Clinical trial NCT00973479: An Effectiveness and Safety Study of Intravenous Golimumab in Patients With Active Rheumatoid Arthritis Despite Treatment With Methotrexate Therapy
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, an Anti-TNFalpha Monoclonal Antibody, Administered Intravenously, in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arthritis, Rheumatoid
Keywords: Arthritis, Rheumatoid
Active rheumatoid arthritis
Golimumab
CNTO148
Anti-TNFalpha monoclonal antibody
Methotrexate
Intravenous
Lead sponsor: Centocor, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Schering-Plough
First posted: 2009-09-09
Enrollment: 592
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 clinical effectiveness and safety of golimumab with methotrexate (MTX) in the treatment of rheumatoid arthritis (RA) when compared to MTX alone.

Detailed description: This is a randomized (study medication is assigned by chance), double-blind (neither physician nor participants knows the treatment that the participant receives), placebo-controlled (an inactive substance is compared with a medication to test whether the medication has a real effect in a clinical study), multicenter, 2-arm (2 groups) study of golimumab in participants with active RA despite concurrent MTX therapy. Approximately 564 participants will be randomly allocated to 1 of 2 treatment groups in a 2:1 ratio ie, Group 1(approximately 376 participants will receive golimumab + MTX) and Group 2 (approximately 188 participants will receive MTX + placebo). Total duration of study for each participant is 112 weeks. Safety will be evaluated by assessment of adverse events, tuberculosis testing and blood testing.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of rheumatoid arthritis (RA) for at least 3 months prior to screening
* 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 been on a stable MTX dose of 15 mg/week to 25 mg/week for at least 4 weeks prior to screening
* Have an active RA, as defined by disease activity with at least 6 swollen and 6 tender joints, at the time of screening and at baseline
* C-Reactive Protein greater than or equal to 1.0 mg/dL at screening
* No history of latent or active tuberculosis prior to screening

Exclusion Criteria:

* Other inflammatory diseases, including but not limited to psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, or lyme disease
* Treated with disease modifying agents (other than methotrexate)/systemic immunosuppressives (eg, D-penicillamine, hydroxychloroquine, chloroquine, oral or parenteral gold, sulfasalazine, leflunomide, azathioprine, cyclosporine, mycophenolate mofetil) during the 4 weeks prior to first administration of study agent
* Received intra-articular (in the joint), intramuscular (in the muscle), or intravenous corticosteroids, including adrenocorticotropic hormone, during the 4 weeks prior to first administration of study agent
* Known allergy to human immunoglobulin proteins or other components of golimumab
* Received any commercial or investigational anti-tumor necrosis factor alpha therapy such as but not exclusively infliximab, golimumab, adalimumab or etanercept

