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

Study Overview
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Brief Summary
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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
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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).

Official Title
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A Phase 2b, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Dose-response Study Evaluating the Efficacy and Safety of JNJ-54781532 in Subjects With Moderately to Severely Active Ulcerative Colitis

Conditions
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Colitis, Ulcerative

Intervention / Treatment
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* Drug: Placebo
* Drug: JNJ-54781532 25 mg once daily
* Drug: JNJ-54781532 75 mg once daily
* Drug: JNJ-54781532 150 mg once daily
* Drug: JNJ-54781532 75 mg twice daily


Participation Criteria
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Eligibility Criteria
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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)

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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 | Drug: Placebo<br>* Participants will receive placebo once daily<br>Drug: JNJ-54781532 150 mg once daily<br>* Participants will receive 150 mg of JNJ-54781532 once daily<br>* Other names: ASP015K;|
| Experimental: JNJ-54781532 25 mg once daily<br>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 | Drug: JNJ-54781532 25 mg once daily<br>* Participants will receive 25 mg of JNJ-54781532 once daily<br>* Other names: ASP015K;|
| Experimental: JNJ-54781532 75 mg once daily<br>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 | Drug: JNJ-54781532 75 mg once daily<br>* Participants will receive 75 mg of JNJ-54781532 once daily<br>* Other names: ASP015K;|
| Experimental: JNJ-54781532 150 mg once daily<br>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 | Drug: JNJ-54781532 150 mg once daily<br>* Participants will receive 150 mg of JNJ-54781532 once daily<br>* Other names: ASP015K;|
| Experimental: JNJ-54781532 75 mg twice daily<br>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 | Drug: JNJ-54781532 75 mg twice daily<br>* Participants will receive 75 mg of JNJ-54781532 twice daily<br>* Other names: ASP015K;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the Mayo score at 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. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with clinical response at 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. | Week 8 | 
| Number of participants with clinical remission at Week 8 | Clinical remission is defined as a Mayo score ≤2 points, with no individual subscore >1. | Week 8 | 
| Number of participants with mucosal healing at 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. | Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colitis, Ulcerative, JNJ-54781532, Moderate, Severe, Active