Resumen

El propósito de este protocolo es evaluar la eficacia de tulisokibart en participantes con colitis ulcerosa (CU) moderadamente a gravemente activa. Las hipótesis primarias del Estudio 1 son que al menos 1 nivel de dosis de tulisokibart es superior al placebo en la proporción de participantes que alcanzan la remisión clínica según el Puntaje de Mayo Modificado en la Semana 12, y que al menos 1 nivel de dosis de tulisokibart es superior al placebo en la proporción de participantes que alcanzan la remisión clínica según el Puntaje de Mayo Modificado en la Semana 52. La hipótesis primaria del Estudio 2 es que al menos 1 nivel de dosis de tulisokibart es superior al placebo en la proporción de participantes que alcanzan la remisión clínica según el Puntaje de Mayo Modificado en la Semana 12.

Descripción detallada

El protocolo consta de 2 estudios. El Estudio 1 incluye tratamiento de inducción y de mantenimiento, y el Estudio 2 incluye solo tratamiento de inducción. Cada estudio tiene sus propias hipótesis y medidas de resultado que se evaluarán de forma independiente.

Elegibilidad

Edad mínima: 16 YearsEdad máxima: 80 YearsSexo: ALL

Criterios de inclusión

Has had ulcerative colitis (UC) (from onset of symptoms) for at least 3 months before randomization
Has moderately to severely active UC
Weight ≥40 kg
Satisfies at least 1 of the following criteria:
Has had an inadequate response or loss of response to 1 or more protocol-specified UC treatments
Protocol specified corticosteroid dependence
Has been intolerant to 1 or more protocol-specified UC treatments
Is on treatment with any protocol-specified drugs during the study and meets drug stabilization requirements, as applicable
Adolescent participants ≥16 and \<18 years of age can participate if approved by the country or regulatory/health authority
A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding and Is not a participant of childbearing potential (POCBP); or is a POCBP and uses an acceptable contraceptive method, or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention, medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy

Criterios de exclusión

Has a diagnosis of Crohn's Disease (CD) or indeterminate colitis (inflammatory bowel disease (IBD)-undefined) or other types of colitis or enteritis that may confound efficacy assessment.
Has a current diagnosis of fulminant colitis and/or toxic megacolon
Has UC limited to the rectum (i.e, must have evidence of UC extending beyond the rectosigmoid junction, which is \~10 cm from the anal margin)
Has a current or impending need for colostomy or ileostomy
Has had a total proctocolectomy or partial colectomy
Has received fecal microbial transplantation within 4 weeks before randomization
Has had UC exacerbation requiring hospitalization within 2 weeks before screening
Has prior or current evidence of definite colonic dysplasia except for low-grade dysplasia that has been completely removed
Has any active or serious infections without resolution after adequate treatment
Has had cytomegalovirus infection that resolved less than 4 weeks before screening
Has a transplanted organ which requires continued immunosuppression
Has a history of cancer (except fully treated non-melanoma skin cell cancers or cervical carcinoma in situ after complete surgical removal) within the last 5 years
Is known to be infected with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
Has evidence of active tuberculosis (TB), latent TB not successfully treated (per local guidelines), or inadequately treated TB (for participants with history of TB)
Has confirmed or suspected COVID-19
Has a history of drug or alcohol abuse within 6 months prior to screening
Has had major surgery within 3 months before screening or has a major surgery planned during the study
Is currently receiving or is planning to receive total parenteral nutrition at any time during study treatment
Has received UC-related antibiotics and has not been on stable doses for at least 14 days before randomization or has discontinued these medications within 14 days of randomization
Requires treatment with a therapy that does not adhere to the protocol-specified guidance parameters
Has received protocol-specified prohibited medications
Has had prior exposure to tulisokibart or another anti-tumor necrosis factor-like cytokine 1A (TL1A) antibody

Intervenciones

drug

IV Tulisokibart

Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously

drug

IV Placebo

Placebo matching IV tulisokibart

drug

SC Tulisokibart

Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously

drug

SC Placebo

Placebo matching SC tulisokibart

Ubicaciones

Centro de Investigaciones Médicas Mar del Plata ( Site 2101)

Mar del Plata, Buenos Aires, Argentina

CER medical Institute-Gastroenterology ( Site 2110)

Quilmes, Buenos Aires F.D., Argentina

Hospital Provincial del Centenario ( Site 2108)

Rosario, Santa Fe Province, Argentina

C.I.C.E. 9 de Julio-CICE 9 DE JULIO ( Site 2103)

San Miguel de Tucumán, Tucumán Province, Argentina

Programa de fase 3, aleatorizado, doble ciego y controlado con placebo para evaluar la eficacia y seguridad de MK-7240 en participantes con colitis ulcerosa moderadamente a gravemente activa

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

IV Tulisokibart

IV Placebo

SC Tulisokibart

SC Placebo

Ubicaciones

Centro de Investigaciones Médicas Mar del Plata ( Site 2101)

CER medical Institute-Gastroenterology ( Site 2110)

Hospital Provincial del Centenario ( Site 2108)

C.I.C.E. 9 de Julio-CICE 9 DE JULIO ( Site 2103)

Patrocinadores