Clinical trial NCT00264537: A Study of the Safety and Efficacy of Golimumab in Subjects With Rheumatoid Arthritis That Are Methotrexate-naive
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlledTrial of Golimumab, a Fully Human Anti-TNFa MonoclonalAntibody, Administered Subcutaneously, in Methotrexate-naive Subjects With Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Methotrexate Naïve
subcutaneous injection
Lead sponsor: Centocor, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Schering-Plough
First posted: 2005-12-13
Enrollment: 637
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, as compared to methotrexate alone in rheumatoid arthritis subjects who have not been previously treated with methotrexate.

Detailed description: Golimumab is a fully human protein (antibody) which binds to tumor necrosis factor (TNFa). TNFa is increased in patients with rheumatoid arthritis (RA), and plays a major role in causing the joint pain, swelling, and damage from RA. Other marketed drugs that target TNFa (anti-TNFa drugs) have been shown to be effective in reducing the symptoms, signs, and joint damage of RA, but have limitations with respect to safety and ease of use. This is a randomized, double-blind, placebo-controlled trial of the efficacy and safety of a new anti-TNFa drug, golimumab, at 2 doses, injected under the skin every 4 weeks, alone or in combination with methotrexate, compared with methotrexate alone, in subjects with active RA who have not been previously treated with methotrexate. The study hypothesis is that golimumab, alone or in combination with methotrexate, will be more effective in treatment of RA than methotrexate alone, as measured by the American College of Rheumatology (ACR) response criteria and change from baseline in van der Heide Modified Sharp (vdH-S) score, without causing unacceptable significant adverse effects. The ACR response criteria were designed to determine the percentage of subjects who have achieved a certain level of improvement in their signs and symptoms of rheumatoid arthritis. The vdH-S score is a measurement of the amount of joint damage in a subject as seen by x-ray. Other secondary measures of effectiveness include the Health Assessment Questionnaire (HAQ), which is a series of questions that measure a subject's impairment in physical function caused by RA. Golimumab 50 mg or 100 mg, or placebo injections under the skin every 4 weeks until Week52. Methotrexate (MTX) or placebo capsules will be given in addition. At Week52, subjects on MTX alone with joint pain or swelling get golimumab 50mg, and all subjects receive golimumab for about 4 more years.

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 first administration of study agent
* Are methotrexate (MTX)-naïve (ie, have not received more than 3 weekly doses of MTX for RA at any time)
* 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 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.

Exclusion Criteria:

* Can not have inflammatory diseases other than RA that might confound the evaluation of the benefit of golimumab therapy
* No treatment with disease-modifying anti-rheumatic drugs (DMARDs)/systemic immunosuppressives during the 4 weeks prior to the first administration of study agent
* No prior treatment with biologic anti-TNF drugs (infliximab, etanercept, adalimumab)
* No history of, or ongoing, chronic or recurrent infectious disease
* No serious infection within 2 months prior to first administration of study agent.

Primary outcomes:
measure: Number 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 52
timeFrame: Baseline and Week 52
Secondary outcomes:
measure: Number of Participants Who Achieved American College of Rheumatology (ACR) 20 Response at Week 24
timeFrame: Week 24
measure: Number of Patients With Abnormal Baseline C-reactive Protein (CRP) 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 52 in Patients With Abnormal C-reactive Protein (CRP Greater Than 1.0 mg/dL) at Baseline
timeFrame: Baseline and Week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Mobile
country: United States
state: Alabama
city: Upland
country: United States
state: California
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Coeur D'Alene
country: United States
state: Idaho
city: Moline
country: United States
state: Illinois
city: Springfield
country: United States
state: Illinois
city: Kansas City
country: United States
state: Kansas
city: Witchita
country: United States
state: Kansas
city: Saint Paul
country: United States
state: Minnesota
city: Kansas City
country: United States
state: Missouri
city: Lincoln
country: United States
state: Nebraska
city: Charlotte
country: United States
state: North Carolina
city: Duncansville
country: United States
state: Pennsylvania
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Lubbock
country: United States
state: Texas
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: Maroochydore
country: Australia
city: Melbourne
country: Australia
city: Wien
country: Austria
city: Brussels
country: Belgium
city: Liege
country: Belgium
city: Winnipeg
country: Canada
state: Manitoba
city: St. John'S
country: Canada
state: Newfoundland and Labrador
city: Rancagua
country: Chile
city: Santiago
country: Chile
city: Budapest
country: Hungary
city: Gyula
country: Hungary
city: Szombathely
country: Hungary
city: Bangalore
country: India
city: Lucknow Gpo
country: India
city: Secunderabad
country: India
city: Daejeon
country: Korea, Republic of
city: Incheon
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Suwon
country: Korea, Republic of
city: Precinct 7
country: Malaysia
city: Saemban
country: Malaysia
city: Selayang N/A
country: Malaysia
city: Auckland
country: New Zealand
city: Timaru
country: New Zealand
city: Cebu
country: Philippines
city: Manila
country: Philippines
city: Quezon
country: Philippines
city: Bialystok
country: Poland
city: Elblag
country: Poland
city: Kalisz
country: Poland
city: Szczecin
country: Poland
city: Warsaw
country: Poland
city: Moscow
country: Russian Federation
city: Saratov
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Singapore
country: Singapore
city: Madrid
country: Spain
city: Santander
country: Spain
city: Sevilla N/A
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Kaohsiung
country: Taiwan
city: Taichung
country: Taiwan
city: Taipei
country: Taiwan
city: Tiachung
country: Taiwan
city: Bangkok
country: Thailand
city: Chiang Mai
country: Thailand
city: Dnipropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kiev
country: Ukraine
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Centocor, Inc.
name: Centocor, Inc. Clinical Trial
role: STUDY_DIRECTOR
References:
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: Baker JF, Conaghan PG, Emery P, Baker DG, Ostergaard M. Relationship of patient-reported outcomes with MRI measures in rheumatoid arthritis. Ann Rheum Dis. 2017 Mar;76(3):486-490. doi: 10.1136/annrheumdis-2016-209463. Epub 2016 Jul 18.
citation: Emery P, Fleischmann RM, Hsia EC, Xu S, Zhou Y, Baker D. Efficacy of golimumab plus methotrexate in methotrexate-naive patients with severe active rheumatoid arthritis. Clin Rheumatol. 2014 Sep;33(9):1239-46. doi: 10.1007/s10067-014-2731-y. Epub 2014 Jul 9.
citation: Emery P, Fleischmann RM, Doyle MK, Strusberg I, Durez P, Nash P, Amante E, Churchill M, Park W, Pons-Estel B, Xu W, Xu S, Wu Z, Hsia EC. Golimumab, a human anti-tumor necrosis factor monoclonal antibody, injected subcutaneously every 4 weeks in patients with active rheumatoid arthritis who had never taken methotrexate: 1-year and 2-year clinical, radiologic, and physical function findings of a phase III, multicenter, randomized, double-blind, placebo-controlled study. Arthritis Care Res (Hoboken). 2013 Nov;65(11):1732-42. doi: 10.1002/acr.22072.
citation: Ostergaard M, Emery P, Conaghan PG, Fleischmann R, Hsia EC, Xu W, Rahman MU. Significant improvement in synovitis, osteitis, and bone erosion following golimumab and methotrexate combination therapy as compared with methotrexate alone: a magnetic resonance imaging study of 318 methotrexate-naive rheumatoid arthritis patients. Arthritis Rheum. 2011 Dec;63(12):3712-22. doi: 10.1002/art.30592.