A Study to Evaluate CNTO 1959 in the Treatment of Patients With Moderate to Severe Plaque-type Psoriasis

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 CNTO 1959 in the treatment of patients with moderate to severe plaque psoriasis.

Detailed Description
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This is a multicenter, dose-ranging study of CNTO 1959 in patients with moderate to severe plaque psoriasis. Patients who satisfy all inclusion and exclusion criteria will be assigned by chance to one of 7 treatment groups: a placebo group (a placebo is a treatment identical in appearance to CNTO 1959 but does not contain active drug), 1 of 5 dose groups for CNTO 1959, or adalimumab. Patients assigned to adalimumab will be dosed according to the labeled dosing for psoriasis. At Week 16, patients initially assigned to placebo will begin receiving CNTO 1959. Patients initially assigned to CNTO 1959 will continue to receive the same assigned dose level of study agent from Week 16 through Week 40. Patients receiving adalimumab will continue the labeled dosing regimen. All patients will be reassessed for clinical response every 4 weeks from Week 4 through Week 40. Patients will continue dosing through Week 40, with a subsequent efficacy and safety follow-up visit at Week 52. Patient safety will be monitored throughout the study.

Official Title
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A Phase 2 Multicenter, Randomized, Placebo- and Active-Comparator-Controlled, Dose-Ranging Trial to Evaluate CNTO 1959 for the Treatment of Subjects With Moderate to Severe Plaque-type Psoriasis (X-PLORE)

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: CNTO 1959 (5 mg)
* Drug: CNTO 1959 (15 mg)
* Drug: CNTO 1959 (50 mg)
* Drug: CNTO 1959 (100 mg)
* Drug: CNTO 1959 (200 mg)
* Drug: Adalimumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of plaque-type psoriasis with or without psoriatic arthritis for at least 6 months prior to first administration of any study agent Must be a candidate for phototherapy or systemic treatment for psoriasis (either new to treatment or having had previous treatment) Must be considered, in the opinion of the investigator, suitable candidates for adalimumab therapy If a woman, she must be postmenopausal, or if premenopausal, she must be either surgically sterile, practicing a highly effective method of birth control, or not heterosexually active during the study and for 5 months after receiving the last dose of study drug If a man, he must agree to use a double-barrier method of birth control (or must have been surgically sterilized) and to not donate sperm during the study and for 5 months after receiving the last dose of study drug. Exclusion Criteria: History of or current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease Has a contra-indication to anti-TNF therapy Has a history of chronic or recurrent infectious disease Has a nonplaque form of psoriasis or has drug-induced psoriasis Has been previously treated with adalimumab Has received any therapeutic agent directly targeted to IL-12, IL-17, or IL-23, (including but not limited to ustekinumab, briakinumab [ABT-874], AIN457, and SCH900222) within 6 months of the first administration of study agent.

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: CNTO 1959 (5 mg)<br>CNTO 1959 5 mg at weeks 0, 4, and 16, then every 12 weeks through Week 40 | Drug: CNTO 1959 (5 mg)<br>* Subcutaneous (SC) injections<br>|
| Experimental: CNTO 1959 (15 mg)<br>CNTO 1959 15 mg at weeks 0, 8, and 16, then every 8 weeks through Week 40 | Drug: CNTO 1959 (15 mg)<br>* SC injections<br>|
| Experimental: CNTO 1959 (50 mg)<br>CNTO 1959 50 mg at weeks 0, 4, and 16, then every 12 weeks through Week 40 | Drug: CNTO 1959 (50 mg)<br>* SC injections<br>|
| Experimental: CNTO 1959 (100 mg)<br>CNTO 1959 100 mg at weeks 0, 8, and 16, then every 8 weeks through Week 40 | Drug: CNTO 1959 (100 mg)<br>* SC injections<br>|
| Experimental: CNTO 1959 (200 mg)<br>CNTO 1959 200 mg at weeks 0, 4, and 16, then every 12 weeks through Week 40 | Drug: CNTO 1959 (200 mg)<br>* SC injections<br>|
| Active Comparator: Adalimumab (approved psoriasis dosing)<br>Adalimumab 80 mg at week 0 followed by 40 mg at week 1 and every second week through Week 39 (i.e., Weeks 3, 5, 7, etc.) | Drug: Adalimumab<br>* SC injections<br>|
| Placebo Comparator: Placebo to CNTO 1959 (100 mg)<br>Placebo at weeks 0, 4, and 8; then crossover to CNTO 1959 100 mg at Week 16, then every 8 weeks through Week 40 | Drug: CNTO 1959 (100 mg)<br>* SC injections<br>Drug: Placebo<br>* SC injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Physician Global Assessment (PGA) Score of Cleared (0) or Minimal (1) at Week 16 | PGA of psoriasis is used to determine the participant's psoriasis lesions overall at a given time point. Lesions were graded as erythema [0 (no evidence of plaque) to 5 (dusky to deep red coloration)], induration [0 (no plaque evaluation) to 5 (marked plaque evaluation)] and scaling [0 (no evidence of scaling) to 5 (severe; very thick tenacious scaling)]. The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the PGA score and category (0= cleared; 1= minimal; 2= mild; 3= moderate; 4= marked and 5= severe). | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75 Response at Week 16 | The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percentage (%)-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72. PASI 75 response was defined as at least a 75% reduction in PASI relative to Baseline. | Week 16 | 
| Difference in Percentage of Participants With Physician Global Assessment (PGA) Score of Cleared (0) or Minimal (1) in CNTO1959 Groups Compared With Adalimumab Group at Week 16 | PGA of psoriasis is used to determine the participant's psoriasis lesions overall at a given time point. Lesions were graded as erythema [0 (no evidence of plaque) to 5 (dusky to deep red coloration)], induration [0 (no plaque evaluation) to 5 (marked plaque evaluation)] and scaling [0 (no evidence of scaling) to 5 (severe; very thick tenacious scaling)]. The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the PGA score and category (0= cleared; 1= minimal; 2= mild; 3= moderate; 4= marked and 5= severe). | Week 16 | 
| Percentage of Participants With Physician Global Assessment (PGA) Score of Cleared (0) or Minimal (1) at Week 40 | PGA of psoriasis is used to determine the participant's psoriasis lesions overall at a given time point. Lesions were graded as erythema [0 (no evidence of plaque) to 5 (dusky to deep red coloration)], induration [0 (no plaque evaluation) to 5 (marked plaque evaluation)] and scaling [0 (no evidence of scaling) to 5 (severe; very thick tenacious scaling)]. The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the PGA score and category (0= cleared; 1= minimal; 2= mild; 3= moderate; 4= marked and 5= severe). | Week 40 | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 16 | The DLQI is a 10-item questionnaire that measures the impact of skin disease on participant's quality of life. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on quality of life. The DLQI total score ranges from 0 (not at all) to 30 (very much): 0-1 = no effect at all on the participant's life; 2-6 = small effect on the participant's life; 7-12 = moderate effect on the participant's life; 13-18 = very large effect on the participant's life; 19-30 = extremely large effect on the participant's life. Higher scores indicate more impact on quality of life of participants. | Baseline and Week 16 | 

 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, Psoriasis, Plaque-type psoriasis, CNTO 1959, adalimumab