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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 2

Conditions: Colitis, Ulcerative

Treatments: Drug: Placebo; Drug: JNJ-54781532 25 mg once daily; Drug: JNJ-54781532 75 mg twice daily; Drug: JNJ-54781532 150 mg once daily; Drug: JNJ-54781532 75 mg once daily

Study type: Interventional

Funder types: Industry

Identifiers

NCT01959282

CR102640

54781532UCO2001 (Other Identifier)

2013-000263-88 (EudraCT Number)

Details and patient eligibility

About

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

Full 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).

Enrollment: 219 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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219 participants in 5 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: JNJ-54781532 150 mg once daily

Drug: Placebo

JNJ-54781532 25 mg once daily

Experimental group

Description:

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

Treatment:

Drug: JNJ-54781532 25 mg once daily

JNJ-54781532 75 mg once daily

Experimental group

Description:

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

Treatment:

Drug: JNJ-54781532 75 mg once daily

JNJ-54781532 150 mg once daily

Experimental group

Description:

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

Treatment:

Drug: JNJ-54781532 150 mg once daily

JNJ-54781532 75 mg twice daily

Experimental group

Description:

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

Treatment:

Drug: JNJ-54781532 75 mg twice daily