Back to resultsA Study of Safety and Effectiveness of Golimumab in Participants With Active Rheumatoid Arthritis Despite Methotrexate Therapy
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Golimumab
Methotrexate
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid arthritis, Golimumab, Methotrexate, Tumor Necrosis Factor-alpha, Immunology
Eligibility Criteria
Inclusion Criteria: - Must have a diagnosis of active rheumatoid arthritis (RA) (according to the revised 1987 criteria of the ARA (American Rheumatism Association) with at least 4 swollen and 4 tender joints for at least 3 months prior to screening - Have been treated with and tolerated methotrexate (MTX) at a dose of at least 15 mg per week for at least 3 months prior to screening - Have been on a stable MTX dose of greater than or equal to 15 mg per week and less than or eual to 25 mg per week for at least 4 weeks prior to screening - If using non steroidal anti-inflammatory agents (such as naproxen) or other pain relievers for RA, must be on a stable dose for at least 2 weeks prior to the first administration of study agent Exclusion Criteria: - Participants having known hypersensitivity (severe allergy) to human immunoglobulin proteins or other components of golimumab - Having known clinically serious adverse reaction to a biologic anti-TNF agent - Have had history of latent or active granulomatous infection, including tuberculosis, histoplasmosis, or coccidioidomycosis, prior to screening
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Group I: 2mg/kg Golimumab + MTX
Group II: 2mg/kg Golimumab only
Group III: 4mg/kg Golimumab + MTX
Group IV: 4mg/kg Golimumab only
Group V: IV Placebo + MTX
Arm Description
Intravenous (IV) infusions of 2mg/kg golimumab at Week 0 and every 12 weeks thereafter with early escape (an additional 2mg/kg IV infusion of golimumab) and dose regimen adjustment (switch to 4mg/kg IV golimumab), depending on joint assessment results, at Week 16 and 24, respectively. The duration of the combined IV treatment period (initial treatment plus early escape and/or dose regimen adjustment) will be a minimum of 48 weeks. The IV treatment period will be followed by the option of subcutaneous (SC) injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition, patients will receive methotrexate (MTX) at the same dose as that before study entry
IV infusions of 2mg/kg golimumab at Week 0 and every 12 weeks thereafter with early escape (addition of MTX) and dose regimen adjustment (addition of MTX or switch to 4mg/kg IV golimumab), depending on joint assessment results, at Week 16 and 24, respectively. The duration of the combined IV treatment period (initial treatment plus early escape and/or dose regimen adjustment) will be a minimum of 48 weeks. The IV treatment period will be followed by the option of SC injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition, patients will receive placebo (sham MTX) capsules
IV infusions of 4mg/kg golimumab at Week 0 and every 12 weeks thereafter for a minimum of 48 weeks followed by the option of SC injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition, patients will receive MTX at the same dose as that before study entry.
IV infusions of 4mg/kg golimumab at Week 0 and every 12 weeks thereafter with early escape (addition of MTX) and dose regimen adjustment (addition of MTX), depending on joint assessment results, at Week 16 and 24, respectively. The duration of the combined IV treatment period (initial treatment plus early escape and/or dose regimen adjustment) will be a minimum of 48 weeks. The IV treatment period will be followed by the option of SC injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition, patients will receive placebo (sham MTX) capsules.
IV infusions of placebo at Week 0 and Week 12 with early escape (switch to 4mg/kg IV golimumab) and dose regimen adjustment (switch to 4mg/kg IV golimumab), depending on joint assessment results, at Week 16 and 24, respectively. The duration of the combined IV treatment period (placebo plus golimumab) will be a minimum of 48 weeks. The IV treatment period will be followed by the option of SC injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition patients will receive MTX at the same dose as that before study entry. Participants still receiving placebo injections at Week 48 are not eligible to enter the Extension Study.
Outcomes
Primary Outcome Measures
Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 14
An ACR 50 response is defined as a greater than or equal to 50 percentage improvement from baseline in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) 2. greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: a. Patient's assessment of pain (VAS) (0-10 cm) b. Patient's Global Assessment of Disease activity (VAS) (0-10 cm) c. Physician's Global Assessment of Disease Activity (VAS) (0-10 cm) d. Patient's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein (CRP).
