Overview

This is a phase 2, multinational, multicenter, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of SAR441566 in adults with moderate to severe Crohn's Disease (CD). The primary objective of this study is to assess the efficacy of different doses of SAR441566 compared with placebo in participants with moderate to severe CD.

This study will have an anticipated duration of up to 59 weeks which will include a screening period of 4 weeks (+7 calendar days if needed), followed by the Main Study (MS) treatment period, lasting 52 weeks, and a 2-week follow-up period after end of treatment. The MS period includes a Double-Blind (DB) treatment period with 12 weeks of induction followed by 40 weeks of maintenance.

Additionally, an Open Label (OL) period of up to 40 weeks will be offered to eligible participants. The combined duration of the DB maintenance and OL periods cannot exceed 40 weeks, depending on when participants switch.

Eligibility

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

1. Male or female participants aged 18 to 75 years at the time of signing the ICF
2. Confirmed diagnosis of CD for at least 3 months prior to Baseline
3. Confirmed diagnosis of moderate to severe CD as assessed by:
   • Crohn's Disease Activity Index (CDAI) score and the Simple Endoscopic Score for Crohn's disease (SES-CD) on an endoscopy confirmed by a central reader
   • stool frequency (SF), abdominal pain (AP) score
4. History of prior exposure to standard treatment (5-ASA, steroids, immunomodulators

   or antibiotics) or advanced therapies (biologics or small molecules), but having inadequate response to, loss or response to or intolerance to at least one of these therapies

5. On stable doses of standard treatments prior to screening (Oral 5-ASA compounds, Oral corticosteroids, AZA, 6-MP, or MTX ..)
6. 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 are excluded from the study if any of the following criteria apply:

1. Participants with active UC, indeterminate colitis or short bowel syndrome
2. Participants with CD isolated to the stomach, duodenum, jejunum, or peri anal region, without colonic or ileal involvement
3. Participants with following ongoing known complications of CD: fistula, abscess, symptomatic stricture/stenosis, fulminant colitis, toxic megacolon, recent bowel resection within 3 months of screening or history of > 3 bowel resections
4. Participants with stool sample positive for infectious pathogens
5. Participants with active tuberculosis (TB) or a history of incompletely treated active or latent TB per local guidelines
6. 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
7. Participants with any other active, chronic or recurrent infection, including recurrent or disseminated herpes zoster or disseminated herpes simplex
8. Participants with a known history of Human Immunodeficiency Virus (HIV) infection or positive HIV-1 or HIV-2 serology at screening
9. Participants presenting with active malignancies, lymphoproliferative disease, or recurrence of either, within the 5 years before screening
10. History of colonic mucosal dysplasia or presence of colonic mucosal dysplasia or adenomatous colonic polyps not removed during colonoscopy at screening visit
11. Infection(s) requiring treatment with IV anti infectives within 30 days or oral/intramuscular anti-infectives within 14 days prior to the screening visit
12. Participants requiring or receiving any parental nutrition and/or exclusive enteral nutrition
13. Participants who received cyclosporine, tacrolimus, mycophenolate mofetil, or thalidomide within 30 days prior to screening
14. Participants who received fecal microbial transplantation within 30 days prior to screening
15. Participants who have ever been exposed to natalizumab (Tysabri®) or oral carotegrast methyl (Carogra®)
16. Participants who received IV corticosteroids within 14 days prior to screening or during screening period
17. Participants who received therapeutic enema or suppository, other than required for colonoscopy within 14 days prior to screening or during screening
18. Screening laboratory and other analyses show abnormal results