Clinical Trial: A Study of the Safety and Effectiveness of Ustekinumab in Patients With Psoriatic Arthritis

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 Aanti-IL-12/23p40 Monoclonal Antibody, Administered Subcutaneously, in Subjects With Active

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

Detailed Summary: This is a randomized (participants are assigned different treatments based on chance), double-blind (neither the participant nor the physician knows whether drug or placebo is being taken, or at what dosage), parallel-group (each group of participants will be treated at the same time), and multicenter (study conducted at multiple sites) study. Approximately, 615 participants will participate in this study. Participants will be assigned to one of three treatment groups: Group I: ustekinumab 45 mg, Group II: ustekinumab 90 mg, and Group III: placebo group (an inactive substance). Participants will receive either 45 mg ustekinumab or 90 mg ustekinumab at Weeks 0, 4, and every 12 weeks until Week 88 as randomized to respective groups. Participants in placebo group will receive placebo at Weeks 0, 4, 16, and 20 and 45 mg ustekinumab at Weeks 24 and 28 followed by every 12 weeks dosing until Week 88. Participants who do not have greater than or equal to 5 percentage improvement in their disease (tender and swollen joints) will be eligible for an early escape. Specifically, during early escape at Week 16, participants in Group I will receive 90 mg ustekinumab, for participants in Group II same dosing schedule will be continued, and participants in placebo group will receive 45 mg ustekinumab. Safety evaluations will include assessments of adverse events, clinical laboratory tests, and physical examination. The maximum study duration will be approximately 108 weeks.
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 ]
  The 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.
• 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.
• 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 score and positive score changes indicate more radiographic damage and radiographic progression, respectively. As per protocol, 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 impact of ustekinumab on structural damage (SD) progression. The 2 studies, (which had similar study designs and dosing regimens with difference to prior exposure to anti-tumor necrosis factor alpha (TNFα) therapies), were intended to independently measure efficacy in terms of signs, symptoms and physical function, while effects on SD progression is provided from an integrated analysis.

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 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 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: November 5, 2009
Date Started: December 2009
Date Completion:
Last Updated: February 11, 2015
Last Verified: February 2015