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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Ustekinumab, a Fully Human Anti-IL-12/23p40 Monoclonal Antibody, Administered Subcutaneously, in Subjects With Active

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

Detailed Summary: 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
Sponsor: Janssen Research & Development, LLC

Current Primary Outcome: Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24. [ Time Frame: Week 24 ]

Original Primary Outcome: The proportion of patients with American College of Rheumatology (ACR) 20 response at Week 24. [ Time Frame: Week 24 ]

Current Secondary Outcome:

• Change From Baseline to Week 24 in the Disability Index Score as Measured With the "Disability Index of the Health Assessment Questionnaire" (HAQ-DI) [ Time Frame: Day 1 (Baseline) and Week 24 ]
  HAQ-DI is 20-question instrument that 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 (no difficulty), to 3 (inability to perform a task in that area). The average score across the functional areas yields an overall HAQ-DI score which ranges from 0 (no disability) to 3 (completely disabled). In psoriatic arthritis, a decrease in score of 0.30 indicates clinically meaningful improvement.
• Percentage of Participants (With >= 3% Baseline Body Surface Area (BSA) Psoriatic Involvement) Who Achieved a Psoriasis Area and Severity Index 75 (PASI 75) Response at Week 24 [ Time Frame: Week 24 ]
  The PASI is a physician-administered assessment tool used for assessing and grading the severity of psoriatic lesions and their response to therapy. The PASI produces a numeric score that can range from 0 (no disease) to 72 (maximal disease). A PASI 75 response is defined as greater than or equal to 75 percent improvement in PASI score from baseline.
• Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 24 [ Time Frame: Week 24 ]
  An ACR 50 response is defined as a greater than or equal to 50 percent improvement from baseline in swollen (66 joints) and tender (68 joints) joint counts and greater than or equal to 50 percent improvement in 3 of the following 5 assessments: 1) Participant's assessment of pain by Visual Analog Scale (VAS) (0-10 cm), 2) Participant's global assessment of disease activity by VAS (0-10 cm), 3) Physician's global assessment of disease activity by VAS (0-10 cm) 4) Participant's assessment of physical function as measured by the "Disability Index of the Health Assessment Questionnaire" (HAQ-DI) (score of 0-3 in 8 functional areas) and 5) C reactive protein.
• Change From Baseline to Week 24 in Total Modified Van Der Heijde-Sharp (vdH-S) Score for the Combined Radiographic Data From Studies CNTO1275PSA3001 and CNTO1275PSA3002 [ Time Frame: Day 1 (Baseline) and Week 24 ]
  The modified vdH-S score is a radiographic evaluation of hand and feet erosions and joint space narrowing (JSN) for 20 joints per hand and 6 joints per foot with a total score ranging from 0 (best) to 528 (worst = worst possible erosion score of 320 + worst possible JSN score of 208). Higher scores and positive score changes indicate more radiographic damage and radiographic progression, respectively. As per protocol, the analysis for this outcome measure used pooled data from 2 studies (CNTO1275PSA3001 and PSA3002) because initial power assumptions showed that 900 participants would be required to evaluate the impact of ustekinumab on structural damage (SD) progression. The 2 studies, (which had similar study designs and dosing regimens and differed only with regards to prior exposure to anti-TNFα therapies), were intended to independently measure efficacy in terms of signs, symptoms and physical function, while effects on SD progression would be provided from an integrated analysis.
• Percentage of Participants With American College of Rheumatology (ACR) 70 Response at Week 24 [ Time Frame: Week 24 ]
  An ACR 70 response is defined as a greater than or equal to 70 percent improvement from baseline in swollen (66 joints) and tender (68 joints) joint counts and greater than or equal to 70 percent improvement in 3 of the following 5 assessments: 1) Participant's assessment of pain by Visual Analog Scale (VAS) (0-10 cm), 2) Participant's global assessment of disease activity by VAS (0-10 cm), 3) Physician's global assessment of disease activity by VAS (0-10 cm) 4) Participant's assessment of physical function as measured by the "Disability Index of the Health Assessment Questionnaire" (HAQ-DI) (score of 0-3 in 8 functional areas) and 5) C reactive protein.

Original Secondary Outcome:

• The change from baseline in total radiographic scores of the hands and feet at Week 24. [ Time Frame: Week 24 ]
• The change from baseline in the Health Assessment Questionnaire score at Week 24. [ Time Frame: Week 24 ]
• The proportion of patients with American College of Rheumatology (ACR) 50 and ACR 70 responses at Week 24. [ Time Frame: Week 24 ]
• The proportion of patients (with baseline = 3% body surface area (BSA) psoriatic involvement) who achieve a Psoriasis Area and Severity Index (PASI) 75 response at Week 24. [ Time Frame: Week 24 ]
• The change from baseline in the Physical Component Score (PCS) and the Mental Component Score (MCS) of the Short Form-36 Health Survey at Week 24 [ Time Frame: Week 24 ]

Dates:
Date Received: February 25, 2010
Date Started: March 2010
Date Completion:
Last Updated: January 22, 2014
Last Verified: January 2014