A Study of Safety and Effectiveness of Ustekinumab (CNTO 1275) in Patients With Moderate to Severe Plaque-type Psoriasis

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

Detailed Description
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This is a randomized (patients are assigned to different treatments based on chance), double blind (neither the patient nor the physician knows whether medication or placebo [an inactive substance that is compared with a medication to test whether the medication has a real effect in a clinical study] is being taken, or at what dosage), parallel-group (each group of patients are treated at the same time), multicenter study to determine the effectiveness and safety of two different doses of ustekinumab administered subcutaneously (under the skin) as compared with placebo in patients with moderate to severe plaque-type psoriasis (the most common type of psoriasis). 766 patients will be randomized to Group 1 (ustekinumab 45 mg), Group 2 (ustekinumab 90 mg) and Group 3 (placebo) at Week 0. The study was designed to evaluate the effectiveness and safety of 2 dose regimens of ustekinumab: (1) 45 mg at Weeks 0 and 4 followed by 45 mg every 12 weeks maintenance therapy (treatment designed to help the original primary treatment succeed) and (2) 90 mg at Weeks 0 and 4 followed by 90 mg every 12 weeks maintenance therapy. The study will consist of 4 periods: (1) Placebo-controlled portion of study [Week 0 to Week 12] during which the safety and effectiveness of 2 doses (45mg and 90mg) of ustekinumab will be compared to placebo; (2) Placebo crossover and active treatment portion of study [Week 12 to Week 40] during which patients randomized to receive placebo at Week 0 will crossover to receive ustekinumab, and all patients will receive active treatment; (3) Randomized withdrawal portion of study [beginning at Week 40] during which patients who received ustekinumab [45mg or 90mg every 12 weeks] at Week 0 and are responding to it, will be randomized either to placebo or continued maintenance therapy with ustekinumab; and (4) Long-term extension [from Week 52 to Week 264 (ie, 5 years)] period during which the safety and effectiveness of ustekinumab long-term use will be evaluated in patients.

Official Title
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A Phase 3, Multicenter, Randomized, Double-blind, Placebo Controlled Trial Evaluating the Efficacy and Safety of Ustekinumab (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: ustekinumab
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with plaque-type psoriasis diagnosed at least 6 months prior and covering at least 10% of total body surface areas Have psoriasis area-and-severity index score of >=12 Patients who are considered by treating dermatologist to be a candidate for phototherapy or systemic treatment of psoriasis Have no history of latent or active TB Exclusion Criteria: Currently have nonplaque forms of psoriasis or drug-induced psoriasis Have any therapeutic agent targeted at reducing IL-12 or IL-23 Have had a BCG vaccination within the previous 12 months 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 Have or ever have had a nontuberculous mycobacterial infection or opportunistic infection Patients known to be infected with human immunodeficiency virus, hepatitis B, or hepatitis C 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)

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ustekinumab 45 mg<br>Patients received ustekinumab 45 mg at Weeks 0, 4 and 16. Treatments after Week 16 were dependent on clinical response. At Week 40, patients who achieved PASI 75 at both Week 28 and Week 40 were re-randomized to withdraw from therapy (placebo) or continue 45 mg every 12 week maintenance therapy. | Drug: ustekinumab<br>* Type = exact number, Form = solution for injection, Number = 45 and 90, Unit = mg, Route = subcutaneous (SC) administered at Weeks 0, 4 and 16. Both treatments (45 mg and 90 mg) administered every 12 weeks after Week 16 depending on clinical response.<br>* Other names: CNTO 1275;|
| Experimental: ustekinumab 90 mg<br>Patients received ustekinumab 90 mg at Week 0, 4 and 16. Treatments after Week 16 were dependent on clinical response. At Week 40, patients who achieved PASI 75 at both Week 28 and Week 40 were re-randomized to withdraw from therapy (placebo) or continue 90 mg every 12 week maintenance therapy. | Drug: ustekinumab<br>* Type = exact number, Form = solution for injection, Number = 45 and 90, Unit = mg, Route = subcutaneous (SC) administered at Weeks 0, 4 and 16. Both treatments (45 mg and 90 mg) administered every 12 weeks after Week 16 depending on clinical response.<br>* Other names: CNTO 1275;|
| Placebo Comparator: Placebo<br>Patients received placebo at Weeks 0 and 4. At Weeks 12 and 16, placebo crossed over to receive ustekinumab 45 mg or 90 mg. Treatments after Week 16 were dependent on clinical response. | Drug: placebo<br>* Form = solution for injection, route = SC administered at Weeks 0 and 4. At Weeks 12 and 16, placebo will be crossed over to receive ustekinumab 45 mg or 90 mg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psoriasis Area-and-severity Index (PASI) 75% Improvement From Baseline at Week 12. | The number of participants achieving at least 75% improvement from baseline in Psoriasis Area and Severity Index (PASI) (0 [best] - 72 [worst]) at Week 12. This is a test of how bad a person's psoriasis is. The combination of redness, scaling, and thickness, as well as overall body involvement determine the PASI score. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieved a Physician Global Assessment (PGA) Score of Cleared (0) or Minimal (1) at Week 12 | The PGA is used to determine the participant's psoriasis lesions overall at a given time point. Overall lesions will be graded as : (0) = cleared, (1) = minimal, (2) = mild, (3) = moderate, (4) = marked, and (5) = severe for induration, erythema, and scaling. The sum of the 3 scales will be divided by 3 to obtain a final PGA score ranging from 0 [best] to 5 [worst]. | Week 12 | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 12 | Change from baseline in Dermatology Life Quality Index (DLQI) from baseline at Week 12. This 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 (Week 0), Week 12 | 
| Psoriasis Area and Severity Index (PASI) 75 Responders at Week 52 | The number of participants achieving at least 75% improvement from baseline in Psoriasis Area and Severity Index (PASI) (0 [best] - 72 [worst]) at Week 52 in participants randomly assigned to a treatment group at Week 40. This is a test of how bad a person's psoriasis is. The combination of redness, scaling, and thickness, as well as overall body involvement determine the PASI score. | Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ustekinumab, CNTO1275, Plaque type Psoriasis, Interleukin-23, IL-23, Psoriasis, Interleukin 12, IL-12