An Effectiveness and Safety Study of CNTO 1275 in Patients With Active Psoriatic Arthritis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness and safety of CNTO 1275 (ustekinumab) in patients with psoriatic arthritis.

Detailed Description
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This study is a randomized (the study drug is assigned by chance), double-blind (neither physician nor the patient knows the treatment that the patient receives), parallel-group (each group of patients will be treated at the same time), multicenter study to evaluate the effectiveness and safety of CNTO 1275 compared to placebo in the treatment of patients with active psoriatic arthritis. Patients will be randomized in 1:1 ratio to 1 of 2 treatment groups (CNTO 1275 63 mg and placebo). Patients will be randomly assigned to receive study medication up to Week 12 and will be followed through Week 36 to monitor safety and efficacy. Patients randomly assigned to placebo will crossover to receive CNTO 1275 63 mg at Weeks 12 and 16. Patients randomly assigned to CNTO 1275 will receive placebo at Weeks 12 and 16 to maintain the blind. The duration of participation for an individual patient in the study will be up to 36 weeks.

Official Title
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A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of CNTO 1275, a Fully Human Anti-IL-12 Monoclonal Antibody, Administered Subcutaneously, in Subjects With Active Psoriatic Arthritis

Conditions
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Psoriatic Arthritis

Intervention / Treatment
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* Drug: CNTO 1275 63 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have had active psoriatic arthritis for at least 6 months prior to administration of first study injection Have an active plaque psoriasis (defined as a lesion of at least 2 cm in diameter), but not in armpits, on chest between breasts or groin Women of childbearing potential and all men must be using an effective method of birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) and must agree to continue to use such measures until 12 months after receiving the last injection of study agent Have an active arthritis despite disease-modifying anti-rheumatic drugs (DMARD) such as leflunomide, gold, sulfasalazine, but not including methotrexate) or non-steroidal anti-inflammatory agents (NSAID) such as aspirin, ibuprofen, naproxen) therapy. DMARD therapy is defined as taking a DMARD for at least 3 months, or evidence of not tolerating DMARD. NSAID therapy is defined as taking an NSAID for at least 4 weeks If the patients are using methotrexate (MTX), they should have started treatment at least 3 months prior to the first administration of study agent and should have no serious toxic side effects attributable to MTX Have no signs or symptoms suggestive of active tuberculosis upon medical history, physical examination and chest X-ray Exclusion Criteria: Have received DMARDs, other than methotrexate, within 4 weeks prior to the randomization visit Have used any biologic within the previous 3 months or 5 times the half-life of the biologic, whichever is longer Have received any oral, intravenous or intramuscular medications/treatments that could affect psoriasis (including, but not limited to, oral or injectable corticosteroids, retinoids, 1,25 dihydroxy vitamin D3 and analogues, psoralens, sulfasalazine, hydroxyurea, fumaric acid derivatives, or phototherapy) within 4 weeks of the randomization visit and/or have used topical medications/treatments that could affect psoriasis (eg, corticosteroids, anthralin, calcipotriene, topical vitamin D derivatives, retinoids, tazarotene, methoxsalen, trimethylpsoralens) within 2 weeks of the randomization visit Have a history of chronic or recurrent infectious disease, including but not limited to chronic renal infection, chronic chest infection (eg, bronchiectasis), recurrent urinary tract infection (recurrent pyelonephritis or chronic nonremitting cystitis), or open, draining, or infected skin wounds or ulcers Have a history of latent or active granulomatous infection, including tuberculosis (TB), histoplasmosis, or coccidioidomycosis, prior to screening Have current signs or symptoms of severe, progressive, or uncontrolled kidney, liver, blood, intestinal, hormonal, lung, heart, nervous, brain, or psychiatric disease Have any known cancer or have a history of cancer within the previous 5 years (with the following exception: have had basal cell carcinoma or squamous cell carcinoma in situ of the skin that has been treated, with no evidence of recurrence)

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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CNTO1275 (ustekinumab)<br>Group 1: Patients will receive CNTO 1275 63 mg at Weeks 0, 1, 2, and 3. At Weeks 12 and 16, patients will receive placebo to maintain the blind. | Drug: CNTO 1275 63 mg<br>* The patients will receive 90 mg (or 63 mg after filtration) subcutaneous injection on Weeks 0, 1, 2, and 3; Placebo subcutaneous injection on Weeks 12 and 16.<br>Drug: Placebo<br>* The patients will receive placebo subcutaneous injection on Weeks 0, 1, 2, and 3; At weeks 12 and 16 the patients will receive CNTo1275 90 mg (or 63 mg after filtration) subcutaneous injection<br>|
| Placebo Comparator: Placebo<br>Group 2: Patients will receive placebo at Weeks 0, 1, 2, and 3. At Weeks 12 and 16, patients will receive CNTO 1275 63 mg. | Drug: CNTO 1275 63 mg<br>* The patients will receive 90 mg (or 63 mg after filtration) subcutaneous injection on Weeks 0, 1, 2, and 3; Placebo subcutaneous injection on Weeks 12 and 16.<br>Drug: Placebo<br>* The patients will receive placebo subcutaneous injection on Weeks 0, 1, 2, and 3; At weeks 12 and 16 the patients will receive CNTo1275 90 mg (or 63 mg after filtration) subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With an American College of Rheumatology (ACR) 20 Response at Week 12 | ACR 20 response is an improvement of greater than or equal to 20 percentage in both tender and swollen joint count and in 3 to 5 assessments (patient's assessment of pain visual analog scale [VAS] with 0, no pain to 10, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity [0, very well to 10, very poor and 0, no arthritis activity to 10, extremely active, respectively]; Health Assessment Questionnaire [HAQ]: 20-questions on life activities [0, no difficulty to 3, inability to perform a task]; C-reactive protein[CRP]). | Week 0 to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 12 | ACR 50 response is an improvement of greater than or equal to 50 percentage in both tender and swollen joint count and in 3 to 5 assessments (patient's assessment of pain visual analog scale [VAS] with 0, no pain to 10, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity [0, very well to 10, very poor and 0, no arthritis activity to 10, extremely active, respectively]; Health Assessment Questionnaire [HAQ]: 20-questions on life activities [0, no difficulty to 3, inability to perform a task]; C-reactive protein[CRP]). | Week 12 | 
| Number of Participants With an American College of Rheumatology (ACR) 70 Response at Week 12 | ACR 70 response is an improvement of greater than or equal to 70 percentage in both tender and swollen joint count and in 3 to 5 assessments (patient's assessment of pain visual analog scale [VAS] with 0, no pain to 10, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity [0, very well to 10, very poor and 0, no arthritis activity to 10, extremely active, respectively]; Health Assessment Questionnaire [HAQ]: 20-questions on life activities [0, no difficulty to 3, inability to perform a task]; C-reactive protein[CRP]). | Week 12 | 
| Change in Health Assessment Questionnaire (HAQ) at Week 12 | The HAQ is a 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area based on the worst score from the questions that pertain to that task. The HAQ score is determined by the average of the 8 scores. | Week 0 to Week 12 | 
| Number of Participants With Psoriasis Area and Severity Index (PASI) Score of 75 Percent at Week 12 | Number of participants achieving greater than or equal to 75 perccentage mprovement PASI at Week 12. PASI is widely used tool for the measurement of severity of psoriasis. This is a test of how bad person's psoriasis is. The combine redness, scaling, and thickness, as well as overall body involvement determine the PASI score. The scale ranges from 0 (best) to 72 (worst). | 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, is designed to assess the impact of the disease on a participant's 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. The score ranges from 0 (better quality of life) to 30 (worse quality of life). | Week 0 to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriatic arthritis, CNTO 1275, Ustekinumab, Interleukin-23, IL-12, IL-23, Monoclonal antibodies