An Active and Placebo-Controlled Study of Brazikumab in Participants With Moderately to Severely Active Crohn's Disease

Inclusion and Exclusion Criteria are the same for both Stage 1 and Stage 2; however,participants enrolled in Stage 1 will not be permitted to enroll in Stage 2. Inclusion Criteria:

1. At the time of signing the informed consent, the participant must be 18 to 80 years ofage, inclusive.
2. A diagnosis of ileal, ileocolonic, or colonic CD with an onset of symptoms for aminimum of 3 months prior to Screening as determined by the investigator based onclinical history, exclusion of other etiologies including infectious causes, andcharacteristic endoscopic and/or histologic findings.
3. Moderately to severely active CD defined by a CDAI score of 220 to 450 AND; CDAI LSFscore ≥ 5 OR CDAI AP score ≥ 2; AND SES-CD of at least 6
4. Participant had an inadequate response or intolerance to intervention withconventional treatment [oral aminosalicylates, oral CS, azathioprine, methotrexate, or 6-mercaptopurine], or prior biological treatment, or demonstrated CS dependence forthe treatment of CD. For participants who have previously used biological treatment, aparticipant may have failed up to 3 biologics that include up to 2 differentmechanisms of action.
5. Participants taking 5-aminosalicylates, Oral prednisone (or equivalent), Budesonide,Immunomodulators, Oral antibiotics, Immunomodulators, Probiotics must be at a stable dose.
6. Participant must have the QFT-TB test performed and meet the following TB criteria. A TB worksheet must also be completed:
7. Participant has no known history of active TB.
8. Participant has no known history of latent TB without completion of an appropriatecourse of intervention.
9. Meets 1 of the following acceptable TB test results: i. Negative QFT-TB obtained from central laboratory during Screening, OR ii. For a positiveQFT-TB test obtained during Screening from the central laboratory, active TB must be ruledout or treated and negative QFT-TB confirmed by central laboratory OR iii. IndeterminateQFT-TB test obtained during the Screening Period from the central laboratory with ongoingQFT-TB testing as outlined in Appendix G. Participants with an indeterminate QFT-TB testcan continue with Screening if they have all of the following:
10. no symptoms/risk factors per TB worksheet provided by the sponsor
11. no known recent exposure to a case of active TB
12. no evidence of active TB on chest x-ray within 8 weeks prior to Screening or duringScreening
13. confirmed QFT-TB negative by central laboratory

7 Female participants of childbearing potential must have a negative urine pregnancy testprior to administration of study intervention and must agree to use a highly effectivemethod of birth control (confirmed by the investigator) from randomization throughout thestudy duration and for at least 18 weeks after last dose of study intervention.

8 Women not of childbearing potential are defined as women who are either permanentlysterilized or who are postmenopausal. Women will be considered postmenopausal if they havebeen amenorrhoeic for 12 months prior to the planned date of randomization without analternative medical cause.

9 Nonsterilized males who are sexually active with a female partner of childbearingpotential must comply with the methods of contraception during treatment and until the endof relevant systemic exposure in the male participant, plus a further 18 weeks.

10 Capable of giving signed informed consent, which includes compliance with therequirements and restrictions listed in the ICF and in the protocol.

11 Willingness and ability to attend all study visits, comply with the study procedures,read and write in order to complete questionnaires, and be able to complete the studyperiod.

12 Provision of signed and dated written Optional Genetic Research Information informedconsent prior to collection of samples for optional genetic research that supports GenomicInitiative. Complete inclusion criteria are in the study protocol

Exclusion Criteria:

