A Study of Safety and Effectiveness of JNJ-54781532 in Patients With Moderately to Severely Active Ulcerative Colitis

Phase 2

Completed

• Conditions: Colitis, Ulcerative
• Interventions: Drug: Placebo; Drug: JNJ-54781532 25 mg once daily; Drug: JNJ-54781532 75 mg twice daily; Drug: JNJ-54781532 75 mg once daily; Drug: JNJ-54781532 150 mg once daily

• Registration Number: NCT01959282
• Lead Sponsor: Janssen Research & Development, LLC

Brief Summary

The purpose of the study is to evaluate dose response of JNJ-54781532 in participants with moderately to severely active ulcerative colitis (UC).

Detailed Description

This is a Phase 2b, multicenter, randomized (the study medication is assigned by chance), double-blind (neither physician nor participant knows the treatment that the participant receives), placebo-controlled (an inactive substance that is compared with a medication to test whether the medication has a real effect in a clinical study), parallel-group (each group of participants will be treated at the same time), dose-response study (a study to evaluate response to different dosages of study medication) of oral tablets of JNJ-54781532 in adult participants with moderately to severely active UC. Approximately 220 participants will be randomized in a 1:1:1:1:1 ratio to 1 of 5 treatment groups at Week 0 (placebo; JNJ-54781532 25 mg once daily; JNJ-54781532 75 mg once daily; JNJ-54781532 150 mg once daily; and JNJ-54781532 75 mg twice daily) to receive their randomized dosage of study medication through Week 8 and will be assessed for clinical response at Week 8. Participants who achieve clinical response at Week 8 will continue to receive their original randomized dosage of study medication through Week 32. Participants who do not achieve clinical response at Week 8 will be treated as follows: participants originally randomized to placebo will receive JNJ-54781532 150 mg once daily through Week 16; participants originally randomized to JNJ-54781532 will continue to receive their original randomized dosage of JNJ-54781532 through Week 16. Participants who were not in clinical response at Week 8 and do not achieve a partial Mayo score response (a decrease from baseline in the partial Mayo score by ≥3 points) at Week 16 will be discontinued from study medication; and those who achieve a partial Mayo score response at Week 16 can continue receiving JNJ 54781532 through Week 32. Participants will be evaluated for safety (adverse events) up to Week 36 (ie, 4 weeks after the last dose of study medication). The maximum study duration for each participant will be approximately 44 weeks (including maximum screening period).

Study Timeline

• Study First Submitted: 2013-10-07
• Study First Submitted QC: 2013-10-07
• Study First Posted: 2013-10-10
• Study Start: 2013-11-15
• Primary Completion: 2015-05-20
• Study Completion: 2015-12-05
• Disposition First Submitted: 2016-04-14
• Disposition First Submitted QC: 2016-04-14
• Disposition First Posted: 2016-05-16
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-03
• Last Update Posted: 2019-01-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 219

Inclusion Criteria

• Have a clinical diagnosis of ulcerative colitis (UC) at least 3 months prior to screening
• Have moderately to severely active UC, defined as a baseline (Week 0) Mayo score of 6 to 12; including an endoscopy sub score greater than or equal to 2 as determined by a central read of the video endoscopy
• Current treatment with oral corticosteroids or have a history of failure to respond to, or tolerate, at least 1 of the following therapies oral corticosteroids (including budesonide), 6-mercaptopurine (6-MP), azathioprine (AZA), or anti- tumor necrosis factor therapy or be corticosteroid dependent (ie, an inability to successfully taper corticosteroids without a return of the symptoms of UC)
• Must discontinue 6-MP/AZA for at least 1 week before the first dose of study medication

