Colitis, Ulcerative
Conditions
Keywords
Colitis, Ulcerative, JNJ-54781532, Moderate, Severe, Active
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).
Interventions
DRUGPlacebo
Participants will receive placebo once daily
DRUGJNJ-54781532 25 mg once daily
Participants will receive 25 mg of JNJ-54781532 once daily
DRUGJNJ-54781532 75 mg once daily
Participants will receive 75 mg of JNJ-54781532 once daily
DRUGJNJ-54781532 150 mg once daily
Participants will receive 150 mg of JNJ-54781532 once daily
DRUGJNJ-54781532 75 mg twice daily
Participants will receive 75 mg of JNJ-54781532 twice daily
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
Australia, Belgium, Bulgaria, Canada, France, Germany, Hungary, Israel, Netherlands, Poland, Romania, Russia, Ukraine, United States
Outcome results
None listed