Dose-finding Study of SAR443122 in Adult Participants With Ulcerative Colitis

Launched by SANOFI · Oct 17, 2022

Keywords

ClinConnect Summary

This clinical trial is testing a new medication called SAR443122 to see how well it works and how safe it is for adults with moderate to severe Ulcerative Colitis (UC), a condition that causes inflammation in the intestines. The study will compare SAR443122 to a placebo, which is a harmless substance that doesn't contain the active medication. Participants will be divided into four groups to receive different doses of SAR443122 or the placebo over a total of 52 weeks. The first 12 weeks will focus on getting participants to a better health status, and those who respond well will continue with the treatment for an additional 40 weeks.

To be eligible for this trial, participants must have had active UC for at least three months and must have not responded well to previous treatments. They should also be between the ages of 18 and 80 and meet other specific health criteria. Throughout the trial, participants can expect regular check-ups and monitoring of their health, and those who do not respond to the initial treatment will have the chance to receive the highest dose of SAR443122 in a different part of the study. This trial is currently recruiting participants, so if you or someone you know is interested, it’s a good idea to discuss it with a healthcare provider.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 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.
• Exclusion Criteria:
• • 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.