Secondary Outcome Measures
Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24
ACR 50 response is an improvement of greater than or equal to 50 percentage from baseline in both the tender and swollen joint count and in at least 3 of the 5 assessments (patient's assessment of pain, patient's global assessemnt of disease activity, Physician's global assessment of disease activity (based on a scale of 0=no disease to 10=severe disease), HAQ (20 questions on life activities) and CRP blood test to measure inflammation).
Number of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14
ACR 20 response is an improvement of greater than or equal to 20 percentage from baseline in both the tender and swollen joint count and in at least 3 of the 5 assessments (patient's assessment of pain, patient's global assessemnt of disease activity, Physician's global assessment of disease activity [based on a scale of 0=no disease to 10=severe disease), HAQ (20 questions on life activities] and CRP blood test to measure inflammation).
Number of Participants With a Disease Activity Index Score 28 (Using C-reactive Protein)Moderate or Good Response at Week 14
DAS28 using CRP is a measure of tender and swollen joints (28 joints each) and the patient's assessment of disease activity. Values range from 0 (best) to 10 (worst). A score of higher than 5.1 indicates high disease activity, and a score below 3.2 indicates low disease activity. A "Good" response is defined as a patient with a DAS28 score of <= 3.2 at Week 14 with improvement from Baseline in DAS28 score of > 1.2. A "Moderate" response is defined as a patient with DAS28 score of >3.2-5.1 at Week 14 with improvement from baseline in DAS28 score of >1.2 or a DAS28 score of <= 5.1 and improvement from baseline in DAS28 score of >0.6 to 1.2
Physical Component Summary (PCS) Score of the Short Form-36 (SF-36) at Week 14
The SF-36 consists of 8 multi-item scales: limitations in physical functioning due to health problems, usual role activities due to physical health problems, bodily pain, usual role activities due to personal or emotional problems, social functioning due to physical or mental health problems, general mental health (psychological distress and well-being), vitality and general health perception. The values are 100=best to 0=worst.
Full Information
NCT ID
NCT00361335
First Posted
August 4, 2006
Last Updated
July 23, 2014
Sponsor
Centocor, Inc.
Collaborators
Schering-Plough
1. Study Identification
Unique Protocol Identification Number
NCT00361335
Brief Title
A Study of Safety and Effectiveness of Golimumab in Participants With Active Rheumatoid Arthritis Despite Methotrexate Therapy
Official Title
A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, a Fully Human Anti-TNFa Monoclonal Antibody, Administered Intravenously, in Subjects With Active Rheumatoid Arthritis Despite Methotrexate Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
December 2007 (Actual)
Study Completion Date
September 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centocor, Inc.
Collaborators
Schering-Plough
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to assess the clinical effectiveness and safety of golimumab intravenous (IV) infusions every 12 weeks with or without Methotrexate (MTX), compared with MTX alone, in patients with active rheumatoid arthritis (RA) despite concurrent MTX treatment. In addition, the safety of subcutaneous (SC) golimumab injections following transition from IV golimumab infusions will also be evaluated.
