An Efficacy and Safety Study of Ustekinumab (CNTO 1275) in Participants With Plaque Psoriasis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of ustekinumab (CNTO 1275) compared with placebo in participants with moderate to severe plaque type psoriasis.

Detailed Description
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This is a multicenter (involving more than 1 study center), randomized (study medication assigned by chance), double-blind (neither the invesitigator nor the participant knows the identity of the study medication), placebo- controlled (1 of the study medications is inactive), parallel-group comparative study (different groups of participants will receive different treatments at the same time). The total duration of the study will be 78 weeks which will be comprised of: a screening period (6 weeks); an efficacy assessment period (64 weeks [with a total of 7 treatments at Weeks 0, 4, 12, 16, 28, 40, and 52]) and a follow-up assessment period (8 weeks). The efficacy assessment period will further include: a placebo-controlled treatment period (Weeks 0-12) and an active drug treatment period (Weeks 12-64). During the placebo-controlled treatment period, participants will receive ustekinumab (45 mg or 90 mg) subcutaneously (SC-into the muscles) or placebo SC. During the active drug treatment period, participants will continue treatment with 45 mg or 90 mg SC as assigned during the placebo-controlled treatment period; however, participants in the placebo group will be divided into 2 groups and will receive ustekinumab 45 mg (Placebo A) or 90 mg (Placebo B) SC. Efficacy will be evaluated primarily by analysis of psoriasis area and severity index (PASI) score. Participant safety will also be monitored.

Official Title
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A Placebo-Controlled Double-Blind Comparative Study of CNTO1275 in Patients With Plaque Type Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Placebo (CP)
* Drug: Ustekinumab 45 mg (CP)
* Drug: Ustekinumab 90 mg (CP)
* Drug: Placebo A (After CP)
* Drug: Placebo B (After CP)
* Drug: Ustekinumab 45 mg (After CP)
* Drug: Ustekinumab 90 mg (After CP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants diagnosed with psoriasis (psoriasis vulgaris and psoriatic arthritis) at least 6 months before registration Participants with plaque type psoriasis covering at least 10 percent of total body surface area at the time of informed consent and at registration Participants with a PASI score of greater than or equal to 12 at the time of informed consent and at registration Female participants of childbearing potential or males, whose partner can be pregnant, must agree that he/she will continuously take an appropriate contraceptive measure for 1 year from the day of informed consent to termination of the final investigational treatment; in the case of childbearing potential females, pregnancy test at screening must be negative Participants must agree not to receive Bacillus Calmette-Guérin (BCG) vaccination and live vaccine inoculation for 1 year after final treatment with the investigational product Exclusion Criteria: Participants with guttate psoriasis, erythrodermic psoriasis, or pustular psoriasis Participants with a medical history of tuberculosis infection or suspected tuberculosis infection Participants with present or past history of chronic or recurrent infection (e.g., chronic or recurrent urinary tract infection or respiratory infection) Participants with a current serious infection (e.g., sepsis, hepatitis, pneumonia, or pyelonephritis) or those who experienced a serious infection within the 2 month period before registration and including participants who received intravenous administration of antibiotics or antiviral agents within the 2 month period before registration Participants with a current or past history of malignant tumors (except for basal cell carcinoma, intraepidermal squamous cell carcinoma in the skin and uterine cervical squamous cell carcinoma, whose treatment was completed and no sign suggesting a recurrence has been observed, and squamous cell carcinoma in the skin whose treatment was completed and no sign suggesting a recurrence has been observed in the past 5 years)

Ages Eligible for Study
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Minimum Age: 20 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 |
| --- | --- |
| Placebo Comparator: Placebo (CP)<br>Placebo 0.5 ml and 1.0 ml will be administered subcutaneously (SC) on Weeks 0 and 4 respectively during the controlled period (Weeks 0-12). | Drug: Placebo (CP)<br>* Placebo 0.5 ml and 1.0 ml will be administered subcutaneously (SC) on Weeks 0 and 4 respectively during the controlled period (Weeks 0-12).<br>|
