A Study Evaluating Participants With Moderately to Severely Active Crohn's Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of JNJ-active as measured by the change in the Crohn's Disease Activity Index (CDAI) score and Simplified Endoscopic Score for Crohn's disease (SES-CD) from baseline at Week 12.

Official Title
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A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Platform Study Evaluating the Efficacy and Safety of Interventions in Participants With Moderately to Severely Active Crohn's Disease

Conditions
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Crohn Disease

Intervention / Treatment
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* Drug: JNJ-67864238
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have active Crohn's disease, defined as a baseline Crohn's Disease Activity Index (CDAI) score of greater than or equal to (>=) 220 and less than or equal to (<=) 450 Have evidence of active ileocolonic Crohn's disease as assessed by an Simplified Endoscopic Score for Crohn's disease (SES-CD) score >=3 at screening by central endoscopy reading; or an elevated screening C-reactive protein (CRP) (greater than [>] 0.3 milligrams per deciliter [mg/dL] or 3.0 milligrams per liter [mg/L]) or an elevated screening fecal calprotectin (>250 micrograms per mg [mcg/mg]) A participant with a family history of colorectal cancer, personal history of increased risk of colorectal cancer, age > 50 years, or other known risk factor must be up-to-date on colorectal cancer surveillance (may be performed during screening). Adenomatous polyps must be removed before the first administration of the study intervention 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 Has previously demonstrated inadequate response to, loss of response to, or intolerance to an approved biologic therapy (unless otherwise specified in the JNJ-67864238 intervention cohort specific criteria, that is, anti-tumor necrosis factor (TNF) alpha agents (for example, infliximab, adalimumab, certolizumab pegol], anti- interleukin (IL)-12/23 agents [for example, ustekinumab], or anti-integrin agents [for example, vedolizumab]) or has previously demonstrated an inadequate response to or failed to tolerate corticosteroids or immunomodulators (that is, 6-mercaptopurine [6-MP], azathioprine [AZA], and methotrexate [MTX]) but not a biologic, that is, the biologic nonfailures (Bio-NF) population Therapy for the treatment of Crohn's disease must include at least 1 of the following medications, which should have been maintained at stable doses prior to the baseline (Week 0) visit: (a) Oral 5-aminosalicylic acid (5-ASA) compounds; (b) Oral corticosteroids at a prednisone-equivalent dose <= 25 milligrams per day (mg/day), or 9 mg/day of budesonide, or 5 mg/day beclomethasone dipropionate; (c) Antibiotics being used as a primary treatment of Crohn's disease; and (d) Conventional immunomodulators (that is, AZA, 6-MP, or MTX) if participants have been taking them for at least 12 weeks and have been at a stable dose for at least 4 weeks prior to baseline Exclusion Criteria: Prior exposure to an anti-IL-12/23 (that is ustekinumab) or anti-IL-23 agents or related compound (including risankizumab, brazikumab, guselkumab, mirikizumab, and related compounds). Exception is made for participants who have had minimal exposure to ustekinumab at its approved labeled dosage and have met the required wash-out criteria and have not demonstrated inadequate response or intolerance to ustekinumab Known allergies, hypersensitivity, or intolerance to JNJ-67864238 or its excipients Has complications of Crohn's disease such as symptomatic strictures or stenoses, short gut syndrome, or any other manifestation that might be anticipated to require surgery, 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 JNJ-67864238 Has had any kind of bowel resection within 6 months or any other intra-abdominal surgery within 3 months before baseline Initiation of total (complete) or partial (supplemental) parenteral nutrition administered through any indwelling catheter less than (<) 3 weeks before baseline or anticipated to require parenteral nutrition administered through an indwelling catheter during enrollment in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JNJ-67864238<br>Participants will receive oral tablets of JNJ-67864238 twice daily for 12 weeks. | Drug: JNJ-67864238<br>* Participants will receive oral tablets of JNJ-67864238 twice daily.<br>|
