Resumen

Se trata de un estudio de fase 2, aleatorizado, doble ciego, controlado con placebo y de rango de dosis. El objetivo primario es evaluar la eficacia y la seguridad de SAR443122 en comparación con placebo en participantes con CU de moderada a grave. La selección de dosis para el desarrollo clínico ulterior se basará en múltiples parámetros de eficacia, seguridad y farmacocinética. El estudio consta de 4 brazos paralelos (3 grupos de dosis de SAR443122 versus placebo) para evaluar la eficacia y la seguridad de SAR443122 en participantes con CU de moderada a grave. Todos los participantes recibirán un total de 52 semanas de tratamiento del estudio (una fase de tratamiento de inducción de 12 semanas y una fase de mantenimiento de 40 semanas), salvo que el tratamiento deba discontinuarse según el criterio del investigador. Al finalizar las primeras 12 semanas de tratamiento de inducción, a todos los participantes con respuesta clínica o en remisión se les ofrecerá tratamiento del estudio durante hasta 40 semanas y continuarán con el mismo tratamiento enmascarado asignado. Los participantes que no logren respuesta clínica o remisión al finalizar las 12 semanas iniciales de tratamiento de inducción pasarán a un brazo de tratamiento abierto y recibirán SAR443122 a la dosis más alta evaluada. Además, los participantes de la fase de mantenimiento que pierdan eficacia clínica en cualquier momento hasta la V10/Semana 40 (semana 28 del mantenimiento) podrán pasar al brazo de tratamiento abierto con SAR443122 a la dosis más alta.

Descripción detallada

La duración total del estudio por participante será de hasta 58 semanas, incluyendo un período de selección de hasta 4 semanas, un período de tratamiento de hasta 52 semanas y un período de seguimiento postratamiento de 2 semanas.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 75 YearsSexo: ALL

Criterios de inclusión

Participants who have clinical evidence of active Ulcerative Colitis \[UC\] for ≥3 months before screening as confirmed by endoscopy during the screening period.
Participants must have a minimum disease extent of 15 centimeters from the anal verge.
Participants are inadequate or non-responders, have shown loss of response, or are intolerant to at least 1 of following approved treatments: amino-salicylate, corticosteroids, immunosuppressants or biologics other than natalizumab (Tysabri®) or small molecules.
Participants on corticosteroids must be on a stable dose ≥2 weeks prior to screening and during screening period.
Participants on methotrexate, azathioprine or 6- mercaptopurine must be on treatment for at least 8 weeks prior to screening; and on a stable dose ≥4 weeks prior to screening and during screening period.
Participants on oral 5-aminosalicylates, mesalamine or sulfasalazine must be on a stable dose for ≥4 weeks prior to screening and during screening period.
Participants on advanced therapies must have 1) last administration at least 5 half-lives prior to randomization, or 2) undetectable level of the biologic in their blood prior to randomization.
Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Women participants should not be pregnant or breastfeeding.

Criterios de exclusión

Participants with Crohn's Disease (CD).
Participants with diagnosis of indeterminate colitis or microscopic colitis.
Participants with stool sample positive for culture for aerobic pathogens or C difficile.
Participants with prior colectomy or anticipated colectomy during their participation in the study.
Participants with presence of ileal pouch or ostomy.
Participants with fulminant disease or toxic megacolon.
Participants with colonic dysplasia except for adenoma.
Participants with intestinal failure or short bowel syndrome requiring Total Parenteral Nutrition (TPN).
Participants with history of recurrent or recent serious infection that has not resolved within 4 weeks prior to randomization.
Participants presenting with active malignancies or recurrence of malignancy within the 5 years before screening.
Participants with a history or presence of another significant illness that according to the investigator's judgment would adversely affect the subject's ability to participate in this study.
Participants presenting with fever (≥38°C) or persistent chronic or active recurring infection within 4 weeks prior to the Screening Visit requiring treatment with antibiotics, antivirals, or any history of frequent recurrent infections deemed unacceptable per investigator's judgment.
Participants who were administered any live (attenuated) vaccine within 3 months prior to the randomization Visit.
Participants with a history of recurrent herpes zoster.
Participants with uncontrolled diabetes, defined as HbA1c ≥9.0% at the Screening Visit.
Participants with active tuberculosis (TB) or non-tuberculous mycobacterial infection, or a history of incompletely treated active or latent TB per local guidelines will be excluded from the study unless it is documented by a specialist that the participant has been adequately treated and can now start treatment with the RIPK1 kinase inhibitor.
Participants presenting with opportunistic infections within six months prior to screening or while receiving anti-TNF treatment in the last 6 months.
Participants undergoing hemodialysis or peritoneal dialysis.
Participants with a known history of Human Immunodeficiency Virus (HIV) infection or positive HIV serology at screening.
Participants with Positive Hepatitis B surface antigen (HBsAg) or positive Hepatitis B core antibody (HBcAb); and/or positive Hepatitis C antibody (HCV) at the Screening Visit. Participants that were treated for HCV and clear the virus documented by HCV RNA by PCR below the limit of quantification can be eligible.
Positive COVID-19 test, suspected COVID-19 infection or known exposure to COVID-19 during the screening period.
History of COVID-19 infection within 4 weeks prior to Screening; history of mechanical ventilation or extracorporeal membrane oxygenation (ECMO) due to COVID-19 infection within 3 months prior to Screening or with residual significant complications from COVID-19 making it unsafe for the participant to enter this study.
Participants presenting alcohol or drug dependency within the 2 years prior to the Screening Visit.
Participants with unexplained, uncontrolled, or untreated thyroid disease or unexplained abnormal serum prolactin levels at screening.
Participants under cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide or tacrolimus treatment within 4 weeks prior to screening.
Participants with previous exposure to natalizumab (Tysabri®).
Participants with previous exposure to RIPK1 inhibitor.
Participants under antidiarrheals within 2 weeks prior to screening and during screening period.
Participants under prednisone \>25 mg/day (or equivalent).
Participants under budesonide \>9 mg/day.
Participants who received intravenous corticosteroids or cytapheresis therapy within 2 weeks prior to screening or during screening.
Participants who were rectally administered topical 5-aminosalicylate or corticosteroids within 4 weeks prior to screening.
Participants who received therapeutic enema or suppository, other than required for colonoscopy or flexible sigmoidoscopy within 4 weeks prior to screening or during screening.
Participants who received antibiotics for UC or gastrointestinal infection within 4 weeks prior to screening.
Participants who have taken other investigational medications within 2 months or 5 half--lives, (whichever is longer) prior to screening.
Presence of significant laboratory findings at the Screening Visit.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ubicaciones

Investigational Site Number : 0320006

CABA, Buenos Aires, Argentina

Investigational Site Number : 0320003

Rosario, Santa Fe Province, Argentina

Investigational Site Number : 0320001

San Miguel de Tucumán, Tucumán Province, Argentina

Investigational Site Number : 0320002

Buenos Aires, Argentina

Investigational Site Number : 0320004

Córdoba, Argentina

Investigational Site Number : 0320005

Córdoba, Argentina

Investigational Site Number : 0320007

Salta, Argentina

Estudio aleatorizado, doble ciego, controlado con placebo y de búsqueda de dosis para evaluar la eficacia y la seguridad de SAR443122 en pacientes adultos con colitis ulcerosa de moderada a grave