A Study of the Safety and Efficacy of Ustekinumab (CNTO 1275) in Patients With Moderate to Severe Psoriasis

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the efficacy and safety of ustekinumab (CNTO 1275) in the treatment of patients with moderate to severe plaque psoriasis.

Detailed Description
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Although numerous therapeutic options exist for the treatment of psoriasis, there is still a significant unmet medical need due to the limited effectiveness and/or significant side effect profile of current treatment options. Preclinical studies and early phase clinical studies suggest that interleukins-12 and -23, two molecules that are part of the communication network in the immune system, may play an important role in psoriasis. Ustekinumab (CNTO 1275) is a monoclonal antibody directed against interleukins -12 and -23. This is a randomized (study drug assigned by chance like flipping a coin), double blind (neither physician nor patient knows the name of the assigned drug), parallel-group, multicenter study to determine the effectiveness and safety of two different doses of ustekinumab (CNTO 1275) administered subcutaneously (under the skin) as compared with placebo in patients with moderate to severe plaque-type psoriasis (the most common type of psoriasis). The hypothesis is that ustekinumab (CNTO 1275) will be more effective in treatment of psoriasis than placebo, that the improvement in psoriasis will result in an improved quality of life for treated patients and that ustekinumab (CNTO 1275) will be generally well tolerated. Patients will receive ustekinumab (CNTO 1275), 45 or 90 mg, or placebo administered subcutaneously at weeks 0 and 4 weeks then every 12 weeks thereafter until week 52. For patients who partially respond to the starting regimen, the dosing interval may be adjusted to every 8 weeks. Patients will enter long term extension portion of the study at week 52 during which patients will continue to receive treatment with ustekinumab (CNTO 1275) and will be followed for a total of up to 264 weeks from the initial (week 0) administration of study agent. The dose of ustekinumab (CNTO 1275) will be 45 or 90 mg or placebo administered subcutaneously at weeks 0 and 4 weeks then every 12 weeks thereafter. For patients who partially respond to the starting regimen, the dosing interval may be adjusted to every 8 weeks.

Official Title
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A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial Evaluating the Efficacy and Safety of CNTO 1275 in the Treatment of Subjects With Moderate to Severe Plaque-type Psoriasis.

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Placebo; Ustekinumab (CNTO 1275) 45 or 90 mg
* Drug: Ustekinumab (CNTO 1275) 45 mg
* Drug: Ustekinumab (CNTO 1275) 90 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Plaque-type psoriasis diagnosed >= 6 months prior Plaque-type psoriasis covering at least 10% of total body surface areas Psoriasis area-and-severity index score of >=12 at screening and baseline Considered by treating dermatologist to be a candidate for phototherapy or systemic treatment of psoriasis Women of childbearing potential and all men must agree to use adequate birth control measures throughout the trials and for 12 months following the last injection of study agent Have no history of latent or active tuberculosis (TB) Exclusion Criteria: Currently have nonplaque forms of psoriasis or drug-induced psoriasis Women who are pregnant or nursing, or men and women planning pregnancy while enrolled in the study Patients who have used any therapeutic agent targeted at reducing IL-12 or IL-23 Patients who have had a Bacillus Calmette-Guerin (BCG) vaccination within the previous 12 months prior to screening Patients who have a history of chronic or recurrent infectious disease or who have or have had a serious infection requiring hospitalization or intravenous antibiotics within the previous 2 months prior to screening Patients who have or ever have had a nontuberculous mycobacterial infection or opportunistic infection Patients known to be infected with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C Patients who have current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease Patients with a malignancy or who have a history of malignancy (with the exception of certain skin cancers and pre-invasive cervical cancer) Patients participating in another trial using an investigational agent or procedure Systemic immunosuppressants within 4 weeks of the first administration of study agent

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group I: Placebo<br> | Drug: Placebo; Ustekinumab (CNTO 1275) 45 or 90 mg<br>* Placebo at Weeks 0 and 4 and blinded SC injections of ustekinumab, 45 or 90 mg, at Weeks 12 and 16; followed by a dosing regimen to be determined by patient's response status for Weeks 28 to 52; followed by unblinded dosing that may be adjusted at the investigator's discretion for Weeks 52 to 264<br>|
| Experimental: Group II: Ustekinumab 45 mg<br> | Drug: Ustekinumab (CNTO 1275) 45 mg<br>* Ustekinumab, 45 mg, at Weeks 0 and 4 and every 12 weeks for Weeks 16 to 28. Followed by a dosing regimen to be determined by patient's response status for Weeks 28 to 52; followed by unblinded dosing that may be adjusted at the investigator's discretion for Weeks 52 to 264<br>|
| Experimental: Group III: Ustekinumab 90 mg<br> | Drug: Ustekinumab (CNTO 1275) 90 mg<br>* Ustekinumab, 90 mg, at Weeks 0 and 4 and every 12 weeks for Weeks 16 to 28. Followed by a dosing regimen to be determined by patient's response status for Weeks 28 to 52; followed by unblinded dosing that may be adjusted at the investigator's discretion for Weeks 52 to 264<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Psoriasis Area and Severity Index (PASI) Score of 75 Percent or Above at Week 12 | Number of participants achieving greater than or equal to 75 percent improvement in PASI at Week 12. PASI is a widely used tool for the measurement of severity of psoriasis. This is a test of how bad a person's psoriasis is. The scale combines redness, scaling, and thickness, as well as overall body involvement to determine the PASI score. The scale ranges from 0 (best) to 72 (worst). | Week 0 to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Physician Global Assessment (PGA) of Cleared or Minimal at Week 12 | Number of participants achieving a physician global assessment (PGA) (0 [none] to 5 [severe]) of cleared or minimal at Week 12. The PGA is 7-point scale used in clinical trials of various diseases. In this the physician checks the state of the disease and gives them score from 0 (clear) to 5 (severe). | Week 12 | 
| Change in Dermatology Life Quality Index (DLQI) at Week 12 | Change in Dermatology Life Quality Index (DLQI) from baseline at Week 12. The DLQI is a 10-item questionnaire, that in addition to evaluating overall quality of life, can be used to assess 6 different aspects that may affect quality of life: symptoms and feelings, daily activities, leisure, work or school performance, personal relationships, and treatment. Scores range from 0 (no impairment in quality of life) to 30 (most impairment in quality of life). | Baseline to Week 12 | 
| Number of Participants Visits With Psoriasis Area and Severity Index (PASI) 75 From Week 40 Through Week 52 | Number of visits at which participants randomized at Week 28 achieved at least 75 percent improvement from baseline in PASI from Week 40 through Week 52 in participants randomized at Week 28. PASI is a widely used tool for the measurement of severity of psoriasis. This is a test of how bad a person's psoriasis is. The scale combines redness, scaling, and thickness, as well as overall body involvement to determine the PASI score. The scale ranges from 0 (best) to 72 (worst). | Week 40 to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Moderate to Severe Plaque-Type Psoriasis, interleukin 23, IL-12, interleukin-12, interleukin-23, CNTO1275, biologic, Psoriasis, CNTO 1275, IL23, interleukin 12, IL-23, IL12, ustekinumab