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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01077362
First received: February 25, 2010
Last updated: January 22, 2014
Last verified: January 2014

February 25, 2010
January 22, 2014
March 2010
March 2012   (final data collection date for primary outcome measure)
Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24. [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
An ACR 20 response is defined as a greater than or equal to 20 percent improvement from baseline in swollen (66 joints) and tender (68 joints) joint counts and greater than or equal to 20 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.
The proportion of patients with American College of Rheumatology (ACR) 20 response at Week 24. [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01077362 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.
  • The change from baseline in total radiographic scores of the hands and feet at Week 24. [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • The change from baseline in the Health Assessment Questionnaire score at Week 24. [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • The proportion of patients with American College of Rheumatology (ACR) 50 and ACR 70 responses at Week 24. [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study of the Safety and Efficacy of Ustekinumab in Patients With Psoriatic Arthritis With and Without Prior Exposure to Anti-TNF Agents
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 Psoriatic Arthritis Including Those Previously Treated With Biologic Anti-TNFalpha Agent(s)

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

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Arthritis, Psoriatic
  • Drug: placebo
    SC injections
  • Drug: ustekinumab 45 mg
    SC injections
  • Drug: ustekinumab 90 mg
    SC injections
  • Experimental: Placebo
    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.
    Intervention: Drug: placebo
  • Experimental: Ustekinumab 45 mg
    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.
    Interventions:
    • Drug: placebo
    • Drug: ustekinumab 45 mg
    • Drug: ustekinumab 90 mg
  • Experimental: Ustekinumab 90 mg
    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.
    Interventions:
    • Drug: placebo
    • Drug: ustekinumab 90 mg
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
312
November 2012
March 2012   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada,   United States,   Austria,   United Kingdom,   France,   Germany,   Hungary,   Poland,   Russian Federation,   Sweden
 
NCT01077362
CR016483, CNTO1275PSA3002, 2009-012265-60
Yes
Janssen Research & Development, LLC
Janssen Research & Development, LLC
Not Provided
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Janssen Research & Development, LLC
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP