A study of JNJ-78934804 in participants with moderately to severely active Crohn's disease

INTERVENTION: Screening period (up to 6 weeks) and double‐blind treatment period (up to 48 weeks). Participants will be randomly (by chance) divided into the following groups: Experimental: JNJ‐78934804 Participants will receive a JNJ‐78934804 induction dose at weeks 0, 4, and 8, followed by a JNJ‐78934804 maintenance dose once every 4 weeks (q4w) starting at week 12. All participants who meet the rescue criteria will receive a JNJ‐78934804 induction dose at weeks 16, 20, and 24, followed by a JNJ‐78934804 maintenance dose q4w starting at week 28. Participants who complete the double‐blind treatment phase (Week 48) and who may benefit from continued study intervention in the opinion of the investigator will have the opportunity to enter the long‐term extension (LTE) phase. Active Comparator: Guselkumab Participants will receive a guselkumab induction dose at weeks 0, 4, and 8, followed by a guselkumab maintenance dose q4w starting at week 12. All participants who meet the rescue criteria will receive a JNJ‐78934804 induction dose at weeks 16, 20, and 24, followed by a JNJ‐78934804 maintenance dose q4w starting at week 28. Participants who complete the double‐blind treatment phase (Week 48) and who may benefit from continued study intervention in the opinion of the investigator will have the opportunity to enter the LTE phase. CONDITION: Crohn’s disease ; Digestive System PRIMARY OUTCOME: 1. Co‐primary outcome: Percentage of participants with clinical remission at week 48. Clinical remission is defined as a Crohn’s Disease Activity Index (CDAI) score <150.; 2. Co‐primary outcome: Percentage of participants with endoscopic remission at week 48. Endoscopic remission is defined as a Simple Endoscopic Score for Crohn’s Disease (SES‐CD) score of <=4 with at least a 2‐point reduction from baseline and no subscore greater than (>) 1 in any individual component. INCLUSION CRITERIA: 1. At the time of informed consent, must be =18 years of age 2. Have a diagnosis of Crohn's disease (CD) or fistulizing CD established >=12 weeks before screening including both endoscopic evidence and a histopathology report consistent with a diagnosis of CD 3. Have moderately to severely active CD based on Crohn’s Disease Activity Inde X(CDAI) criteria defined as a baseline CDAI >=220 but <=450 and either 3.1. Mean daily stool frequency (SF) count >= 4.0, based on the unweighted CDAI component of the number of liquid or very soft stools, or 3.2. Mean daily AP score >=2.0, based on the unweighted CDAI component of abdominal pain (AP) 4. Have moderately to severely active ileal and/or colonic CD as assessed by central review of the screening video ileocolonoscopy based on Simple Endoscopic Score for Crohn’s Disease (SES‐CD) criteria 5. Have an inadequate initial response, loss of response, or intolerance to previously approved systemic therapies SECONDARY OUTCOME: 1. Percentage of participants with deep remission at week 48. Deep remission (composite endpoint) is defined as achieving both clinical remission and endoscopic remission at Week 48 at the participant level. Clinical remission is defined as a CDAI score of <150 and endoscopic remission is defined as a SES‐CD score of <=4 with at least a 2‐point reduction from baseline and no subscore >1 in any individual component. ; 2. Percentage of Participants with corticosteroid‐free (90‐day) clinical remission at week 48. Corticosteroid‐free (90‐day) clinical remission at Week 48 is defined as clinical remission at Week 48 and not receiving corticosteroids for at least 90 days prior to Week 48. Clinical remission is defined as a CDAI score of <150.; 3. Percentage of participants with corticosteroid‐free (90‐day) patient‐reported outcome(s) (PRO‐2) remission at week 48, defined as an abdominal pain (AP) mean daily score <=1 and stool frequency (SF) mean daily score <=2.8, no worsening of AP or SF from baseline, and not receiving corticosteroids for at least 90 days prior to Week 48.; 4. Percentage of participants with sustained clinical remission, defined as clinical remission at Week 12 and Week 48. Clinical remission is defined as a CDAI score of <150. CDAI scores range from 0 to approximately 600.; 5. Percentage of participants with histologic‐endoscopic remission at week 48, defined as achieving a combination of histologic remission and endoscopic remission. Histologic remission is defined as absence of neutrophils from the mucosa (both lamina propria and epithelium), no crypt destruction, and no erosions, or ulcerations or granulation tissue as assessed by the Robarts Histopathology Index. Endoscopic remission is defined as a SES‐CD score of <=4 with at least a 2‐point reduction from baseline and no subscore > 1 in any individual component.; 6. Percentage of participants with Inflammatory Bowel Disease Questionnaire (IBDQ) responses at week 48. IBDQ response at Week 48 is defined as an improvement of at least 16 points in the IBDQ total score from baseline at Week 48.; 7. Percentage of participants with Patient‐Reported Outcomes Measurement Information System 29 (PROMIS‐29) Mental Component Summary Score (MCS) response at Week 48, defined as an improvement of at least 7 points in the PROMIS‐29 MCS score from baseline at Week 48. ; 8. Percentage of participants with clinical remission at week 12. Clinical remission at week 12 is defined as a CDAI score of <150 at week 12. ; 9. Percentage of participants with endoscopic response at week 12, defined as >50% improvement from baseline in SES‐CD score at week 12 or a decrease of at least 2 points in participants with a baseline score of 4 and isolated ileal disease.; 10. Number of participants with adverse events (AE) and serious AEs (SAEs). An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non‐investigational) product. An AE does not necessarily have a causal relationship with the intervention. An SAE is any untoward medical occurrence that at any dose results in death; is life‐threatening; requires inpatient hospitalization or prolongation of existing hospitalisation; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a suspected transmission of any infectious agent via a medicinal product; and is medically important.