Resumen

El propósito de este estudio es determinar si el medicamento en investigación LY3471851 es seguro y eficaz en participantes adultos con colitis ulcerosa (CU) activa. El tratamiento del estudio tendrá una duración de aproximadamente 52 semanas.

Descripción detallada

En la etapa 1, se compararán dos dosis (alta y baja) de LY3471851 con placebo. En la etapa 2, se compararán hasta dos dosis adicionales (a confirmar) de LY3471851 con placebo. LY3471851 (NKTR-358) es un potencial terapéutico de primera clase que puede abordar un desequilibrio subyacente del sistema inmunológico en personas con diversas enfermedades autoinmunes. Su mecanismo de acción se dirige al complejo receptor de interleucina (IL-2) en el organismo con el fin de estimular la proliferación de células inmunológicas inhibidoras conocidas como células T reguladoras. Al activar estas células, LY3471851 podría actuar para restaurar el equilibrio del sistema inmunológico.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 75 YearsSexo: ALL

Criterios de inclusión

Have moderately to severely active ulcerative colitis (UC) as defined by a modified Mayo score (MMS) of 4 to 9 with an endoscopic subscore (ES) ≥2, with endoscopy performed within 14 days before baseline.
Have evidence of UC extending proximal to the rectum (with ≥15 centimeters (cm) of involved colon).
Have up-to-date colorectal cancer surveillance performed according to local standard.
Participants are either one of the following:
Have failed conventional treatments including inability to tolerate oral or intravenous corticosteroids or immunomodulators (6-mercaptopurine or azathioprine or methotrexate), or history of corticosteroid dependence (an inability to successfully taper corticosteroids without return of UC) and neither failed or demonstrated intolerance to advanced therapy (eg, tumor necrosis factor (TNF) antagonists, anti-integrin therapies, anti-IL12/23p40 therapies, Janus kinase (JAK) inhibitor) OR,
Have failed advanced therapies such as treatment with 1 or more advance therapies (eg, tumor necrosis factor \[TNF\] antagonists, anti-integrin therapies, anti-IL12/23p40 therapies, Janus kinase \[JAK\] inhibitor) at doses approved for the treatment of UC with documented history of failure to respond to or tolerate such treatment.
Have had an established diagnosis of UC of ≥3 months in duration before baseline which includes endoscopic evidence of UC and a histopathology report that supports a diagnosis of UC. Supportive endoscopy and histopathology reports must be available in the source documents.
Women of child-bearing potential (WOCBP) must test negative for pregnancy as indicated by a negative serum pregnancy test at the screening visit followed by a negative urine pregnancy test within 24 hours prior to first exposure to study drug.

Criterios de exclusión

Have been diagnosed with indeterminant colitis, proctitis (colitis limited to the rectum only; less than 15 centimeter (cm) from the anal verge or Crohn's disease.
Have received any of the following for treatment of UC: cyclosporine, tacrolimus, mycophenolate mofetil or thalidomide within 2 weeks of screening, rectally administered corticosteroids or 5-aminosalicylic acid treatments within 2 weeks of screening.
Have had or will need abdominal surgery for UC (for example, subtotal colectomy).
Have failed 3 or more classes of advanced therapies approved for treatment of UC (eg, tumor necrosis factor \[TNF\] antagonists, anti-integrin therapies, anti-IL12/23p40 therapies, Janus kinase \[JAK\] inhibitor).
Have evidence of toxic megacolon, intra-abdominal abscess, or stricture/stenosis within the small bowel or colon.
Have any history or evidence of cancer of the gastrointestinal tract
Have myocardial infarction, unstable ischemic heart disease, stroke or heart failure within 12 months prior to screening.

Ubicaciones

DOM- Centro de Reumatologia

CABA, Buenos Aires, Argentina

Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno" CEMIC

CABA, Buenos Aires, Argentina

Mautalen Salud e Investigacion-Centro de Osteopatías Médicas

Ciudad Autonoma de Buenos Air, Buenos Aires, Argentina

Centro Médico Privado de Reumatología

San Miguel de Tucumán, Argentina

Estudio adaptativo de fase 2, aleatorizado, doble ciego, controlado con placebo de LY3471851 (NKTR 358) en pacientes con colitis ulcerosa moderadamente a gravemente activa