1. Participant is unable or unwilling to have endoscopic procedures performed during thestudy.
2. History or current diagnosis of ulcerative colitis, indeterminate colitis, microscopiccolitis, ischemic colitis, colonic mucosal dysplasia, primary sclerosing cholangitis,or untreated bile acid malabsorption.
3. History of toxic megacolon within 3 months prior to Randomization.
4. Any intra-abdominal surgery, bowel resection, diversion, placement of ostomy or stomawithin 3 months prior to Screening. Participants with a draining stoma, ostomy, orextensive colonic resection are excluded irrespective of the time from surgery.
5. Participant has an enterocutaneous or enterovesicular fistula. Participants with otheractive fistulas, including perianal fistulas, may be considered for enrollment ifthere is no anticipation for surgery and there is no evidence of active infection (eg,abscess).
6. Bowel perforation during the 6 months prior to Screening or evidence of obstructionwithin 3 months of Screening.
7. Complications of CD including short bowel syndrome, strictures/stenoses withobstruction or pre-stenotic dilation, or conditions where surgery may be anticipatedwithin 6 months, or other conditions that may confound efficacy evaluations for thestudy.
8. Participant has any non-passable colonic stenosis/narrowing identified during thequalifying ileocolonoscopy (successful endoscope passage to the caecum with inabilityto enter the endoscope into the ileum is not covered under this exclusion criterion,and does not require exclusion).
9. Ongoing nutritional dependency for total parenteral nutrition or an elemental diet atScreening.
10. Participant has any of the following related to infections: • Evidence of a recent (within 6 months of Randomization) systemic fungal infection, requiring inpatienthospitalization, and/or antifungal treatment. • Any infection requiringhospitalization or treatment with IV anti-infectives (including antiviral treatment)within 4 weeks of Screening. • Cytomegalovirus or Epstein-Barr virus infection thathas not resolved within 8 weeks prior to Screening • Clinically significant chronicinfection (eg, osteomyelitis) that has not resolved within 8 weeks of Screening •Nonserious infection requiring oral anti-infectives within 2 weeks prior torandomization must be further discussed with the Study Physician/designee. •Participant has clinical evidence of or suspected to have an abscess during Screening. • Diagnosis of peritonitis or receiving treatment for peritonitis within 8 weeks priorto Screening • Participant has any underlying condition that predisposes participantto infections • Clinically significant active infection or signs/symptoms of infectionthat has the potential to worsen with immunosuppressive therapy • Signs or symptoms ofongoing infection due to intestinal pathogens
11. Previous allogenic bone marrow transplant or history of organ or cell-basedtransplantation (eg, islet cell transplantation or autologous stem celltransplantation) with the exception of corneal transplant.
12. Chronic hepatitis B or C infection.
13. Known history of primary immunodeficiency, splenectomy, or any underlying conditionthat predisposes the subject to infection, includingHIV infection.
14. Prior history of or current diagnosis of a demyelinating disorder.
15. Participant has received the following treatment: • Adalimumab, certolizumab pegol,infliximab, or golimumab: within 8 weeks prior to Randomization • Vedolizumab orustekinumab within 12 weeks prior to Randomization • Other prohibited medication,biologic or small molecule treatment within 5 half-lives prior to Randomization •Fecal microbiota transplantation: within 8 weeks prior to Screening ileocolonoscopy
16. Except for ustekinumab, prior exposure to any biologic agent targeting IL-12 or IL-23.
17. Participants who received cyclosporine, mycophenolate mofetil, sirolimus (rapamycin),thalidomide, tacrolimus (FK-506), or tofacitinib within 2 weeks prior to ScreeningVisit 1.
18. Known history of allergy to the study intervention formulation or any of itsexcipients or components of the delivery device, or to any other biologic therapy.
19. Participants received more than 1 dose of IV or intramuscular steroids within 2 weeksprior to Screening Visit 1.
20. Participant received topical (rectal) aminosalicylic acid (eg, mesalamine) or topical (rectal) steroids within 2 weeks prior to Randomization.
21. Participant received a Bacille Calmette-Guérin vaccination within 12 months ofRandomization or any other live vaccine less than 4 weeks prior to Randomization or isplanning to receive any such vaccine over the course of the study.
22. Participant has known or suspected history of chronic use of NSAIDs (defined as atleast 3 times per week for more than 3 months; not applicable to daily aspirin use upto 325mg per day) and/or opiates, drug, or alcohol abuse.
23. History of cancer with the following exceptions: (a) A history of basal cell carcinomaand/or squamous cell carcinoma of the skin, with apparent successful curative therapygreater than 12 months prior to Screening (b) Carcinoma in situ of the cervix, withapparent successful curative therapy, greater than 12 months prior to Screening.
24. Clinically significant cardiovascular conditions including recent myocardialinfarction, unstable angina, stroke, transient ischemic attack, decompensated heartfailure requiring hospitalization, or Class III/IV heart failure within 6 months ofScreening.
25. Prolonged QTcF interval (QTc >450 msec or QTC >480 for participants with bundle branchblock; determined on central ECG), or conditions leading to additional risk for QTprolongation (eg, congenital long-QT syndrome).
26. Clinically significant kidney disease
27. Abnormal laboratory results at Screening
28. Other concurrent medical conditions: Participant has known, preexisting, clinicallysignificant endocrine, autoimmune, metabolic, neurologic, renal, gastrointestinal,hepatic, hematological, respiratory or any other system abnormalities that are notassociated with CD and are uncontrolled with standard treatment.
29. Participant is currently enrolled in another investigational device or drug study, oris within 35 days or 5 half-lives, whichever is longer, since ending anotherinvestigational device or drug study, or receiving other investigational agent(s)
30. Transfusion of blood, plasma, or platelets within the 30 days prior to Screening.
31. Females who are pregnant, nursing, or planning a pregnancy during the study OR femaleswho are of childbearing potential and do not agree to use a highly effective method ofcontraception consistently and correctly.
32. Employees of the clinical study site or any other individuals involved with theconduct of the study, or immediate family members of such individuals.
33. Previous randomization in the present study. . Complete exclusion criteria are in thestudy protocol