A Study of Ustekinumab to Evaluate a Subject-tailored Maintenance Dosing Approach in Subjects With Moderate-to-Severe Plaque Psoriasis

Study Overview
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Brief Summary
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The purpose of the study is to assess the effect of extending maintenance dosing intervals beyond 12 weeks on the clinical efficacy and safety of ustekinumab in subjects with moderate-to-severe plaque psoriasis.

Detailed Description
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In this study, a proportion of subjects will receive study agent at its recommended dose and interval (45mg for subjects less than or equal to 100kg, or 90mg for subjects greater than 100kg; every 12 weeks after 2 starter doses at Weeks 0 and 4). The majority of subjects will have the opportunity to receive study agent less frequently during the randomization period depending on the subject's response. The study consists of a 4-week screening period; a 28-week open-label run-in period; a double-blind treatment period from Week 28 to Week 104; a 12 week post-treatment period; and a 20-week safety follow-up. Participants will be randomized for the double blind period into one of two study groups. Group 1 participants will receive an injection of the study medication at a 12 week dosing interval. Group 2 participants will undergo a placebo withdrawal and may receive study agents at an extended interval greater than 12 weeks. During the double-blind treatment period, subjects in Groups 1 and 2 will receive placebo as necessary to maintain the blind.

Official Title
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A Phase 3b, Randomized, Double-blind, Active-controlled, Multicenter Study to Evaluate a Subject-tailored Maintenance Dosing Approach in Subjects With Moderate-to-Severe Plaque Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Ustekinumab 45 mg
* Drug: Ustekinumab 90 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Eligibility Criteria Male or female Have had a diagnosis of plaque-type psoriasis at least 6 months prior to the first administration of study agent (subjects with concurrent psoriatic arthritis may be enrolled). Have plaque-type psoriasis covering at least 10% of their total BSA at screening and at the time of the first administration of study agent. Have a PGA score of ≥ 3 at screening and at the time of the first administration of study agent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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 |
| --- | --- |
| Experimental: Group 1: Approved q12w maintenance regimen<br>Active ustekinumab study agent q12 weeks with sham/placebo as necessary to maintain blind | Drug: Ustekinumab 45 mg<br>* Form = Injection, route = subcutaneous<br>Drug: Ustekinumab 90 mg<br>* Form = Injection, route = subcutaneous<br>Drug: Placebo<br>* Form = Injection, route = subcutaneous<br>|
| Experimental: Group 2: Subject-tailored fixed-interval maintenance regimen<br>Subjects will undergo placebo withdrawal and will receive active study agent up to q24w intervals with sham/placebo injections to maintain the blind. | Drug: Ustekinumab 45 mg<br>* Form = Injection, route = subcutaneous<br>Drug: Ustekinumab 90 mg<br>* Form = Injection, route = subcutaneous<br>Drug: Placebo<br>* Form = Injection, route = subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Visits at Which Participants Achieved a Static Physician Global Assessment (PGA) Score of Cleared (0) or Minimal (1) | Clinical responses for week (wk)28 sPGA responders randomized to every 12 weeks (q12wk) fixed-interval dosing (Group 1) vs. patient-tailored fixed-interval dosing (Group 2) were assessed using the static PGA (sPGA) measure. Investigators graded psoriasis lesions for induration (0=no plaque elevation to 5=severe plaque elevation), erythema (0=no evidence of erythema to 5=dusky to deep red coloration), and scaling (0=no evidence of scaling to 5=severe scaling). The sum of the 3 scales is divided by 3 and rounded to obtain a final sPGA score, defined as 0=cleared (except for residual discoloration), 1=minimal, 2=mild, 3=moderate, 4=marked or 5=severe. | Up to 24 weeks (Week 88 up to Week 112 [total 7 visits]) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants With a Static PGA Score of Cleared (0) or Minimal (1) Over Time | Clinical responses for week (wk) 28 sPGA responders randomized to every 12 weeks (q12wk) fixed-interval dosing (Group 1) vs. patient-tailored fixed-interval dosing (Group 2) were assessed using the static PGA (sPGA) measure. Investigators graded psoriasis lesions for induration (0=no plaque elevation to 5=severe plaque elevation), erythema (0=no evidence of erythema to 5=dusky to deep red coloration), and scaling (0=no evidence of scaling to 5=severe scaling). The sum of the 3 scales is divided by 3 and rounded to obtain a final sPGA score, defined as 0=cleared (except for residual discoloration), 1=minimal, 2=mild, 3=moderate, 4=marked or 5=severe. | Week 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, 112 | 
| The Number of Visits for Which Participants Achieved a Psoriasis Area and Severity Index (PASI) 75 Response | The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. The PASI produces a numeric score that can range from 0 to 72. A PASI 75 response is defined as greater than or equal to (>=) 75 percent (%) improvement in PASI score from baseline. | Up to 24 weeks (Week 88 up to Week 112 [total 7 visits]) | 
| The Percentage of Participants With a PASI 75 Response Over Time | The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. The PASI produces a numeric score that can range from 0 to 72. A PASI 75 response is defined as greater than or equal to (>=) 75 percent (%) improvement in PASI score from baseline. | Week 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, 112 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis, Ustekinumab, STELARA, Skin disease, Monoclonal