Efficacy and Safety of Obefazimod in Subjects With Moderately to Severely Active Crohn's Disease

Inclusion Criteria:

1. Male or female (at birth) 18 to 75 years old and able to understand, sign, and datethe written voluntary informed consent at the visit prior to any protocol-specifiedprocedures

2. Able and willing to comply with study visits and procedures as per protocol.

3. Confirmed and documented diagnosis of CD based on endoscopy and histology reports.

4. Moderately to severely active CD as defined by 220 ≤ CDAI ≤ 450 and SES-CD ≥ 6 forileo-colonic or colonic disease or SES-CD ≥ 4 for isolated ileal disease (percentral reading).

5. Documented inadequate response (defined as lack of response or loss of response orintolerance) to at least one of the following treatments: corticosteroids (CS),immunosuppressants (IS), biologic or biosimilar therapies, or janus kinase (JAK) (note: failure to only 5-aminosalicylic acid [5-ASA] is not accepted)

6. Women of childbearing potential (WOCBP) and male subjects with WOCBP partner mustagree to comply with contraception requirements as stated in section 4.5 (contraception) of this protocol.

7. Subject should be affiliated to a health insurance policy whenever required by aparticipating country or state.

8. Subject is able and willing to comply with usual public recommendations for sunprotection.

Exclusion Criteria:

Subjects who meet any of the following exclusion criteria will be excluded from the study:

1. WOCBP subject who is pregnant or breast-feeding at screening, or intends to becomepregnant during the study; or male subject with WOCBP partner who intends to bepregnant during the study.

2. Current diagnosis of ulcerative colitis (UC) or indeterminate colitis

3. CD without ileal and/or colonic involvement

4. Untreated active external or perianal fistula or abscess. Stable fistula withoutabscess and with minimal or low drainage may be enrolled. Recent cutaneous andperianal abscesses are not exclusionary if drained and adequately treated at least 3weeks before screening colonoscopy or 8 weeks before screening colonoscopy forintra-abdominal abscesses, if no additional surgery is anticipated.

5. Symptomatic bowel stricture and/or stenosis not passable in endoscopy

6. Related to CD surgery:

7. Current stoma or ileoanal pouch

8. More than 2 missing complete segments of the following 5 segments: terminalileum, right colon, transverse colon, left colon, and sigmoid and rectum

9. Combined previous small bowel resections > 100 cm

10. Surgical bowel resection within the past 3 months prior to baseline

11. Any other manifestation that might require surgery while enrolled in the study

12. Related to CD treatments:

13. Subject who is currently treated with prohibited concomitant therapies for CDas described in the study protocol

14. Subject who has previously received natalizumab (or any other α4β1 integrinagonist)

15. Subject who has failed more than three advanced therapies for the treatment ofCD, or two different mechanisms of action for advanced therapies of CD

16. History of, or active, malignancy including nonmelanoma skin cancer (subjects with a 5-year disease-free survival are eligible)

17. History of colonic cancer or colonic low grade or high grade dysplasia adenomatouspolyps, and/or at the screening endoscopy, evidence of low grade or high gradedysplasia adenomatous polyps (fully removed or not)

18. Subject with history of, or diagnosed with, the following during screening: primarysclerosing cholangitis, autoimmune hepatitis, or primary biliary cirrhosis

19. Serious illness requiring hospitalization (not related to CD) within 4 weeks priorto screening

20. Subject with the following infectious conditions:

21. Chronic or recurrent Grade 3 or Grade 4 infection within the last 2 monthsprior to screening or history of opportunistic infection while not onimmunosuppressive therapy

22. Herpes zoster reactivation within the last 2 months prior to screening

23. Active infection at screening or any major episode of infection that requiredhospitalization or treatment with IV antibiotics within 1 month of screening orduring screening (fungal infection of nail beds is allowed)

24. Positive assay or stool culture for pathogens (ova and parasite examination,bacteria) that required treatment per local medical practice or positive testfor Clostridioides difficile (C. difficile) toxin at screening.

25. Subject with human immunodeficiency virus (HIV) infection

26. Acute or chronic hepatitis B infection at screening (positive for hepatitis Bsurface antigen [HbsAg] or negative for HbsAg and positive for anti-hepatitis Bcore antibody in conjunction with detectable hepatitis B virus [HBV]deoxyribonucleic acid [DNA], or detectable HBV DNA).

27. Acute or chronic hepatitis C virus (HCV) infection as defined by positive forhepatitis C antibody (subjects successfully treated and without recurrence ≥ 1year with no detectable HCV RNA [assessed centrally] are eligible)

28. Active tuberculosis (TB) or untreated latent TB (For subjects with positive orintermediate QuantiFERON test)

29. Subject with uncontrolled ischemic heart disease and/or a history of congestiveheart failure

30. Subject with a known family or personal history of congenital or acquired long QTsyndrome, or subjects with a marked baseline prolongation of QT/ heartrate-corrected QT (QTc) interval

31. Subject with a history of torsade de pointe (TdP)

32. Acute or chronic clinically relevant pulmonary, hepatic, or renal functionalabnormality, encephalopathy, neuropathy or unstable central nervous system pathologysuch as seizure disorder, or any other clinically significant medical problems.

33. Subjects who received live vaccine within 3 months prior to screening and/or subjectwho is planning to receive such a vaccine during the study duration

34. Acute or chronic pancreatitis

35. Subject with the following hematological and biochemical laboratory parametersobtained during the screening period:

36. Hemoglobin ≤ 8.0 g/dL1

37. Absolute neutrophil count < 750/mm3

38. Platelets < 100,000 /mm3

39. eGFR < 60 mL/min/1.73 m2

40. Total serum bilirubin > 1.5 x ULN (except if related to pre-existing anddocumented Gilbert syndrome)

41. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2 xULN

42. Subject who does not meet the washout period requirements prior to the screeningendoscopy as described in the prohibited medication section of the study protocol

43. Use of any investigational or nonregistered product within 3 months or within 5halflives preceding baseline, whichever is longer, and during the study.

44. Subjects previously treated with obefazimod or with a known hypersensitivity to theactive substance or to any of the excipients

45. Illicit drug or alcohol abuse or dependence

46. Subject who is committed to an institution by virtue of an order issued either bythe judicial or the administrative authorities

47. Any condition, which in the opinion of the investigator, could compromise thesubject's safety or adherence to the study protocol