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

Arthritis, Psoriatic Clinical Trial

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 Psoriatic Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01009086
• Other study ID #: CR016315
• Secondary ID: CNTO1275PSA30012
• Status: Completed
• Phase: Phase 3
• First received: November 5, 2009
• Last updated: February 11, 2015
• Start date: December 2009
• Est. completion date: May 2013

Study information

• Verified date: February 2015
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Ethics CommissionGreat Britain: Medicines and Healthcare Products Regulatory AgencyHungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Other known NCT identifiers

• NCT01902706

Recruitment information / eligibility

• Status: Completed
• Enrollment: 615
• Est. completion date: May 2013
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

• If the participant is using methotrexate they should have started treatment at a dose not to exceed 25 milligram per week at least 3 months prior to the beginning of the study and should have no serious toxic side effects attributable to methotrexate. Methotrexate route of administration and doses should be stable for at least 4 weeks prior to the first administration of study agent. If currently not using methotrexate, must have not received methotrexate for at least 4 weeks prior to the first administration of the study agent

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 interleukin (IL)-12 or IL-23, including but not limited to ustekinumab and briakinumab (ABT-874)

• Have used any biologic agents that are targeted for reducing tumor necrosis factor-alpha, including but not limited to infliximab, etanercept, adalimumab, and golimumab

• Have a medical history of latent or active granulomatous infection

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic

Intervention

Drug:
• Placebo
SC injections
• Ustekinumab 45 mg
SC injections
• Ustekinumab 90 mg
SC injections

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Finland,  Germany,  Hungary,  Latvia,  Lithuania,  New Zealand,  Poland,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24.	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 centimeters [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.	Week 24	No
Secondary	Change From Baseline to Week 24 in the Disability Index Score as Measured With the "Disability Index of the Health Assessment Questionnaire" (HAQ-DI)	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.	Day 1 (Baseline) and Week 24	No
Secondary	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	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.	Week 24	No
Secondary	Percentage of Participants With American College of Rheumatology (ACR) 50 Response at 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.	Week 24	No
Secondary	Percentage of Participants With American College of Rheumatology (ACR) 70 Response at 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.	Week 24	No
Secondary	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	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 (TNFa) 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.	Day 1 (Baseline) and Week 24	No