A Study of JNJ-64304500 as Add-on Therapy in Participants With Active Crohn's Disease

The purpose of this study is to evaluate the efficacy and safety of JNJ-64304500 as add-on therapy to standard of care (SOC) biologic treatment with anti-tumor necrosis factor alpha or anti-interleukin 12/23 inhibitors in participants with active Crohn's disease in response but not remission to SOC biologic therapy.

Biologic agents such as anti-tumor necrosis factor (TNF) and interleukin (IL)-12/23 antagonists have become the standard of care (SOC) in the treatment of patients with Crohn's disease. However, many patients fail to fully respond to treatment. This study will evaluate the efficacy of 10 week add on treatment with JNJ-64304500, compared to placebo, in patients taking SOC anti-TNF or anti-IL12/23 biologics. The study consists of a screening phase (up to 8 weeks); treatment phase (up to 12 weeks and follow-up phase (up to 16 weeks after the last administration of study agent). The total study duration will be up to 34 weeks. Key safety assessments include adverse events, clinical laboratory tests (hematology and chemistry), vital signs, monitoring for injection-site and hypersensitivity reactions, and early detection of active tuberculosis.

Eligibility Criteria:
Inclusion Criteria:

* Have confirmed clinical diagnosis of Crohn's disease or fistulizing Crohn's disease of at least 3 months' duration
* Initiated standard of care (SOC) biologic therapy for at least 12 uninterrupted weeks (including the induction dose) prior to Week 0 and agree to continue to maintain their SOC biologic with no change in dose level or interruption for the duration of the study. Adalimumab (including HUMIRA or an equivalent biosimilar which could include: HULIO, HYRIMOZ, IMRALDI, or AMGEVITA) at maintenance dose of 40 milligram (mg) subcutaneous (SC) every 2 weeks (q2w) plus minus (+ -) 4 days or Ustekinumab at maintenance dose of 90 mg SC every 8 weeks (q8w) + - 7 days
* Have active Crohn's disease (CD), with a baseline crohn's disease activity index (CDAI) score of greater than or equal to (\>=) 180 but less than or equal to (\<=) 400
* Participant with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age greater than (\>) 50 years, or other known risk factor must be up-to-date on colorectal cancer surveillance
* Participant who has had extensive colitis for \>=8 years, or disease limited to the left side of the colon for \>=12 years, must either have had a colonoscopy to assess for the presence of dysplasia within 1 year before the first administration of study agent or a colonoscopy to assess for the presence of malignancy at the screening visit, with no evidence of malignancy
* A woman of childbearing potential must have a negative highly sensitive serum (beta- human chorionic gonadotropin \[beta-hCG\]) pregnancy test result at screening and a negative urine pregnancy test result at Week 0 and throughout the study

Exclusion Criteria:

* Has complications of Crohn's disease as defined in study protocol
* Currently has or is suspected to have an abscess
* Concomitant or previous medical therapies received: has previously demonstrated suboptimal response, loss of response, or intolerance to more than 2 approved advanced therapies
* Concomitant or previous medical therapies received: corticosteroids and 5-aminosalicylic acid (5-ASA) compounds at unstable or above recommended doses are not permitted. Individuals receiving stable doses (oral corticosteroids at a prednisone-equivalent dose at or below 20 mg/day, or 6 mg/day of budesonide, 2.5 mg/day beclomethasone dipropionate, or at or below 5-ASA doses of 1.5 gram (g)/day) or if individuals have been discontinued, for at least 2 weeks before start of first study intervention (Week 0), are permitted
* Concomitant or previous medical therapies received: has received any of the following prescribed medications or therapies within the specified period or has plans to initiate throughout the study: conventional immunomodulators (that is , azathioprine \[AZA\], 6-mercaptopurine \[6 MP\], or methotrexate \[MTX\]) within 4 weeks of first dose of study intervention; oral immunomodulatory agents (example, 6-thioguanine \[6-TG\], cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil, tofacitinib and other Janus kinase \[JAK\] inhibitors \[including investigational JAK inhibitors\]) less than (\<) 6 weeks or within 5 half-lives of agent before first dose of SOC biologic, whichever is longer; all other immunomodulatory biologic agents (including investigational biologics) received within 12 weeks or within 5 half-lives of first dose of SOC biologic, whichever is longer
* Infections or predisposition to infections criteria: has a stool culture or other examination positive for an enteric pathogen, including clostridium difficile toxin, in the last 4 months unless a repeat examination is negative and there are no signs of ongoing infection with that pathogen
* Has a transplanted organ (with exception of a corneal transplant that needs to have occurred \> 12 weeks before screening)