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.
1. At the time of signing the informed consent, the participant must be 18 to 80 years of
2. A diagnosis of ileal, ileocolonic, or colonic CD with an onset of symptoms for a
minimum of 3 months prior to Screening as determined by the investigator based on
clinical history, exclusion of other etiologies including infectious causes, and
characteristic endoscopic and/or histologic findings.
3. Moderately to severely active CD defined by a CDAI score of 220 to 450 AND; CDAI LSF
score ≥ 5 OR CDAI AP score ≥ 2; AND SES-CD of at least 6. 4. Participant had an inadequate response or intolerance to intervention with
conventional treatment [oral aminosalicylates, oral CS, azathioprine, methotrexate, or
6-mercaptopurine], or prior biological treatment, or demonstrated CS dependence for
the treatment of CD. For participants who have previously used biological treatment, a
participant may have failed up to 3 biologics that include up to 2 different
mechanisms of action.
5. Participants taking 5-aminosalicylates, Oral prednisone (or equivalent), Budesonide,
Immunomodulators, Oral antibiotics, Immunomodulators, Probiotics must be at a stable
6. Participant must have the QFT-TB test performed and meet the following TB criteria.
A TB worksheet must also be completed:
1. Participant has no known history of active TB.
2. Participant has no known history of latent TB without completion of an appropriate
course of intervention.
3. Meets 1 of the following acceptable TB test results:
i. Negative QFT-TB obtained from central laboratory during Screening, OR ii. For a positive
QFT-TB test obtained during Screening from the central laboratory, active TB must be ruled
out or treated and negative QFT-TB confirmed by central laboratory OR iii. Indeterminate
QFT-TB test obtained during the Screening Period from the central laboratory with ongoing
QFT-TB testing as outlined in Appendix G. Participants with an indeterminate QFT-TB test
can continue with Screening if they have all of the following:
1. no symptoms/risk factors per TB worksheet provided by the sponsor. 2. no known recent exposure to a case of active TB. 3. no evidence of active TB on chest x-ray within 8 weeks prior to Screening or during
Screening. 4. confirmed QFT-TB negative by central laboratory. 7 Female participants of childbearing potential must have a negative urine pregnancy test
prior to administration of study intervention and must agree to use a highly effective
method of birth control (confirmed by the investigator) from randomization throughout the
study 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 permanently
sterilized or who are postmenopausal. Women will be considered postmenopausal if they have
been amenorrhoeic for 12 months prior to the planned date of randomization without an
alternative medical cause.
9 Nonsterilized males who are sexually active with a female partner of childbearing
potential must comply with the methods of contraception during treatment and until the end
of relevant systemic exposure in the male participant, plus a further 18 weeks.
10 Capable of giving signed informed consent, which includes compliance with the
requirements 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 study
12 Provision of signed and dated written Optional Genetic Research Information informed
consent prior to collection of samples for optional genetic research that supports Genomic
Complete inclusion criteria are in the study protocol.
1. Participant is unable or unwilling to have endoscopic procedures performed during the
2. History or current diagnosis of ulcerative colitis, indeterminate colitis, microscopic
colitis, 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 stoma
within 3 months prior to Screening. Participants with a draining stoma, ostomy, or
extensive colonic resection are excluded irrespective of the time from surgery.
5. Participant has an enterocutaneous or enterovesicular fistula. Participants with other
active fistulas, including perianal fistulas, may be considered for enrollment if
there is no anticipation for surgery and there is no evidence of active infection (eg,
6. Bowel perforation during the 6 months prior to Screening or evidence of obstruction
within 3 months of Screening.
7. Complications of CD including short bowel syndrome, strictures/stenoses with
obstruction or pre-stenotic dilation, or conditions where surgery may be anticipated
within 6 months, or other conditions that may confound efficacy evaluations for the
8. Participant has any non-passable colonic stenosis/narrowing identified during the
qualifying ileocolonoscopy (successful endoscope passage to the caecum with inability
to 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 at
10. Participant has any of the following related to infections: • Evidence of a recent
(within 6 months of Randomization) systemic fungal infection, requiring inpatient
hospitalization, and/or antifungal treatment. • Any infection requiring
hospitalization or treatment with IV anti-infectives (including antiviral treatment)
within 4 weeks of Screening. • Cytomegalovirus or Epstein-Barr virus infection that
has not resolved within 8 weeks prior to Screening • Clinically significant chronic
infection (eg, osteomyelitis) that has not resolved within 8 weeks of Screening •
Nonserious infection requiring oral anti-infectives within 2 weeks prior to
randomization 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 prior
to Screening • Participant has any underlying condition that predisposes participant
to infections • Clinically significant active infection or signs/symptoms of infection
that has the potential to worsen with immunosuppressive therapy • Signs or symptoms of
ongoing infection due to intestinal pathogens. 11. Previous allogenic bone marrow transplant or history of organ or cell-based
transplantation (eg, islet cell transplantation or autologous stem cell
transplantation) with the exception of corneal transplant.
12. Chronic hepatitis B or C infection.
13. Known history of primary immunodeficiency, splenectomy, or any underlying condition
that 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 or
ustekinumab 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 Screening
18. Known history of allergy to the study intervention formulation or any of its
excipients 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 weeks
prior 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 of
Randomization or any other live vaccine less than 4 weeks prior to Randomization or is
planning 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 at
least 3 times per week for more than 3 months; not applicable to daily aspirin use up
to 325mg per day) and/or opiates, drug, or alcohol abuse.
23. History of cancer with the following exceptions: (a) A history of basal cell carcinoma
and/or squamous cell carcinoma of the skin, with apparent successful curative therapy
greater than 12 months prior to Screening (b) Carcinoma in situ of the cervix, with
apparent successful curative therapy, greater than 12 months prior to Screening.
24. Clinically significant cardiovascular conditions including recent myocardial
infarction, unstable angina, stroke, transient ischemic attack, decompensated heart
failure requiring hospitalization, or Class III/IV heart failure within 6 months of
25. Prolonged QTcF interval (QTc >450 msec or QTC >480 for participants with bundle branch
block; determined on central ECG), or conditions leading to additional risk for QT
prolongation (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, clinically
significant endocrine, autoimmune, metabolic, neurologic, renal, gastrointestinal,
hepatic, hematological, respiratory or any other system abnormalities that are not
associated with CD and are uncontrolled with standard treatment.
29. Participant is currently enrolled in another investigational device or drug study, or
is within 35 days or 5 half-lives, whichever is longer, since ending another
investigational 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 females
who are of childbearing potential and do not agree to use a highly effective method of
contraception consistently and correctly.
32. Employees of the clinical study site or any other individuals involved with the
conduct of the study, or immediate family members of such individuals.
33. Previous randomization in the present study. . Complete exclusion criteria are in the