Clinical trial NCT01009086: A Study of the Safety and Effectiveness of Ustekinumab in Patients With Psoriatic Arthritis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arthritis, Psoriatic
Keywords: Arthritis, Psoriatic
Ustekinumab
CNTO 1275
Stelara
Psoriasis
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2009-11-06
Enrollment: 615
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24.
timeFrame: Week 24
Secondary outcomes:
measure: Change From Baseline to Week 24 in the Disability Index Score as Measured With the "Disability Index of the Health Assessment Questionnaire" (HAQ-DI)
timeFrame: Day 1 (Baseline) and Week 24
measure: 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
timeFrame: Week 24
measure: Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 24
timeFrame: Week 24
measure: Percentage of Participants With American College of Rheumatology (ACR) 70 Response at Week 24
timeFrame: Week 24
measure: 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
timeFrame: Day 1 (Baseline) and Week 24
Other outcomes:
Locations:
city: Encinitas
country: United States
state: California
city: La Jolla
country: United States
state: California
city: San Diego
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Trumbull
country: United States
state: Connecticut
city: Tampa
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: New Orleans
country: United States
state: Louisiana
city: Wheaton
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Fall River
country: United States
state: Massachusetts
city: Worcester
country: United States
state: Massachusetts
city: Edina
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Freehold
country: United States
state: New Jersey
city: Norman
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Duncansville
country: United States
state: Pennsylvania
city: Wyomissing
country: United States
state: Pennsylvania
city: Jackson
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Webster
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Camperdown
country: Australia
city: Heidelberg
country: Australia
city: Maroochydore
country: Australia
city: Melbourne
country: Australia
city: Perth
country: Australia
city: Woodville
country: Australia
city: Graz
country: Austria
city: Innsbruck
country: Austria
city: Wien N/A
country: Austria
city: Wien
country: Austria
city: Edmonton
country: Canada
state: Alberta
city: Kelowna
country: Canada
state: British Columbia
city: Vancouver
country: Canada
state: British Columbia
city: Moncton
country: Canada
state: New Brunswick
city: St-John'S
country: Canada
state: Newfoundland and Labrador
city: St. John'S
country: Canada
state: Newfoundland and Labrador
city: Halifax
country: Canada
state: Nova Scotia
city: Barrie
country: Canada
state: Ontario
city: Hamilton
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: North Bay
country: Canada
state: Ontario
city: Sarnia
country: Canada
state: Ontario
city: St. Catherines
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Waterloo
country: Canada
state: Ontario
city: Windsor
country: Canada
state: Ontario
city: Trois-Rivieres
country: Canada
state: Quebec
city: Westmount
country: Canada
state: Quebec
city: Quebec
country: Canada
city: Helsinki
country: Finland
city: Hyvinkää
country: Finland
city: Berlin
country: Germany
city: Frankfurt
country: Germany
city: Hamburg
country: Germany
city: Herne
country: Germany
city: Kiel
country: Germany
city: Mahlow
country: Germany
city: Mainz
country: Germany
city: Regensburg
country: Germany
city: Tübingen
country: Germany
city: Budapest N/A
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Kecskemét
country: Hungary
city: Szeged
country: Hungary
city: Szolnok
country: Hungary
city: Veszprém
country: Hungary
city: Riga
country: Latvia
city: Alytus
country: Lithuania
city: Kaunas
country: Lithuania
city: Klaipeda
country: Lithuania
city: Siauliai
country: Lithuania
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: Rotorua
country: New Zealand
city: Wellington
country: New Zealand
city: Białystok
country: Poland
city: Bydgoszcz
country: Poland
city: Elblag
country: Poland
city: Lublin
country: Poland
city: Torun
country: Poland
city: Warszawa
country: Poland
city: Ekaterinburg
country: Russian Federation
city: Korolev
country: Russian Federation
city: Moscow
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Rostov-On-Don
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Saratov
country: Russian Federation
city: Barcelona
country: Spain
city: Oviedo
country: Spain
city: Santiago De Compostela
country: Spain
city: Sevilla
country: Spain
city: Cannock
country: United Kingdom
city: Glasgow
country: United Kingdom
city: London
country: United Kingdom
city: Salford
country: United Kingdom
city: Wigan
country: United Kingdom
city: Wirral
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.