Exclusion Criteria

• At imminent risk for colectomy
• Have ulcerative colitis limited to the rectum only or to less than 20 centimeter of the colon
• Presence of a stoma
• Presence or history of a fistula
• History or current diagnosis of active or latent tuberculosis; human immunodeficiency virus; hepatitis C virus or hepatitis B virus infection; have had more than 1 herpes zoster infection or have had any diagnosis of disseminated herpes zoster
• Previous treatment with a janus kinase inhibitor (eg, tofacitinib)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants will receive placebo once daily from Week 0 to Week 8. Participants in clinical response at Week 8 will continue to receive placebo through Week 32. Participants not in clinical response at Week 8 will receive treatment with 150 mg JNJ-54781532 orally once daily from Week 8 to Week 16. Participants who achieve a partial Mayo score response (ie, a change from baseline of ≥3 in the partial Mayo score) at Week 16 can continue receiving 150 mg JNJ-54781532 orally once daily through Week 32
Placebo	JNJ-54781532 150 mg once daily	Participants will receive placebo once daily from Week 0 to Week 8. Participants in clinical response at Week 8 will continue to receive placebo through Week 32. Participants not in clinical response at Week 8 will receive treatment with 150 mg JNJ-54781532 orally once daily from Week 8 to Week 16. Participants who achieve a partial Mayo score response (ie, a change from baseline of ≥3 in the partial Mayo score) at Week 16 can continue receiving 150 mg JNJ-54781532 orally once daily through Week 32
JNJ-54781532 25 mg once daily	JNJ-54781532 25 mg once daily	Participants will receive 25 mg of JNJ-54781532 once daily from Week 0 to Week 8. Participants in clinical response at Week 8 will continue to receive the same dosage through Week 32 and participants not in clinical response at Week 8 will continue to receive the same dosage through Week 16. At Week 16, participants who do not achieve a partial Mayo score response (ie, a change from baseline of ≥3 in the partial Mayo score) will be discontinued from study medication, and participants who achieve a partial Mayo score response at Week 16 can continue receiving JNJ 54781532 25 mg once daily through Week 32
JNJ-54781532 75 mg twice daily	JNJ-54781532 75 mg twice daily	Participants will receive 75 mg of JNJ-54781532 twice daily from Week 0 to Week 8. Participants in clinical response at Week 8 will continue to receive the same dosage through Week 32 and participants not in clinical response at Week 8 will continue to receive the same dosage through Week 16. At Week 16, participants who do not achieve a partial Mayo score response (ie, a change from baseline of ≥3 in the partial Mayo score) will be discontinued from study medication, and participants who achieve a partial Mayo score response at Week 16 can continue receiving JNJ 54781532 75 mg twice daily through Week 32
JNJ-54781532 75 mg once daily	JNJ-54781532 75 mg once daily	Participants will receive 75 mg of JNJ-54781532 once daily from Week 0 to Week 8. Participants in clinical response at Week 8 will continue to receive the same dosage through Week 32 and participants not in clinical response at Week 8 will continue to receive the same dosage through Week 16. At Week 16, participants who do not achieve a partial Mayo score response (ie, a change from baseline of ≥3 in the partial Mayo score) will be discontinued from study medication, and participants who achieve a partial Mayo score response at Week 16 can continue receiving JNJ 54781532 75 mg once daily through Week 32
JNJ-54781532 150 mg once daily	JNJ-54781532 150 mg once daily	Participants will receive 150 mg of JNJ-54781532 once daily from Week 0 to Week 8. Participants in clinical response at Week 8 will continue to receive the same dosage through Week 32 and participants not in clinical response at Week 8 will continue to receive the same dosage through Week 16. At Week 16, participants who do not achieve a partial Mayo score response (ie, a change from baseline of ≥3 in the partial Mayo score) will be discontinued from study medication, and participants who achieve a partial Mayo score response at Week 16 can continue receiving JNJ 54781532 150 mg once daily through Week 32

Primary Outcome Measures

Name	Time	Method
Change from baseline in the Mayo score at Week 8	Week 8	The Mayo score is the primary tool for assessing ulcerative colitis activity. The Mayo score consists of 4 subscores (stool frequency, rectal bleeding, findings of endoscopy, and physician's global assessment) which range from 0 to 3. The Mayo score is calculated as the sum of these 4 subscores and can range between 0 and 12. A score of 3 to 5 points indicates mildly active disease; a score of 6 to 10 indicates moderately active disease; and a score of 11 to 12 indicates severe disease.

Secondary Outcome Measures

Name	Time	Method
Number of participants with clinical remission at Week 8	Week 8	Clinical remission is defined as a Mayo score ≤2 points, with no individual subscore \>1.
Number of participants with mucosal healing at Week 8	Week 8	Mucosal healing is an improvement in the endoscopic appearance of the mucosa. An endoscopy subscore of the Mayo score of 0 or 1.
Number of participants with clinical response at Week 8	Week 8	Clinical response is defined as a decrease from baseline in the Mayo score by ≥30% and ≥3 points, with either a decrease from baseline in the rectal bleeding subscore of ≥1 or a rectal bleeding subscore of 0 or 1.