Clinical trial NCT01077362: A Study of the Safety and Efficacy of Ustekinumab in Patients With Psoriatic Arthritis With and Without Prior Exposure to Anti-TNF Agents
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arthritis, Psoriatic
Keywords: Ustekinumab
CNTO 1275
Stelara
Psoriatic Arthritis
Psoriasis
TNF alpha
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2010-03-01
Enrollment: 312
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 efficacy (improvement of signs and symptoms) and safety of ustekinumab in patients with psoriatic arthritis.

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.

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 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

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: 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
measure: Percentage of Participants With American College of Rheumatology (ACR) 70 Response at Week 24
timeFrame: Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Los Angeles
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: 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: Worcester
country: United States
state: Massachusetts
city: Edina
country: United States
state: Minnesota
city: Clayton
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Freehold
country: United States
state: New Jersey
city: Orchard Park
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Cleveland
country: United States
state: Ohio
city: Tulsa
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Duncansville
country: United States
state: Pennsylvania
city: West Reading
country: United States
state: Pennsylvania
city: Dallas
country: United States
state: Texas
city: Graz
country: Austria
city: St Poelten N/A
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: St-John'S
country: Canada
state: Newfoundland and Labrador
city: St. John'S
country: Canada
state: Newfoundland and Labrador
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: Montreal
country: Canada
state: Quebec
city: Sainte-Foy
country: Canada
state: Quebec
city: Trois-Rivieres
country: Canada
state: Quebec
city: Bordeaux
country: France
city: Chambray-Les-Tours
country: France
city: Creteil
country: France
city: Lille
country: France
city: Paris Cedex 10
country: France
city: Toulouse N/A
country: France
city: Berlin
country: Germany
city: Erlangen
country: Germany
city: Hamburg
country: Germany
city: Herne
country: Germany
city: Köln
country: Germany
city: München
country: Germany
city: Debrecen
country: Hungary
city: Szombathely
country: Hungary
city: Veszprem
country: Hungary
city: Białystok
country: Poland
city: Bydgoszcz
country: Poland
city: Lublin
country: Poland
city: Warszawa
country: Poland
city: Ekaterinburg
country: Russian Federation
city: Moscow
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Göteborg
country: Sweden
city: Malmö
country: Sweden
city: Stockholm
country: Sweden
city: Uppsala
country: Sweden
city: Cannock
country: United Kingdom
city: Glasgow
country: United Kingdom
city: London
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Salford
country: United Kingdom
city: Sheffield
country: United Kingdom
city: Southampton
country: United Kingdom
city: Westcliff On Sea
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.