| Active Comparator: Ustekinumab 45 mg (CP)<br>Ustekinumab 45 mg (0.5 ml) and placebo (1.0 ml) will be administered SC on Weeks 0 and 4 during controlled period (Weeks 0-12). | Drug: Ustekinumab 45 mg (CP)<br>* Ustekinumab 45 mg (0.5 ml) and placebo (1.0 ml) will be administered SC on Weeks 0 and 4 during controlled period (Weeks 0-12).<br>|
| Active Comparator: Ustekinumab 90 mg (CP)<br>Ustekinumab 90 mg (1.0 ml) and placebo (0.5 ml) will be administered SC on Weeks 0 and 4 during controlled period (Weeks 0-12). | Drug: Ustekinumab 90 mg (CP)<br>* Ustekinumab 90 mg (1.0 ml) and placebo (0.5 ml) will be administered SC on Weeks 0 and 4 during controlled period (Weeks 0-12).<br>|
| Placebo Comparator: Placebo A (After CP)<br>After the controlled period (that is [i.e.], during the active drug treatment period [Weeks 12-64]), the placebo group will be randomized into 2 groups, including Placebo A, in which ustekinumab 45 mg (0.5 ml) and placebo (1.0 ml) will be administered SC at Weeks 12, 16, 28, 40, and 52. | Drug: Placebo A (After CP)<br>* After the controlled period (i.e., during the active drug treatment period [Weeks 12-64]), the placebo group will be randomized into 2 groups, including Placebo A, in which ustekinumab 45 mg (0.5 ml) and placebo (1.0 ml) will be administered SC at Weeks 12, 16, 28, 40, and 52.<br>|
| Placebo Comparator: Placebo B (After CP)<br>After the controlled period (i.e., during the active drug treatment period [Weeks 12-64]), the placebo group will be randomized into 2 groups, including Placebo B, in which ustekinumab 90 mg (1.0 ml) and placebo (0.5 ml) will be administered SC at Weeks 12, 16, 28, 40, and 52. | Drug: Placebo B (After CP)<br>* After the controlled period (i.e., during the active drug treatment period [Weeks 12-64]), the placebo group will be randomized into 2 groups, including Placebo B, in which ustekinumab 90 mg (1.0 ml) and placebo (0.5 ml) will be administered SC at Weeks 12, 16, 28, 40, and 52.<br>|
| Active Comparator: Ustekinumab 45 mg (After CP)<br>After the controlled period (i.e., during the active drug treatment period [Weeks 12-64]), participants in the ustekinumab 45 mg group will receive placebo (0.5 ml and 1.0 ml) SC at Week 12 followed by ustekinumab 45 mg (0.5 ml) and placebo (1.0 ml) SC at Weeks 16, 28, 40 and 52. | Drug: Ustekinumab 45 mg (After CP)<br>* After the controlled period (i.e., during the active drug treatment period [Weeks 12-64]), participants in the ustekinumab 45 mg group will receive placebo (0.5 ml and 1.0 ml) SC at Week 12 followed by ustekinumab 45 mg (0.5 ml) and placebo (1.0 ml) SC at Weeks 16, 28, 40 and 52.<br>|
| Active Comparator: Ustekinumab 90 mg (After CP)<br>After the controlled period (i.e., during the active drug treatment period [Weeks 12-64]), participants in the ustekinumab 90 mg group will receive placebo (0.5 ml and 1.0 ml) SC at Week 12 followed by ustekinumab 90 mg (1.0 ml) and placebo (0.5 ml) SC at Weeks 16, 28, 40 and 52. | Drug: Ustekinumab 90 mg (After CP)<br>* After the controlled period (i.e., during the active drug treatment period [Weeks 12-64]), participants in the ustekinumab 90 mg group will receive placebo (0.5 ml and 1.0 ml) SC at Week 12 followed by ustekinumab 90 mg (1.0 ml) and placebo (0.5 ml) SC at Weeks 16, 28, 40 and 52.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Greater Than or Equal to 75 Percent (%) Improvement in Psoriasis Area and Severity Index (PASI) Score | Percentage of participants with >=75% improvement in PASI score at Week 12 from Baseline was reported. PASI is a widely used tool for the measurement of severity of psoriasis. The combination of redness, scaling, and thickness, as well as overall body involvement determine the PASI score. The scale ranges from 0 (best) to 72 (worst). Baseline visit refers to Week 0. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 12 | The DLQI is a self-administered 10-item questionnaire that is used to assess 6 different aspects of 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). | Week 12 | 
| Psoriasis Area and Severity Index (PASI) Score | PASI is a widely used tool for the measurement of severity of psoriasis. The combination of redness, scaling, and thickness, as well as overall body involvement determine the PASI score. The scale ranges from 0 (best) to 72 (worst). | Week 64 | 
| Percentage of Treatment Response Based on Psoriasis Area and Severity Index (PASI) Score | PASI is a widely used tool for the measurement of severity of psoriasis. The combination of redness, scaling, and thickness, as well as overall body involvement determine the PASI score. The scale ranges from 0 (best) to 72 (worst). Percentage of Treatment Response= (Baseline PASI score-PASI score after treatment)/Baseline PASI score x 100. Baseline visit refers to Week 0. | Week 64 | 
| Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%), 90%, and Equal to 100% of Treatment Response Based on PASI Score | PASI is a widely used tool for the measurement of severity of psoriasis. The combination of redness, scaling, and thickness, as well as overall body involvement determine the PASI score. The scale ranges from 0 (best) to 72 (worst). Percentage of Treatment Response= (Baseline PASI score-PASI score after treatment)/Baseline PASI score x 100. Baseline visit refers to Week 0. | Week 64 | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 28, 40, 52 and 64 | The DLQI is a self-administered 10-item questionnaire that is used to assess 6 different aspects of 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). | Week 28, 40, 52 and 64 | 
| Change From Baseline in 36-Item Short Form Health Survey (SF-36) at Week 12, 28, 40, 52 and 64 | The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: (1) physical component summary (PCS)=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary (MCS)=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both sub scores and summary scores. For sub scores and summary scores: 0=worst score and 100=best score. | Week 12, 28, 40, 52 and 64 | 
| Change From Baseline in Psoriasis Disability Index (PDI) Score at Week 12, 28, 40, 52 and 64 | The PDI questionnaire consists of 15 questions relating to the impact of psoriasis in terms of daily activities, work or school, personal relationships, leisure, and treatment. Each question is scored on a scale of 0 (no impact) to 3 (greatest impact). The PDI is calculated by summing the scores of the questions resulting in a maximum score of 45 (greatest impact) and a minimum score of 0 (no impact). | Week 12, 28, 40, 52 and 64 | 
| Treatment Response Based on Nail Psoriasis Severity Index (NAPSI) Score | The NAPSI score is used to evaluate the severity of nail bed psoriasis and nail matrix psoriasis. The nail is divided with into quadrants and given a score for nail bed psoriasis (0-4) and nail matrix psoriasis (0-4) depending on the presence of any of the features of nail psoriasis in that quadrant. Each nail is evaluated, and the sum of all the nails is the total NAPSI score. The sum of the scores from all nails ranges from 0 (no psoriasis) to 80 (psoriasis present in all 4 quadrants of all 10 nails). | Week 12, 28, 40,52 and 64 | 
| Change From Baseline in the Number of Nails With Psoriasis Involvement at Week 12, 28, 40, 52 and 64 | The number of nails with psoriasis involvement was assessed by a dermatologist. | Week 12, 28, 40, 52 and 64 | 
| Change From Baseline in Joint Symptoms Expressed on a Visual Analogue Scale (VAS) at Week 12, 28, 40, 52 and 64 | Each participant will assess his/her pain associated with joint symptoms on each assessment day using a 100 mm VAS ranging from 0 mm (no pain) to 100 mm (the worst pain imaginable). | Week 12, 28, 40, 52 and 64 | 
| Percentage of Participants With Cleared (0), Cleared or Minimal (0 or 1) and Mild (Less Than or Equal to 2) Physician's Global Assessment (PGA) Score at Week 12 | Percentage of participants with PGA score of cleared (0), cleared or minimal (0 or 1) and mild (less than or equal to 2) was reported. The PGA score is a numeric scale which is completed by the physician and is designed to evaluate the physician's overall assessment of the participant's psoriasis. Overall lesions will be graded for induration (I), erythema (E), and scaling (S) as: 0=cleared, 1=minimal, 2=mild, 3=moderate, 4=marked, and 5=severe. The sum of the 3 scores (I + E + S) will be divided by 3 to obtain a final PGA score ranging from 0 [best] to 5 [worst]. | Week 12 | 
| Percentage of Participants With Cleared (0), Cleared or Minimal (0 or 1) and Mild (Less Than or Equal to 2) Physician's Global Assessment (PGA) Score at Week 64 | Percentage of participants with PGA score of cleared (0), cleared or minimal (0 or 1) and mild (less than or equal to 2) was reported. The PGA score is a numeric scale which is completed by the physician and is designed to evaluate the physician's overall assessment of the participant's psoriasis. Overall lesions will be graded for induration (I), erythema (E), and scaling (S) as: 0=cleared, 1=minimal, 2=mild, 3=moderate, 4=marked, and 5=severe. The sum of the 3 scores (I + E + S) will be divided by 3 to obtain a final PGA score ranging from 0 [best] to 5 [worst]. | Week 64 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis, Ustekinumab, CNTO 1275