A Study of the Safety and Efficacy of Ustekinumab in Patients With Psoriatic Arthritis With and Without Prior Exposure to Anti-TNF Agents

NCT ID: NCT01077362

Last Updated: 2014-02-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 312 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2012-11-30

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.

Conditions

Arthritis, Psoriatic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

placebo

Intervention Type: DRUG

SC injections

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.

Group Type: EXPERIMENTAL

placebo

Intervention Type: DRUG

SC injections

ustekinumab 45 mg

Intervention Type: DRUG

SC injections

ustekinumab 90 mg

Intervention Type: DRUG

SC injections

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.

Group Type: EXPERIMENTAL

placebo

Intervention Type: DRUG

SC injections

ustekinumab 90 mg

Intervention Type: DRUG

SC injections

Interventions

placebo

SC injections

Intervention Type: DRUG

ustekinumab 45 mg

SC injections

Intervention Type: DRUG

ustekinumab 90 mg

SC injections

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Birmingham, Alabama, United States

Huntsville, Alabama, United States

Los Angeles, California, United States

San Diego, California, United States

Denver, Colorado, United States

Trumbull, Connecticut, United States

Tampa, Florida, United States

Indianapolis, Indiana, United States

New Orleans, Louisiana, United States

Wheaton, Maryland, United States

Boston, Massachusetts, United States

Worcester, Massachusetts, United States

Edina, Minnesota, United States

Clayton, Missouri, United States

St Louis, Missouri, United States

Omaha, Nebraska, United States

Freehold, New Jersey, United States

Orchard Park, New York, United States

Rochester, New York, United States

Cleveland, Ohio, United States

Tulsa, Oklahoma, United States

Portland, Oregon, United States

Duncansville, Pennsylvania, United States

West Reading, Pennsylvania, United States

Dallas, Texas, United States

Graz, , Austria

Sankt Pölten, , Austria

Vienna, , Austria

Edmonton, Alberta, Canada

Kelowna, British Columbia, Canada

Vancouver, British Columbia, Canada

St. John's, Newfoundland and Labrador, Canada

Barrie, Ontario, Canada

Hamilton, Ontario, Canada

London, Ontario, Canada

North Bay, Ontario, Canada

Saint Catherines, Ontario, Canada

Sarnia, Ontario, Canada

Toronto, Ontario, Canada

Waterloo, Ontario, Canada

Windsor, Ontario, Canada

Montreal, Quebec, Canada

Sainte-Foy, Quebec, Canada

Trois-Rivières, Quebec, Canada

Bordeaux, , France

Chambray-lès-Tours, , France

Créteil, , France

Lille, , France

Paris, , France

Toulouse, , France

Berlin, , Germany

Cologne, , Germany

Erlangen, , Germany

Hamburg, , Germany

Herne, , Germany

München, , Germany

Debrecen, , Hungary

Szombathely, , Hungary

Veszprém, , Hungary

Bialystok, , Poland

Bydgoszcz, , Poland

Lublin, , Poland

Warsaw, , Poland

Moscow, , Russia

Saint Petersburg, , Russia

Yekaterinburg, , Russia

Gothenburg, , Sweden

Malmo, , Sweden

Stockholm, , Sweden

Uppsala, , Sweden

Cannock, , United Kingdom

Glasgow, , United Kingdom

London, , United Kingdom

Metropolitan Borough of Wirral, , United Kingdom

Newcastle upon Tyne, , United Kingdom

Salford, , United Kingdom

Sheffield, , United Kingdom

Southampton, , United Kingdom

Westcliff-on-Sea, , United Kingdom

Wigan, , United Kingdom

Countries

United States; Austria; Canada; France; Germany; Hungary; Poland; Russia; Sweden; United Kingdom

References

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Reference Type: DERIVED

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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.

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Reference Type: DERIVED

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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.

Reference Type: DERIVED

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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.

Reference Type: DERIVED

PMID: 27483458 (View on PubMed)

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.

Reference Type: DERIVED

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Other Identifiers

CNTO1275PSA3002

Identifier Type: OTHER

Identifier Source: secondary_id

2009-012265-60

Identifier Type: OTHER

Identifier Source: secondary_id

CR016483

Identifier Type: -

Identifier Source: org_study_id