Clinical trial NCT00264550: An Efficacy and Safety Study of Golimumab in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlledTrial of Golimumab, a Fully Human Anti-TNFa MonoclonalAntibody, Administered Subcutaneously, in Subjects With ActiveRheumatoid Arthritis Despite Methotrexate Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Golimumab
Methotrexate
Fully Human anti-TNFa monoclonal antibody
Simpony
Lead sponsor: Centocor, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Schering-Plough
First posted: 2005-12-13
Enrollment: 444
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 and safety of golimumab, alone or in combination with methotrexate (MTX), as compared to methotrexate alone in rheumatoid arthritis (RA) patients who have active rheumatoid arthritis despite treatment with MTX.

Detailed description: This is a randomized (treatment is assigned by chance), double-blind (neither the physician nor the patient is aware of the received treatment), placebo-controlled study of multiple subcutaneous (SC) administrations of golimumab at 2 doses as monotherapy or in combination with MTX in patients with active RA despite treatment with MTX. The duration of participation in the study for an individual patient will be upto 268 weeks. The patients will be randomly assigned in a 3:3:2:2 ratio to receive golimumab 50 mg or 100 mg or placebo injections under the skin every 4 weeks through week 20 and methotrexate or placebo capsules will be given in addition. At Week 24, all subjects will receive golimumab 50mg or 100mg injections, and golimumab continues for all groups for about 4 and a half more years. At Week 16 any patient in the study who meets criteria for \< 20% improvement from baseline in both swollen and tender joint count will enter early escape in a double-blinded fashion. Treatment during the long-term extension will start at Week 52 and continue every 4 weeks thereafter for a total of approximately 5 years from the initial (Week 0) administration of study agent. Patients will return for scheduled follow-up visits generally every 12 weeks for a total length of follow-up of approximately 5 years from the first administration of the study drug.

Eligibility criteria: Inclusion Criteria:

* Have a diagnosis of rheumatoid arthritis (RA) (according to the revised 1987 criteria of the ACR) for at least 3 months prior to screening
* Must have been treated with and tolerated methotrexate (MTX) at a dose of at least 15 mg/week for at least 3 months prior to screening, and have a MTX dose of \>=15 mg/week and \<=25 mg/week and stable for at least 4 weeks prior to screening
* Have active RA as defined by persistent disease activity with at least 4 swollen and 4 tender joints, at the time of screening and baseline, and at least 2 of the following 4 criteria: a)C-reactive protein (CRP) \>=1.5 mg/dL at screening or erythrocyte sedimentation rate (ESR) by Westergren method of \>= 28 mm in the first hour at screening or baseline, b)Morning stiffness of \>= 30 minutes at screening and baseline, c)Bone erosion by x-ray and/or magnetic resonance imaging (MRI) prior to first administration of study agent, d)Anti-cyclic citrullinated peptide (anti-CCP) antibody-positive or rheumatoid factor (RF) positive at screening
* If using oral corticosteroids, must be on a stable dose equivalent to \<= 10 mg of prednisone/day for at least 2 weeks prior to first administration of study agent
* Are considered eligible according to specified tuberculosis (TB) screening criteria

Exclusion Criteria:

* Have inflammatory diseases other than RA that might confound the evaluation of the benefit of golimumab therapy
* Have had treatment with disease-modifying anti-rheumatic drugs (DMARDs)/systemic immunosuppressives other than MTX, during the 4 weeks prior to the first administration of study agent
* Have had prior treatment with biologic anti-tumor necrosis factor (TNF) drugs (infliximab, etanercept, adalimumab)
* Have had history of, or ongoing, chronic or recurrent infectious disease.
* Have serious infection within 2 months prior to first administration of study agent
* Have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to screening

