The purpose of this study is to assess how well guselkumab works when compared to risankizumab in participants with moderately to severely active Crohn's Disease (CD; a long-term condition causing severe inflammation of the intestinal tract).

Inclusion criteria:

• Has CD or fistulizing Crohn's Disease (CD) of at least 12 weeks' duration, with colitis, ileitis, or ileocolitis, confirmed at some time in the past by radiography, histology, and/or endoscopy

• Have moderately to severely active CD, defined as baseline Crohn's Disease Activity Index (CDAI) score greater than or equal to (>=) 220 but less than or equal to (<=) 450

• Baseline endoscopic evidence of active ileal and/or colonic CD as assessed by central endoscopy reading at the screening endoscopy defined as a screening Simple Endoscopic Score for Crohn's Disease (SES CD) >= 4 (for participants with isolated ileal disease) or >= 6 (for participants with colonic or ileocolonic disease), based on the presence of ulceration in any 1 of the 5 ileocolonic segments, resulting in the following specified ulceration component scores:

  1. a minimum score of 1 for the component of "size of ulcers" AND
  2. a minimum score of 1 for the component of "ulcerated surface"

• In the opinion of the investigator, participant's disease is appropriate to treat with the maintenance dosing regimens utilized in the study

• Adhere to the requirements for concomitant medications for the treatment of CD as mentioned in the protocol

Exclusion criteria

• Has complications of CD such as symptomatic strictures or stenoses, short gut syndrome, active draining stoma or significant fistulizing disease or any other manifestation anticipated to require surgery within the next year, could preclude the use of the CDAI to assess response to therapy, or would possibly confound the ability to assess the effect of treatment with guselkumab or risankizumab
• Currently has or is suspected to have an abscess
• Has an active fistula during screening or at Week 0 with an anticipated need for surgery
• Has had any kind of bowel resection within 24 weeks, or any other intra-abdominal or other major surgery within 12 weeks, before first dose of study intervention
• Currently has a malignancy or has a history of malignancy within 5 years before screening

The data sharing policy of Johnson & Johnson Innovative Medicine is available at www.innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu.