A Study of the Safety and Efficacy of Ustekinumab in Patients With Psoriatic Arthritis With and Without Prior Exposure to Anti-TNF Agents

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 3

Conditions: Arthritis, Psoriatic

Treatments: Drug: ustekinumab 45 mg; Drug: placebo; Drug: ustekinumab 90 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01077362

2009-012265-60 (Other Identifier)

CNTO1275PSA3002 (Other Identifier)

CR016483

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy (improvement of signs and symptoms) and safety of ustekinumab in patients with psoriatic arthritis.

Full description

This study is a randomized (patients are assigned different treatments based on chance), double-blind (neither the patient nor the physician knows whether drug or placebo is being taken, or at what dosage), parallel-group, multicenter study to evaluate the effectiveness and safety of ustekinumab compared to placebo in the treatment of patients with active psoriatic arthritis who have or are currently receiving treatment with a disease-modifying antirheumatic drug (DMARD) and/or a nonsteroidal anti-inflammatory drug (NSAID), including those who have previously received anti-tumor necrosis factor (anti-TNF) agents [(examples are infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira)]. The primary effectiveness endpoint will be measured by the reduction in signs and symptoms of arthritis, as defined by 20% improvement from baseline in American College of Rheumatology (ACR) measurements of arthritis at Week 24. The study will additionally look at higher levels of joint improvement (ie, 50% or 70% improvement from baseline) and improvement in activity and quality of life, as well as the impact of ustekinumab on psoriatic skin lesions. Safety assessments will be performed throughout the study and include obtaining and evaluating laboratory tests, vital signs (eg, blood pressure) and the occurrence and severity of adverse events (side effects). Patients will be assigned to one of three treatment groups. Patients will receive either 45 mg ustekinumab, 90 mg ustekinumab, or placebo at Weeks 0, 4 and every 12 weeks until Week 40. Patients who do not have >=5% improvement in their disease (tender and swollen joints) at Week 16 may be eligible to receive an increase or change to their ustekinumab dosage. Ustekinumab 45 mg, 90 mg, or placebo subcutaneous injections at Weeks 0 and 4 followed by every-12-week dosing with the last dose at Week 40. Early escape possibility at Week 16. Patients randomized to placebo will crossover to receive ustekinumab at Weeks 24 and 28 followed by every-12-week dosing with the last dose at Week 40. Expected duration of exposure to study agent including follow up for safety is 60 weeks.

Enrollment: 312 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have had a documented diagnosis of psoriatic arthritis (PsA) at least 6 months
• Have a diagnosis of active PsA at the time of entry into the study with at least 5 tender and 5 swollen joints at baseline
• May have previously received at least 8 weeks of etanercept, adalimumab, golimumab or certolizumab pegol or at least 14 weeks of infliximab or proven inability to tolerate anti-TNF therapy for 8-14 weeks
• If the patient is using methotrexate, they should have started treatment at a dose not to exceed 25 mg/week at least 3 months prior to the beginning of the study and should have no serious toxic side effects attributable to methotrexate

Exclusion criteria

• Have other inflammatory diseases, including but not limited to rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, or Lyme disease
• Have used any therapeutic agent targeted at reducing IL-12 or IL-23, including but not limited to ustekinumab and ABT-874
• Have used infliximab, golimumab or certolizumab pegol within 12 weeks of first study drug injection, or etanercept or adalimumab within 8 weeks of first study drug injection
• Have a medical history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to screening
• Have any known malignancy or have a history of malignancy (with the exception of basal cell carcinoma, squamous cell carcinoma in situ of the skin, or cervical carcinoma in situ that has been treated with no evidence of recurrence, or squamous cell carcinoma of the skin that has been treated with no evidence of recurrence within 5 years of the beginning of the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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312 participants in 3 patient groups

Placebo

Experimental group

Description:

Participants will receive subcutaneous (SC) injections of placebo at Weeks 0, 4, 16, and 20. At Week 24 participants will cross over to receive SC injections of ustekinumab 45 mg at Weeks 24 and 28 and every 12 weeks thereafter with the last dose at Week 40. If early escape, SC injections of 45 mg ustekinumab will be given at Weeks 16, 20, and 28 and every 12 weeks thereafter with the last dose at Week 40. For participants entering early escape, a SC placebo injection will be given at Week 24 to maintain the blind.

Treatment:

Drug: placebo

Ustekinumab 45 mg

Experimental group

Description:

Participants will receive SC injections of ustekinumab 45 mg at Weeks 0 and 4 and every 12 weeks thereafter with the last dose at Week 40. If early escape, SC injections of 90 mg ustekinumab will be given at Week 16 and every 12 weeks thereafter with the last dose at Week 40. Participants will receive SC injections of placebo at Weeks 20 and 24 to maintain the blind.

Treatment:

Drug: placebo

Drug: ustekinumab 45 mg

Drug: ustekinumab 90 mg

Ustekinumab 90 mg

Experimental group

Description:

Participants will receive SC injections of ustekinumab 90 mg at Weeks 0 and 4 and every 12 weeks thereafter with the last dose at Week 40. If early escape, the same dosage schedule will continue. Participants will receive SC injections of placebo at Weeks 20 and 24 to maintain the blind.

Treatment:

Drug: placebo

Drug: ustekinumab 90 mg