Sanofi has initiated a clinical trial to evaluate the efficacy and safety of SAR441566 in patients with moderate-to-severe ulcerative colitis, targeting a patient population with significant unmet medical needs who have failed multiple prior therapies.
Trial Design and Patient Population
The study enrolls male and female participants aged 18 to 75 years who have clinical evidence of active ulcerative colitis for at least 3 months before screening, confirmed by endoscopy during the screening period. Eligible patients must present with active moderate-to-severe ulcerative colitis at screening, defined by a modified Mayo Score of 5 to 9 without the Physician Global Assessment.
Specific disease activity requirements include a minimum rectal bleeding subscore of 1, a minimum stool frequency subscore of 1, a modified Mayo Endoscopic Subscore of 2 or higher confirmed by central reader, a minimum sum of all subscores of 5, and disease extent greater than 15 cm from the anal verge.
Prior Treatment Requirements
The trial targets two distinct patient populations based on their treatment history. The first group includes patients with no prior exposure to advanced therapy but who have demonstrated inadequate response to, loss of response to, or intolerance to standard treatments including 5-ASA, 6-MP, AZA, MTX, oral or intravenous corticosteroids, or have a history of corticosteroid dependence defined as an inability to successfully taper corticosteroids without recurrence of ulcerative colitis.
The second group comprises patients who have shown inadequate response to, loss of response to, or intolerance to treatment with one or more approved advanced therapies. These include biologic agents such as TNF antagonists, anti-integrin agents other than natalizumab, anti-IL-12/23, anti-IL-23, or experimental biologic ulcerative colitis therapeutics, as well as small molecules such as JAK inhibitors or S1P receptor modulators.
Safety Exclusions and Monitoring
The trial implements comprehensive exclusion criteria to ensure patient safety. Participants with active Crohn's disease, indeterminate colitis, ischemic colitis, or microscopic colitis are excluded, as are those with ongoing complications of ulcerative colitis including fulminant colitis, toxic megacolon, or any manifestation that might require bowel surgery during study enrollment.
Patients with prior colectomy, ostomy, ileoanal pouch, or anticipated colectomy during study participation are ineligible. The protocol also excludes participants with fecal samples positive for ova or parasites, bacterial pathogens, or positive for Clostridium difficile B toxin in stools.
Infection and Malignancy Screening
Strict infection screening protocols exclude patients with active tuberculosis or a history of incompletely treated active or latent TB infection per local guidelines. Participants with positive Hepatitis B surface antigen, Hepatitis B core antibody, and/or Hepatitis C virus antibody at screening are excluded, as are those with any other active, chronic, or recurrent infections, including recurrent or disseminated herpes zoster or disseminated herpes simplex.
The trial excludes participants with known HIV infection or positive HIV-1 or HIV-2 serology at screening, as well as those presenting with active malignancies, lymphoproliferative disease, or recurrence of either within 5 years before screening.
Cancer Surveillance Requirements
For participants with extensive colitis for 8 years or more, or disease limited to the left side of colon for more than 10 years, a colonoscopy within 1 year of the screening visit is required to survey for dysplasia. Participants with dysplasia or cancer identified on biopsies are excluded from the study.
Medication Restrictions
The protocol establishes specific washout periods for various medications. Participants who received cyclosporine, tacrolimus, mycophenolate mofetil, or thalidomide within 30 days prior to screening are excluded, as are those who received fecal microbial transplantation within the same timeframe.
Patients with any prior exposure to natalizumab or oral carotegrast methyl are permanently excluded from participation. Additionally, participants who received IV corticosteroids within 14 days prior to screening or during the screening period are ineligible.
