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.

Study Overview

• Status: Completed
• Conditions: Arthritis, Psoriatic
• Intervention / Treatment: Drug: placebo; Drug: ustekinumab 45 mg; Drug: ustekinumab 90 mg

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 312
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria
  • St Poelten N/A, Austria
  • Wien, Austria
  • Wien N/A, Austria
• Canada
  • Alberta
    • Edmonton, Alberta, Canada
  • British Columbia
    • Kelowna, British Columbia, Canada
    • Vancouver, British Columbia, Canada
  • Newfoundland and Labrador
    • St-John'S, Newfoundland and Labrador, Canada
    • St. John'S, Newfoundland and Labrador, Canada
  • Ontario
    • Barrie, Ontario, Canada
    • Hamilton, Ontario, Canada
    • London, Ontario, Canada
    • North Bay, Ontario, Canada
    • Sarnia, Ontario, Canada
    • St. Catherines, Ontario, Canada
    • Toronto, Ontario, Canada
    • Waterloo, Ontario, Canada
    • Windsor, Ontario, Canada
  • Quebec
    • Montreal, Quebec, Canada
    • Sainte-Foy, Quebec, Canada
    • Trois-Rivieres, Quebec, Canada
• France
  • Bordeaux, France
  • Chambray-Les-Tours, France
  • Creteil, France
  • Lille, France
  • Paris Cedex 10, France
  • Toulouse N/A, France
• Germany
  • Berlin, Germany
  • Erlangen, Germany
  • Hamburg, Germany
  • Herne, Germany
  • Köln, Germany
  • München, Germany
• Hungary
  • Debrecen, Hungary
  • Szombathely, Hungary
  • Veszprem, Hungary
• Poland
  • Białystok, Poland
  • Bydgoszcz, Poland
  • Lublin, Poland
  • Warszawa, Poland
• Russian Federation
  • Ekaterinburg, Russian Federation
  • Moscow, Russian Federation
  • St Petersburg, Russian Federation
• Sweden
  • Göteborg, Sweden
  • Malmö, Sweden
  • Stockholm, Sweden
  • Uppsala, Sweden
• United Kingdom
  • Cannock, United Kingdom
  • Glasgow, United Kingdom
  • London, United Kingdom
  • Newcastle Upon Tyne, United Kingdom
  • Salford, United Kingdom
  • Sheffield, United Kingdom
  • Southampton, United Kingdom
  • Westcliff On Sea, United Kingdom
  • Wigan, United Kingdom
  • Wirral, United Kingdom
• United States
  • Alabama
    • Birmingham, Alabama, United States
    • Huntsville, Alabama, United States
  • California
    • Los Angeles, California, United States
    • San Diego, California, United States
  • Colorado
    • Denver, Colorado, United States
  • Connecticut
    • Trumbull, Connecticut, United States
  • Florida
    • Tampa, Florida, United States
  • Indiana
    • Indianapolis, Indiana, United States
  • Louisiana
    • New Orleans, Louisiana, United States
  • Maryland
    • Wheaton, Maryland, United States
  • Massachusetts
    • Boston, Massachusetts, United States
    • Worcester, Massachusetts, United States
  • Minnesota
    • Edina, Minnesota, United States
  • Missouri
    • Clayton, Missouri, United States
    • Saint Louis, Missouri, United States
  • Nebraska
    • Omaha, Nebraska, United States
  • New Jersey
    • Freehold, New Jersey, United States
  • New York
    • Orchard Park, New York, United States
    • Rochester, New York, United States
  • Ohio
    • Cleveland, Ohio, United States
  • Oklahoma
    • Tulsa, Oklahoma, United States
  • Oregon
    • Portland, Oregon, United States
  • Pennsylvania
    • Duncansville, Pennsylvania, United States
    • West Reading, Pennsylvania, United States
  • Texas
    • Dallas, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: placebo; SC injections
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.	Drug: placebo; SC injections; Drug: ustekinumab 45 mg; SC injections; Drug: ustekinumab 90 mg; SC injections
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.	Drug: placebo; SC injections; Drug: ustekinumab 90 mg; SC injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 24 in the Disability Index Score as Measured With the "Disability Index of the Health Assessment Questionnaire" (HAQ-DI)	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
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
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
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 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.	Day 1 (Baseline) and Week 24
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

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Ghosh S, Gensler LS, Yang Z, Gasink C, Chakravarty SD, Farahi K, Ramachandran P, Ott E, Strober BE. Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn's Disease: An Integrated Analysis of Phase II/III Clinical Development Programs. Drug Saf. 2019 Jun;42(6):751-768. doi: 10.1007/s40264-019-00797-3. Erratum In: Drug Saf. 2019 Apr 22;:
• Helliwell PS, Gladman DD, Chakravarty SD, Kafka S, Karyekar CS, You Y, Campbell K, Sweet K, Kavanaugh A, Gensler LS. Effects of ustekinumab on spondylitis-associated endpoints in TNFi-naive active psoriatic arthritis patients with physician-reported spondylitis: pooled results from two phase 3, randomised, controlled trials. RMD Open. 2020 Feb;6(1):e001149. doi: 10.1136/rmdopen-2019-001149.
• Siebert S, Sweet K, Dasgupta B, Campbell K, McInnes IB, Loza MJ. Responsiveness of Serum C-Reactive Protein, Interleukin-17A, and Interleukin-17F Levels to Ustekinumab in Psoriatic Arthritis: Lessons From Two Phase III, Multicenter, Double-Blind, Placebo-Controlled Trials. Arthritis Rheumatol. 2019 Oct;71(10):1660-1669. doi: 10.1002/art.40921. Epub 2019 Sep 3.
• Rahman P, Puig L, Gottlieb AB, Kavanaugh A, McInnes IB, Ritchlin C, Li S, Wang Y, Song M, Mendelsohn A, Han C; PSUMMIT 1 and 2 Study Groups. Ustekinumab Treatment and Improvement of Physical Function and Health-Related Quality of Life in Patients With Psoriatic Arthritis. Arthritis Care Res (Hoboken). 2016 Dec;68(12):1812-1822. doi: 10.1002/acr.23000. Epub 2016 Oct 21.
• Kavanaugh A, Puig L, Gottlieb AB, Ritchlin C, You Y, Li S, Song M, Randazzo B, Rahman P, McInnes IB. Efficacy and safety of ustekinumab in psoriatic arthritis patients with peripheral arthritis and physician-reported spondylitis: post-hoc analyses from two phase III, multicentre, double-blind, placebo-controlled studies (PSUMMIT-1/PSUMMIT-2). Ann Rheum Dis. 2016 Nov;75(11):1984-1988. doi: 10.1136/annrheumdis-2015-209068. Epub 2016 Apr 20.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: February 25, 2010
• First Submitted That Met QC Criteria: February 26, 2010
• First Posted (Estimate): March 1, 2010

Study Record Updates

• Last Update Posted (Estimate): February 27, 2014
• Last Update Submitted That Met QC Criteria: January 22, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Psoriasis; Psoriatic Arthritis; TNF alpha; Ustekinumab; CNTO 1275; Stelara
• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic; Dermatologic Agents; Ustekinumab
• Other Study ID Numbers: CR016483; CNTO1275PSA3002 (Other Identifier: Janssen Research & Development, LLC); 2009-012265-60 (Other Identifier: Janssen Research & Development, LLC)