| Placebo Comparator: Placebo<br>Participants will receive oral tablets of matching placebo twice daily for 12 weeks. | Drug: Placebo<br>* Participants will receive oral tablets of matching placebo twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Crohn's Disease Activity Index (CDAI) Score at Week 12 | CDAI is a validated measure of illness severity derived as sum of 8 different Crohn's disease (CD)-related variables (extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools, abdominal pain/cramping, use of antidiarrheal drug(s)/opiates, and general well-being). Last 3 variables were scored over 7 days by participant on diary card. Score ranges from 0 to 600; higher score=higher disease activities. Participants who had incomplete data (less than or equal to [<=]4 component values missing) at the visit, had their last available component value carried forward to calculate CDAI Score. Participants who had prohibited change in concomitant CD medication, CD-related surgery or discontinued intervention due to lack of efficacy or adverse event of worsening CD prior to Week 12 had their baseline value carried forward. Participants who had discontinuation of intervention due to corona virus disease-19 related reasons had their CDAI data as missing. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Simplified Endoscopic Score for Crohn's Disease (SES-CD) at Week 12 | SES-CD scoring system assesses disease severity in participants with CD. It is based on evaluation of 4 endoscopic components (presence/size of ulcers, proportion of mucosal surface covered by ulcers, proportion of mucosal surface affected by any lesions and presence/type of narrowing [strictures/ stenosis clinically] across 5 predefined ileocolonic segments (ileum, right colon, transverse colon, left colon and rectum). Each component score= 0 to 3 for each segment, total score calculated as sum of all component scores for all segments. Maximum sub-score for narrowings=11 points. Total SES-CD score ranges=0 to 56, where higher scores=more severe disease. Participants who had prohibited change in concomitant CD medication, CD-related surgery or discontinued intervention due to lack of efficacy/AE of worsening CD prior to Week 12 had their baseline value carried forward. Participants who had discontinuation of intervention due to COVID-19 related reasons had their CDAI data as missing. | Baseline and Week 12 | 
| Percentage of Participants With Clinical Response at Week 12 | Percentage of participants with clinical response at Week 12 were reported. Clinical response is defined as a greater than or equal to (>=) 100-point reduction from baseline in CDAI score or CDAI score less than (<) 150. The CDAI is a validated multi-item measure of severity of illness derived as a weighted sum of 8 different Crohn's disease-related variables (extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools, abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well-being). The last 3 variables were scored over 7 days by the participant on a diary card. In general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. | Week 12 | 
| Percentage of Participants With Clinical Remission at Week 12 | Percentage of participants with clinical remission at Week 12 were reported. Clinical remission is defined as CDAI score <150. The CDAI is a validated multi-item measure of severity of illness derived as a weighted sum of 8 different Crohn's disease-related variables (extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools, abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well-being). The last 3 variables were scored over 7 days by the participant on a diary card. In general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. | Week 12 | 
| Percentage of Participants With Patient-reported Outcome (PRO)-2 Remission at Week 12 | Percentage of participants with PRO-2 remission at Week 12 were reported. PRO-2 remission is defined as abdominal pain (AP) mean daily score (AP component of the CDAI) <=1 and stool frequency (SF) mean daily score of <=3, that is, AP <=1 and SF <=3. PRO-2 is a composite index consisting of weighted scoring of both variables. PRO-2 scores range from 0 to no upper limit with higher scores indicating more severe disease. | Week 12 | 
| Percentage of Participants With Endoscopic Response at Week 12 | Endoscopic response is defined as at least 50 percent (%) improvement from baseline in SES-CD score. SES-CD scoring system assesses disease severity in participants with CD. It is based on evaluation of 4 endoscopic components (presence/size of ulcers, proportion of mucosal surface covered by ulcers, proportion of mucosal surface affected by any lesions and presence/type of narrowing [strictures/ stenosis clinically] across 5 predefined ileocolonic segments (ileum, right colon, transverse colon, left colon and rectum). Each component score=0 to 3 for each segment, total score calculated as sum of all component scores for all segments. Maximum sub-score for narrowings=11 points. Total SES-CD score range=0 to 56, where higher score=more severe disease. | Week 12 | 
| Percentage of Participants With Endoscopic Remission at Week 12 | Endoscopic remission defined as an SES-CD score of <=2. SES-CD scoring system assesses disease severity in participants with CD. It is based on evaluation of 4 endoscopic components (presence/size of ulcers, proportion of mucosal surface covered by ulcers, proportion of mucosal surface affected by any lesions and presence/type of narrowing [strictures/ stenosis clinically] across 5 predefined ileocolonic segments (ileum, right colon, transverse colon, left colon and rectum). Each component score=0 to 3 for each segment, total score calculated as sum of all component scores for all segments. Maximum sub-score for narrowings=11 points. Total SES-CD score range=0 to 56, where higher score=more severe disease. | Week 12 |