Primary outcomes:
measure: Proportion of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14
timeFrame: Week 14
Secondary outcomes:
measure: Proportion of Participants With Moderate or Good Response in Disease Activity Index Score 28 (DAS28) Using C-reactive Protein (CRP) at Week 14
timeFrame: Week 14
measure: Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Week 14
timeFrame: Week 14
measure: Proportion of Participants Who Achieved American College of Rheumatology (ACR) 50 Response at Week 24
timeFrame: Week 24
measure: Change From Baseline in Total Van Der Heijde Modified Sharp (vdH-S) Score at Week 24.
timeFrame: Week 24
Other outcomes:
Locations:
city: Daytona Beach
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: Moline
country: United States
state: Illinois
city: Wheaton
country: United States
state: Maryland
city: Worcester
country: United States
state: Massachusetts
city: Lincoln
country: United States
state: Nebraska
city: Cincinnati
country: United States
state: Ohio
city: Lubbock
country: United States
state: Texas
city: Buenos Aires N/A
country: Argentina
city: Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: Rosario
country: Argentina
city: San Juan
country: Argentina
city: San Miguel De Tucuman
country: Argentina
city: Santa Fe
country: Argentina
city: Cairns
country: Australia
city: Maroochydore
country: Australia
city: Melbourne
country: Australia
city: Woodville
country: Australia
city: Woolloongabba
country: Australia
city: Antioquia
country: Colombia
city: Barranquilla
country: Colombia
city: Bogota
country: Colombia
city: Cali Valley Del Cauca
country: Colombia
city: Medellin
country: Colombia
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Eger
country: Hungary
city: Gyor
country: Hungary
city: Gyula
country: Hungary
city: Szombathely
country: Hungary
city: Veszprem
country: Hungary
city: Anyang
country: Korea, Republic of
city: Dae-Gu
country: Korea, Republic of
city: Daejeon
country: Korea, Republic of
city: Incheon
country: Korea, Republic of
city: Pusan
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Alytus
country: Lithuania
city: Kaunas
country: Lithuania
city: Klaipeda
country: Lithuania
city: Siauliai
country: Lithuania
city: Vilnius
country: Lithuania
city: Georgetown
country: Malaysia
city: Ipoh
country: Malaysia
city: Johor Bahru
country: Malaysia
city: Kota Kinabalu
country: Malaysia
city: Kuantan
country: Malaysia
city: Kuching
country: Malaysia
city: Precinct 7
country: Malaysia
city: Selangor Darul Ehasan
country: Malaysia
city: Seremban
country: Malaysia
city: Guadalajara
country: Mexico
city: Leon
country: Mexico
city: Mexico
country: Mexico
city: Mex
country: Mexico
city: Monterrey
country: Mexico
city: Auckland
country: New Zealand
city: Takapuna Auckland
country: New Zealand
city: Timaru
country: New Zealand
city: Bialystok
country: Poland
city: Bydgoszcz
country: Poland
city: Dzialdowo
country: Poland
city: Elblag
country: Poland
city: Katowice
country: Poland
city: Lublin
country: Poland
city: Poznan
country: Poland
city: Sopot
country: Poland
city: Szczecin
country: Poland
city: Warszawa
country: Poland
city: Wloszczowa
country: Poland
city: Wrocław
country: Poland
city: Chelyabinsk
country: Russian Federation
city: Ekaterinburg
country: Russian Federation
city: Krasnoyarsk
country: Russian Federation
city: Moscow N/A
country: Russian Federation
city: Moscow
country: Russian Federation
city: Petrozavodsk
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Saratov
country: Russian Federation
city: St.Petersburg
country: Russian Federation
city: Donetsk
country: Ukraine
city: Ivano-Frankovsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Odessa
country: Ukraine
city: Simferopol
country: Ukraine
city: Ternopil
country: Ukraine
city: Vinnitsa
country: Ukraine
city: Zaporizhzhya
country: Ukraine
Study officials:
affiliation: Centocor, Inc.
name: Centocor, Inc. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Husni ME, Deodhar A, Schwartzman S, Chakravarty SD, Hsia EC, Leu JH, Zhou Y, Lo KH, Kavanaugh A. Pooled safety results across phase 3 randomized trials of intravenous golimumab in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Arthritis Res Ther. 2022 Mar 21;24(1):73. doi: 10.1186/s13075-022-02753-6.
citation: Lee JB, Broadwell A, Fan Y, Hu C, Adedokun OJ, Chakravarty SD, Zhou H, Xu Z, Leu JH. Population Pharmacokinetic and Exposure-Response Model Simulations: Predicted Exposure and Efficacy for Maintenance Doses of Intravenous Golimumab Every 6 or 8 Weeks in Patients With Moderately to Severely Active Rheumatoid Arthritis. Clin Ther. 2022 Mar;44(3):457-464.e2. doi: 10.1016/j.clinthera.2022.01.015. Epub 2022 Feb 17.
citation: Tesser J, Kafka S, DeHoratius RJ, Xu S, Hsia EC, Turkiewicz A. Efficacy and safety of intravenous golimumab plus methotrexate in patients with rheumatoid arthritis aged < 65 years and those >/= 65 years of age. Arthritis Res Ther. 2019 Aug 20;21(1):190. doi: 10.1186/s13075-019-1968-x.
citation: Standish KA, Huang CC, Curran ME, Schork NJ. Comprehensive analysis of treatment response phenotypes in rheumatoid arthritis for pharmacogenetic studies. Arthritis Res Ther. 2017 May 12;19(1):90. doi: 10.1186/s13075-017-1299-8.
citation: Bingham CO 3rd, Mendelsohn AM, Kim L, Xu Z, Leu J, Han C, Lo KH, Westhovens R, Weinblatt ME; GO-FURTHER Investigators. Maintenance of Clinical and Radiographic Benefit With Intravenous Golimumab Therapy in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy: Week-112 Efficacy and Safety Results of the Open-Label Long-Term Extension of a Phase III, Double-Blind, Randomized, Placebo-Controlled Trial. Arthritis Care Res (Hoboken). 2015 Dec;67(12):1627-36. doi: 10.1002/acr.22556.
citation: Bingham CO 3rd, Weinblatt M, Han C, Gathany TA, Kim L, Lo KH, Baker D, Mendelsohn A, Westhovens R. The effect of intravenous golimumab on health-related quality of life in rheumatoid arthritis: 24-week results of the phase III GO-FURTHER trial. J Rheumatol. 2014 Jun;41(6):1067-76. doi: 10.3899/jrheum.130864. Epub 2014 May 1.
citation: Weinblatt ME, Westhovens R, Mendelsohn AM, Kim L, Lo KH, Sheng S, Noonan L, Lu J, Xu Z, Leu J, Baker D, Bingham CO; GO-FURTHER investigators. Radiographic benefit and maintenance of clinical benefit with intravenous golimumab therapy in patients with active rheumatoid arthritis despite methotrexate therapy: results up to 1 year of the phase 3, randomised, multicentre, double blind, placebo controlled GO-FURTHER trial. Ann Rheum Dis. 2014 Dec;73(12):2152-9. doi: 10.1136/annrheumdis-2013-203742. Epub 2013 Sep 3.