Primary outcomes:
measure: Number of Participants Who Achieved American College of Rheumatology (ACR) 20 Response at Week 14
timeFrame: Week 14
measure: Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Week 24
timeFrame: Baseline (Week 0) and Week 24
Secondary outcomes:
measure: Number of Participants With Disease Activity Index Score 28 (DAS 28) Using C-reactive Protein (CRP) Response at Week 14
timeFrame: Week 14
measure: Number of Participants Who Achieved American College of Rheumatology 20 (ACR 20) Response at Week 24
timeFrame: Week 24
measure: Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Week 14
timeFrame: Baseline (Week 0) and Week 14
measure: Change From Baseline in Total Van Der Heijde Modified Sharp (vdH-S) Score at Week 24
timeFrame: Baseline (Week 0) and Week 24
Other outcomes:
Locations:
city: Mobile
country: United States
state: Alabama
city: Palo Alto
country: United States
state: California
city: Pasadena
country: United States
state: California
city: Upland
country: United States
state: California
city: Ormond Beach
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: Moline
country: United States
state: Illinois
city: Kansas City
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Lincoln
country: United States
state: Nebraska
city: Omaha
country: United States
state: Nebraska
city: Duncansville
country: United States
state: Pennsylvania
city: Richmond
country: United States
state: Virginia
city: Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: Rosario
country: Argentina
city: S.M. De Tucuman
country: Argentina
city: San Miguel De Tucuman
country: Argentina
city: Clayton
country: Australia
city: Maroochydore
country: Australia
city: Melbourne
country: Australia
city: Victoria
country: Canada
state: British Columbia
city: St. John'S
country: Canada
state: Newfoundland and Labrador
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Sainte Foy
country: Canada
state: Quebec
city: Hamilton Ontario
country: Canada
city: Rancagua
country: Chile
city: Santiago De Chile
country: Chile
city: Santiago
country: Chile
city: Temuco Ix
country: Chile
city: Berlin
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Köln
country: Germany
city: Leipzig
country: Germany
city: Rostock
country: Germany
city: Budepest
country: Hungary
city: Anyang
country: Korea, Republic of
city: Daegu
country: Korea, Republic of
city: Pusan
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Monterrey
country: Mexico
city: Auckland
country: New Zealand
city: Rotorua
country: New Zealand
city: Timaru
country: New Zealand
city: Elblag
country: Poland
city: Kalisz
country: Poland
city: Szczecin
country: Poland
city: Warsaw
country: Poland
city: Warszawa N/A
country: Poland
city: Kaohsiung County
country: Taiwan
Study officials:
affiliation: Centocor, Inc.
name: Centocor, Inc. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Leu JH, Adedokun OJ, Gargano C, Hsia EC, Xu Z, Shankar G. Immunogenicity of golimumab and its clinical relevance in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Rheumatology (Oxford). 2019 Mar 1;58(3):441-446. doi: 10.1093/rheumatology/key309.
citation: George MD, Ostergaard M, Conaghan PG, Emery P, Baker DG, Baker JF. Obesity and rates of clinical remission and low MRI inflammation in rheumatoid arthritis. Ann Rheum Dis. 2017 Oct;76(10):1743-1746. doi: 10.1136/annrheumdis-2017-211569. Epub 2017 Jun 12.
citation: Kay J, Fleischmann R, Keystone E, Hsia EC, Hsu B, Zhou Y, Goldstein N, Braun J. Five-year Safety Data from 5 Clinical Trials of Subcutaneous Golimumab in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis. J Rheumatol. 2016 Dec;43(12):2120-2130. doi: 10.3899/jrheum.160420. Epub 2016 Nov 1.
citation: Mack ME, Hsia E, Aletaha D. Comparative Assessment of the Different American College of Rheumatology/European League Against Rheumatism Remission Definitions for Rheumatoid Arthritis for Their Use as Clinical Trial End Points. Arthritis Rheumatol. 2017 Mar;69(3):518-528. doi: 10.1002/art.39945.
citation: Baker JF, Conaghan PG, Smolen JS, Aletaha D, Shults J, Emery P, Baker DG, Ostergaard M. Development and validation of modified disease activity scores in rheumatoid arthritis: superior correlation with magnetic resonance imaging-detected synovitis and radiographic progression. Arthritis Rheumatol. 2014 Apr;66(4):794-802. doi: 10.1002/art.38304.
citation: Keystone EC, Genovese MC, Hall S, Miranda PC, Bae SC, Palmer W, Wu Z, Xu S, Hsia EC. Golimumab in patients with active rheumatoid arthritis despite methotrexate therapy: results through 2 years of the GO-FORWARD study extension. J Rheumatol. 2013 Jul;40(7):1097-103. doi: 10.3899/jrheum.120584. Epub 2013 May 15.
citation: Genovese MC, Han C, Keystone EC, Hsia EC, Buchanan J, Gathany T, Murphy FT, Wu Z, Parasuraman S, Rahman MU. Effect of golimumab on patient-reported outcomes in rheumatoid arthritis: results from the GO-FORWARD study. J Rheumatol. 2012 Jun;39(6):1185-91. doi: 10.3899/jrheum.111195. Epub 2012 Apr 15.
citation: Visvanathan S, Rahman MU, Keystone E, Genovese M, Klareskog L, Hsia E, Mack M, Buchanan J, Elashoff M, Wagner C. Association of serum markers with improvement in clinical response measures after treatment with golimumab in patients with active rheumatoid arthritis despite receiving methotrexate: results from the GO-FORWARD study. Arthritis Res Ther. 2010;12(6):R211. doi: 10.1186/ar3188. Epub 2010 Nov 17.