Safety and Efficacy Study of JNJ-64304500 in Participants With Moderately to Severely Active Crohn's Disease

Study Overview
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Brief Summary
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The purpose of the study is to assess the safety and efficacy of JNJ-64304500 in participants with moderately to severely active Crohn's disease.

Official Title
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A Phase 2b, Randomized, Double-Blind, Placebo Controlled, Parallel Group, Multicenter Study to Evaluate the Safety and Efficacy of JnJ-64304500 in Subjects With Moderately to Severely Active Crohn's Disease

Conditions
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Crohn Disease

Intervention / Treatment
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* Drug: JNJ-64304500
* Drug: Placebo
* Drug: Ustekinumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have Crohn's disease or fistulizing Crohn's disease of at least 3 months' duration, with colitis, ileitis, or ileocolitis, confirmed at any time in the past by radiography, histology, and/or endoscopy A woman of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [b-hCG]) pregnancy test result at screening and a negative urine pregnancy test result at Week 0 Adhere to the following requirements for concomitant medication for the treatment of Crohn's disease, which are permitted provided that doses meeting these requirements are stable, or have been discontinued, for at least 3 weeks before baseline (Week 0), unless otherwise specified: a) Oral 5-aminosalicylic acid (5-ASA) compounds, b) Oral corticosteroids at a prednisone-equivalent dose at or below 40 milligram 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, d) Conventional immunomodulators (that is, azathioprine (AZA), 6-mercaptopurine (6-MP), or Methotrexate (MTX)): participants must have been taking them for at least 12 weeks and at a stable dose for at least 4 weeks before baseline A participant who has had extensive colitis for greater than or equal to (>=) 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 Have active Crohn's disease, defined as a baseline Crohn's Disease Activity Index (CDAI) score of >= 220 but <= 450 Exclusion Criteria: Participants who have received intravenous (IV) corticosteroids less then (<)3 weeks or have received tumor necrosis factor-alpha (TNF-alpha) antagonist biologic agents (example, monoclonal antibody [mAb] therapies) or other agents intended to suppress or eliminate tumor necrosis factor-alpha (TNF-alpha) <8 weeks or have received Vedolizumab <16 weeks before the first administration of study drug Woman who is pregnant or planning pregnancy or is a man who plans to father while randomized in the study or within 16 weeks after the last administration of study agent Participants with certain complications of Crohn's disease that would make it hard to assess response to study drug Participants with a history of or ongoing chronic or recurrent infectious disease Has previously received a biologic agent targeting interleukin (IL)-12 or IL-23, including but not limited to ustekinumab or briakinumab (ABT-874)

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part I : Placebo<br>Participants will receive placebo Subcutaneously (SC) at Weeks 0, 2, 4, 6, 8, and 10. From Week 12 Placebo-treated participants who are in clinical response at Week 12 (>=100-point reduction from baseline in Crohn's Disease Activity Index (CDAI) or CDAI <150) will continue to receive placebo SC injections every 2 weeks from Week 12 through Week 22. Placebo -treated participants who are not in clinical response at Week 12 will receive JNJ-64304500 400 mg SC at Week 12 and then JNJ-64304500 200 mg every two weeks from Week 14 through Week 22. | Drug: JNJ-64304500<br>* Participants will receive JNJ-64304500 Subcutaneously.<br>Drug: Placebo<br>* Participants will receive placebo Subcutaneously.<br>|
| Experimental: Part I : JNJ-64304500<br>Participants will receive JNJ-64304500 400 milligram (mg) SC at Week 0 then 200 mg SC every two weeks through Week 22. | Drug: JNJ-64304500<br>* Participants will receive JNJ-64304500 Subcutaneously.<br>|
| Experimental: Part II : Placebo<br>Placebo SC at Weeks 0, 2, 4, and 8. From Week 12, placebo-treated participants who are in clinical response at Week 12 (>=100-point reduction from baseline in CDAI or CDAI <150) will continue to receive placebo at Weeks 12, 14, 16, and 20. Placebo -treated participants who are not in clinical response at Week 12 will receive JNJ-64304500 150 mg SC at Week 12 and then JNJ-64304500 75 mg at Weeks 14, 16, and 20. Participants who complete Part II 24 weeks assessment and may benefit from continued treatment in the opinion of the investigator are eligible to enter the Part II LTE in which they will continue to receive placebo up to 52 weeks (for a total of up to 72 weeks of placebo in Part II). The study has been unblinded due to lack of sufficient efficacy of JNJ- 64304500. Participants receiving placebo during the LTE will stop receiving placebo. | Drug: JNJ-64304500<br>* Participants will receive JNJ-64304500 Subcutaneously.<br>Drug: Placebo<br>* Participants will receive placebo Subcutaneously.<br>|
| Experimental: Part II : JNJ-64304500 High Dose<br>JNJ-64304500 400 mg SC at Week 0 and 200 mg SC at Weeks 2, 4, 8, 12, 16, and 20. Participants who complete Part II 24 weeks assessment and may benefit from continued treatment in the opinion of the investigator are eligible to enter the Part II LTE in which they will continue to receive JNJ-64304500 high dose up to 52 weeks (for a total of up to 72 weeks of JNJ-64304500 in Part II). The study has been unblinded due to lack of sufficient efficacy of JNJ-64304500. Participants receiving JNJ-64304500 during the LTE will stop receiving study drug and will have a final safety follow-up visit 16 weeks after the last dose of study drug. | Drug: JNJ-64304500<br>* Participants will receive JNJ-64304500 Subcutaneously.<br>|
| Experimental: Part II : JNJ-64304500 Middle Dose<br>JNJ-64304500 150 mg SC at Week 0 and 75 mg SC at Weeks 2, 4, 8, 12, 16, and 20. Participants who complete Part II 24 weeks assessment and may benefit from continued treatment in the opinion of the investigator are eligible to enter the Part II LTE in which they will continue to receive JNJ-64304500 middle dose up to 52 weeks (for a total of up to 72 weeks of JNJ-64304500 in Part II). The study has been unblinded due to lack of sufficient efficacy of JNJ-64304500. Participants receiving JNJ-64304500 during the LTE will stop receiving study drug and will have a final safety follow-up visit 16 weeks after the last dose of study drug. | Drug: JNJ-64304500<br>* Participants will receive JNJ-64304500 Subcutaneously.<br>|
| Experimental: Part II : JNJ-64304500 Low Dose<br>JNJ-64304500 50 mg SC at Week 0 and 25 mg SC at Weeks 2, 4, 8, 12, 16, and 20. Participants who complete Part II 24 weeks assessment and may benefit from continued treatment in the opinion of the investigator are eligible to enter the Part II LTE in which they will continue to receive JNJ-64304500 low dose up to 52 weeks (for a total of up to 72 weeks of JNJ-64304500 in Part II). The study has been unblinded due to lack of sufficient efficacy of JNJ-64304500. Participants receiving JNJ-64304500 during the LTE will stop receiving study drug and will have a final safety follow-up visit 16 weeks after the last dose of study drug. | Drug: JNJ-64304500<br>* Participants will receive JNJ-64304500 Subcutaneously.<br>|
| Experimental: Part II : Ustekinumab<br>Participants will receive tiered doses of Ustekinumab 260 mg (weight <=55 kg), Ustekinumab 390 mg (weight >55 kg and <=85 kg), Ustekinumab 520 mg (weight >85 kg) intravenously at Week 0 followed by 90 mg subcutaneously at Weeks 8 and 16. Participants who complete Part II 24 weeks assessment and may benefit from continued treatment in the opinion of the investigator are eligible to enter the Part II LTE in which they will continue to receive Ustekinumab up to 52 weeks (for a total of up to 72 weeks of Ustekinumab in Part II). The study has been unblinded due to lack of sufficient efficacy of JNJ-64304500. Participants receiving Ustekinumab during the LTE will stop receiving study drug and will have a final safety follow-up visit after the last dose of study drug. However, participants receiving Ustekinumab in countries where Ustekinumab is not commercially available or approved for adult Crohn's disease were continued to receive Ustekinumab in the LTE. | Drug: Ustekinumab<br>* Participants will receive ustekinumab as per the dosing regimen.<br>* Other names: STELARA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part I: Change From Baseline in the Crohn's Disease Activity Index (CDAI) Score at Week 8 | 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. The CDAI score was assessed by collecting information on 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 4 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. | Baseline to Week 8 | 
| Part II: Change From Baseline in the CDAI Score at Week 12 | 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. The CDAI was assessed by collecting information on 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 4 variables are 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. | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part II: Percentage of Participants in Clinical Remission at Week 12 as Measured by CDAI (CDAI Less Than [<] 150) | Clinical Remission was defined as a CDAI score of <150 point. The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. 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. A decrease in CDAI over time indicates improvement in disease activity. In general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. | Week 12 | 
| Part II: Percentage of Participants in Clinical Response at Week 12 as Measured by CDAI (Greater Than or Equal to [>=] 100-point Reduction From Baseline in CDAI or CDAI <150) | Clinical response was defined as a >=100-point reduction from the baseline CDAI score, or a CDAI score <150. The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. 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 CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity. In general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. | Week 12 | 
| Part II: Change From Baseline in Patient-Reported Outcome (PRO)-2 at Week 12 | The PRO-2 score is defined as the sum of the abdominal pain and stool frequency components of the CDAI. PRO-2 scores ranges from 0 to approximately 300, higher score indicates higher disease activity. | Baseline, Week 12 | 
| Part II: Percentage of Participants in Clinical Remission at Week 12 as Measured by PRO-2 (PRO-2 <75) | Clinical Remission was defined as a PRO-2 score of <75 point. | Week 12 | 
| Part II: Percentage of Participants in Clinical Response at Week 12 as Measured by PRO-2 (>=50-point Reduction From Baseline in PRO-2 Score or PRO-2 Score <75) | Clinical response was defined as >=50-point reduction from baseline in PRO-2 or Score or PRO-2 Score <75. | Week 12 | 
| Part II: Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12 | SES-CD is a validated instrument reflecting an endoscopist global appraisal of mucosal lesions in Crohn's disease. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. The total SES-CD was calculated as the sum of the 4 variables for the 5 bowel segments: rectum, left colon, transverse colon, right colon, and ileum. Scores range from 0 to 60, with higher scores indicating more severe disease. | Baseline, Week 12 |