A Study of Guselkumab in Participants With Moderate to Severe Plaque-type Psoriasis and an Inadequate Response to Ustekinumab

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of guselkumab (CNTO 1959) in the treatment of participants with moderate to severe plaque-type psoriasis (scaly skin rash) who had inadequate response to ustekinumab.

Detailed Description
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This is a randomized (assignment of study drug by chance), double-blind (participants nor study staff will know the identity of study drugs), multicenter study to evaluate efficacy and safety of guselkumab for the treatment of participants with moderate to severe plaque-type psoriasis who had an inadequate response to ustekinumab. The study will consist of a screening period, open-label and double-blind treatment periods, and a follow-up period. The treatment period will have 2 phases: an open-label treatment phase during which all participants will receive ustekinumab at Weeks 0 and 4 and a blinded treatment phase during which participants with an inadequate Investigator's Global Assessment response (IGA≥2) to ustekinumab at Week 16 will be randomized to receive either guselkumab or ustekinumab through Week 44. Participants with an IGA response of 0 or 1 (cleared or minimal disease) at Week 16 will continue to receive open-label treatment with ustekinumab every 12 weeks through Week 40. All participants will complete a follow-up phase through Week 52 for efficacy and through Week 60 for safety evaluations. The total duration of the study will be approximately 64 weeks (includes a 4-week screening period). Participants' safety will be monitored throughout the study.

Official Title
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A Phase 3, Multicenter, Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Guselkumab for the Treatment of Subjects With Moderate to Severe Plaque-type Psoriasis and an Inadequate Response to Ustekinumab

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Ustekinumab
* Drug: Guselkumab
* Drug: Placebo for ustekinumab
* Drug: Placebo for guselkumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of plaque-type psoriasis (with or without psoriatic arthritis for at least 6 months before the first administration of study drug Have a Psoriasis Area and Severity Index (PASI) greater than or equal to (>=) 12 at Screening and at Baseline Have an Investigator's Global Assessment (IGA) >=3 at Screening and at Baseline Have an involved body surface area (BSA) >= 10 percent (%) at Screening and at Baseline Be a candidate for phototherapy or systemic treatment for psoriasis (either naïve or history of previous treatment) Exclusion Criteria: Has a history or current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances Has unstable cardiovascular disease, defined as a recent clinical deterioration (example [eg], unstable angina, rapid atrial fibrillation) in the last 3 months or a cardiac hospitalization within the last 3 months Currently has a malignancy or has a history of malignancy within 5 years before Screening (with the exception of a nonmelanoma skin cancer that has been adequately treated with no evidence of recurrence for at least 3 months before the first study drug administration, or cervical carcinoma in situ that has been treated with no evidence of recurrence for at least 3 months before the first study drug administration) Has previously received guselkumab or ustekinumab

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-label ustekinumab<br> | Drug: Ustekinumab<br>* 45 mg or 90 mg given by subcutaneous injection at Weeks 0 and 4 for all participants. Participants with an IGA score of 0 or 1 at Week 16 will also receive ustekinumab every 12 weeks (q12w) from Week 16 to Week 40.<br>|
| Experimental: Double-blind guselkumab<br> | Drug: Guselkumab<br>* 100 mg given by subcutaneous injection at Weeks 16 and 20 and every 8 weeks (q8w) thereafter through Week 44.<br>Drug: Placebo for ustekinumab<br>* Subcutaneous injection at Weeks 16, 28, and 40 to maintain the blind for participants randomized to treatment with guselkumab.<br>|
| Experimental: Double-blind ustekinumab<br> | Drug: Ustekinumab<br>* 45 mg or 90 mg given by subcutaneous injection at Weeks 0 and 4 for all participants. Participants with an IGA score of 0 or 1 at Week 16 will also receive ustekinumab every 12 weeks (q12w) from Week 16 to Week 40.<br>Drug: Placebo for guselkumab<br>* Subcutaneous injection at Weeks 16 and 20 and q8w thereafter through Week 44 to maintain the blind for participants randomized to treatment with ustekinumab.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Visits at Which Participants Achieved an Investigator's Global Assessment (IGA) Response of Cleared (0) or Minimal (1) and at Least a 2 Grade Improvement (From Week 16) From Week 28 Through Week 40 | The IGA documents the investigator's assessment of the participants psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The participants' psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). | Week 28 through Week 40 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Visits at Which Participants Achieved a Psoriasis Area and Severity Index (PASI) 90 Response From Week 28 Through Week 40 | The PASI is a system used for assessing and grading the severity of psoriatic lesions. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 90 response represents participants who achieved at least a 90 percent improvement from baseline in the PASI score. | Week 28 through Week 40 | 
| Number of Visits at Which Participants Achieved an IGA Score of Cleared (0) From Week 28 Through Week 40 | The IGA documents the investigator's assessment of the participants psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The participants' psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). | Week 28 through Week 40 | 
| Percentage of Participants With an Investigator's Global Assessment (IGA) Score of Cleared (0) or Minimal (1) and at Least a 2 Grade Improvement (From Week 16) at Week 28 | The IGA documents the investigator's assessment of the participants psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The participants' psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). | Week 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis, Plaque-type psoriasis, Guselkumab, Ustekinumab, CNTO 1959, Monoclonal antibody