML report will be submitted as an addendum to the CSR. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |