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

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

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.

Study Overview

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

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 615
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia
  • Heidelberg, Australia
  • Maroochydore, Australia
  • Melbourne, Australia
  • Perth, Australia
  • Woodville, Australia
• Austria
  • Graz, Austria
  • Innsbruck, Austria
  • Wien, Austria
  • Wien N/A, Austria
• Canada
  • Quebec, Canada
  • Alberta
    • Edmonton, Alberta, Canada
  • British Columbia
    • Kelowna, British Columbia, Canada
    • Vancouver, British Columbia, Canada
  • New Brunswick
    • Moncton, New Brunswick, Canada
  • Newfoundland and Labrador
    • St-John'S, Newfoundland and Labrador, Canada
    • St. John'S, Newfoundland and Labrador, Canada
  • Nova Scotia
    • Halifax, Nova Scotia, 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
    • Trois-Rivieres, Quebec, Canada
    • Westmount, Quebec, Canada
• Finland
  • Helsinki, Finland
  • Hyvinkää, Finland
• Germany
  • Berlin, Germany
  • Frankfurt, Germany
  • Hamburg, Germany
  • Herne, Germany
  • Kiel, Germany
  • Mahlow, Germany
  • Mainz, Germany
  • Regensburg, Germany
  • Tübingen, Germany
• Hungary
  • Budapest, Hungary
  • Budapest N/A, Hungary
  • Debrecen, Hungary
  • Kecskemét, Hungary
  • Szeged, Hungary
  • Szolnok, Hungary
  • Veszprém, Hungary
• Latvia
  • Riga, Latvia
• Lithuania
  • Alytus, Lithuania
  • Kaunas, Lithuania
  • Klaipeda, Lithuania
  • Siauliai, Lithuania
• New Zealand
  • Auckland, New Zealand
  • Christchurch, New Zealand
  • Rotorua, New Zealand
  • Wellington, New Zealand
• Poland
  • Białystok, Poland
  • Bydgoszcz, Poland
  • Elblag, Poland
  • Lublin, Poland
  • Torun, Poland
  • Warszawa, Poland
• Russian Federation
  • Ekaterinburg, Russian Federation
  • Korolev, Russian Federation
  • Moscow, Russian Federation
  • Novosibirsk, Russian Federation
  • Rostov-On-Don, Russian Federation
  • Saint Petersburg, Russian Federation
  • Saratov, Russian Federation
• Spain
  • Barcelona, Spain
  • Oviedo, Spain
  • Santiago De Compostela, Spain
  • Sevilla, Spain
• United Kingdom
  • Cannock, United Kingdom
  • Glasgow, United Kingdom
  • London, United Kingdom
  • Salford, United Kingdom
  • Wigan, United Kingdom
  • Wirral, United Kingdom
• United States
  • California
    • Encinitas, California, United States
    • La Jolla, California, United States
    • San Diego, California, United States
  • Colorado
    • Denver, Colorado, United States
  • Connecticut
    • Trumbull, Connecticut, United States
  • Florida
    • Tampa, Florida, United States
  • Illinois
    • Chicago, Illinois, United States
  • Indiana
    • Indianapolis, Indiana, United States
  • Louisiana
    • New Orleans, Louisiana, United States
  • Maryland
    • Wheaton, Maryland, United States
  • Massachusetts
    • Boston, Massachusetts, United States
    • Fall River, Massachusetts, United States
    • Worcester, Massachusetts, United States
  • Minnesota
    • Edina, Minnesota, United States
  • Missouri
    • Saint Louis, Missouri, United States
  • Nebraska
    • Omaha, Nebraska, United States
  • New Jersey
    • Freehold, New Jersey, United States
  • Oklahoma
    • Norman, Oklahoma, United States
    • Tulsa, Oklahoma, United States
  • Oregon
    • Portland, Oregon, United States
  • Pennsylvania
    • Duncansville, Pennsylvania, United States
    • Wyomissing, Pennsylvania, United States
  • Tennessee
    • Jackson, Tennessee, United States
  • Texas
    • Houston, Texas, United States
    • Webster, Texas, United States
  • Washington
    • Seattle, Washington, 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
• 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 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 88. 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 88. 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 88. 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 88. 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 88. 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 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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) 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
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
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 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.	Day 1 (Baseline) and 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.
• Kavanaugh A, Puig L, Gottlieb AB, Ritchlin C, Li S, Wang Y, Mendelsohn AM, Song M, Zhu Y, Rahman P, McInnes IB; PSUMMIT 1 Study Group. Maintenance of Clinical Efficacy and Radiographic Benefit Through Two Years of Ustekinumab Therapy in Patients With Active Psoriatic Arthritis: Results From a Randomized, Placebo-Controlled Phase III Trial. Arthritis Care Res (Hoboken). 2015 Dec;67(12):1739-49. doi: 10.1002/acr.22645.
• McInnes IB, Kavanaugh A, Gottlieb AB, Puig L, Rahman P, Ritchlin C, Brodmerkel C, Li S, Wang Y, Mendelsohn AM, Doyle MK; PSUMMIT 1 Study Group. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet. 2013 Aug 31;382(9894):780-9. doi: 10.1016/S0140-6736(13)60594-2. Epub 2013 Jun 13.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: November 5, 2009
• First Submitted That Met QC Criteria: November 5, 2009
• First Posted (Estimate): November 6, 2009

Study Record Updates

• Last Update Posted (Estimate): March 3, 2015
• Last Update Submitted That Met QC Criteria: February 11, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: Psoriasis; Ustekinumab; CNTO 1275; Stelara; Arthritis, Psoriatic
• 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: CR016315; CNTO1275PSA3001 (Other Identifier: Janssen Research & Development, LLC); 2009-012264-14 (EudraCT Number)