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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 2

Conditions: Crohn Disease

Treatments: Drug: Ustekinumab; Drug: Placebo; Drug: JNJ-64304500

Study type: Interventional

Funder types: Industry

Identifiers

NCT02877134

64304500CRD2001 (Other Identifier)

2016-000634-21 (EudraCT Number)

CR108136

Details and patient eligibility

About

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.

Enrollment: 388 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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388 participants in 7 patient groups

Part I : Placebo

Experimental group

Description:

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.

Treatment:

Drug: JNJ-64304500

Drug: Placebo

Part I : JNJ-64304500

Experimental group

Description:

Participants will receive JNJ-64304500 400 milligram (mg) SC at Week 0 then 200 mg SC every two weeks through Week 22.

Treatment:

Drug: JNJ-64304500

Part II : Placebo

Experimental group

Description:

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.

Treatment:

Drug: JNJ-64304500

Drug: Placebo

Part II : JNJ-64304500 High Dose

Experimental group

Description:

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.

Treatment:

Drug: JNJ-64304500

Part II : JNJ-64304500 Middle Dose

Experimental group

Description:

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.

Treatment:

Drug: JNJ-64304500

Part II : JNJ-64304500 Low Dose

Experimental group

Description:

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.

Treatment:

Drug: JNJ-64304500

Part II : Ustekinumab

Experimental group

Description:

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.

Treatment:

Drug: Ustekinumab