Detailed Description
This is a Phase III, double blind (neither investigator nor participant knows the treatment received), placebo-controlled (an inactive substance that is compared with the study medication to test whether the study medication has a real effect in clinical study), multicenter, 5-arm (treatment groups) study of golimumab at 2 doses (given with or without MTX over a period of 30 minutes) for at least 48 weeks in patients with active RA despite concurrent MTX therapy. The study consists of a treatment period of golimumab IV infusions (IV Period) which ranges from 48 weeks to approximately 140 weeks, assuming an enrollment period of approximately 92 weeks, and a long-term optional extension period (Extension Study) in which golimumab SC injections will be given for 24 weeks. The end of study will be the time the last participant completes the Week E-40 visit (Extension Study) for safety follow-up assessments. For the IV Period, participants will be randomly assigned to 1 of the 5 treatment groups in a 1:1:1:1:1 ratio (approximately 125 patients per group). At Week 16 and Week 24, joint assessment results will be used to allow participants to enter early escape and dose regimen adjustment, respectively, in a blinded fashion. Treatment will be unblinded after the 48-week database lock and participants will be given the option to participate in the Extension Study and receive SC injections of 50mg golimumab (with or without MTX) every 4 weeks for an additional 24 weeks. Safety will be monitored throughout the study. The entire study duration (IV Period plus Extension Study) for each participant will range from 88 weeks up to 192 weeks, assuming an enrollment period of approximately 92 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid arthritis, Golimumab, Methotrexate, Tumor Necrosis Factor-alpha, Immunology
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
643 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group I: 2mg/kg Golimumab + MTX
Arm Type
Experimental
Arm Description
Intravenous (IV) infusions of 2mg/kg golimumab at Week 0 and every 12 weeks thereafter with early escape (an additional 2mg/kg IV infusion of golimumab) and dose regimen adjustment (switch to 4mg/kg IV golimumab), depending on joint assessment results, at Week 16 and 24, respectively. The duration of the combined IV treatment period (initial treatment plus early escape and/or dose regimen adjustment) will be a minimum of 48 weeks. The IV treatment period will be followed by the option of subcutaneous (SC) injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition, patients will receive methotrexate (MTX) at the same dose as that before study entry
Arm Title
Group II: 2mg/kg Golimumab only
Arm Type
Experimental
Arm Description
IV infusions of 2mg/kg golimumab at Week 0 and every 12 weeks thereafter with early escape (addition of MTX) and dose regimen adjustment (addition of MTX or switch to 4mg/kg IV golimumab), depending on joint assessment results, at Week 16 and 24, respectively. The duration of the combined IV treatment period (initial treatment plus early escape and/or dose regimen adjustment) will be a minimum of 48 weeks. The IV treatment period will be followed by the option of SC injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition, patients will receive placebo (sham MTX) capsules
Arm Title
Group III: 4mg/kg Golimumab + MTX
Arm Type
Experimental
Arm Description
IV infusions of 4mg/kg golimumab at Week 0 and every 12 weeks thereafter for a minimum of 48 weeks followed by the option of SC injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition, patients will receive MTX at the same dose as that before study entry.
Arm Title
Group IV: 4mg/kg Golimumab only
Arm Type
Experimental
Arm Description
IV infusions of 4mg/kg golimumab at Week 0 and every 12 weeks thereafter with early escape (addition of MTX) and dose regimen adjustment (addition of MTX), depending on joint assessment results, at Week 16 and 24, respectively. The duration of the combined IV treatment period (initial treatment plus early escape and/or dose regimen adjustment) will be a minimum of 48 weeks. The IV treatment period will be followed by the option of SC injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition, patients will receive placebo (sham MTX) capsules.
Arm Title
Group V: IV Placebo + MTX
Arm Type
Placebo Comparator
Arm Description
IV infusions of placebo at Week 0 and Week 12 with early escape (switch to 4mg/kg IV golimumab) and dose regimen adjustment (switch to 4mg/kg IV golimumab), depending on joint assessment results, at Week 16 and 24, respectively. The duration of the combined IV treatment period (placebo plus golimumab) will be a minimum of 48 weeks. The IV treatment period will be followed by the option of SC injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition patients will receive MTX at the same dose as that before study entry. Participants still receiving placebo injections at Week 48 are not eligible to enter the Extension Study.
Intervention Type
Drug
Intervention Name(s)
Golimumab
Intervention Description
2mg/kg or 4mg/kg will be administered as an IV infusion over 30 minutes
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
Active MTX capsules, filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg MTX tablet, will be administered at the same dose as before the study entry.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
sham MTX
Intervention Description
Placebo solution will be administered through IV infusion in Group V and oral placebo capsules (sham MTX) filled with microcrystalline cellulose (Avicel PH 102) will be administered in Group II and IV.
Primary Outcome Measure Information:
Title
Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 14
Description
An ACR 50 response is defined as a greater than or equal to 50 percentage improvement from baseline in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) 2. greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: a. Patient's assessment of pain (VAS) (0-10 cm) b. Patient's Global Assessment of Disease activity (VAS) (0-10 cm) c. Physician's Global Assessment of Disease Activity (VAS) (0-10 cm) d. Patient's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein (CRP).
Time Frame
Week 0 to Week 14
Secondary Outcome Measure Information:
Title
Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24
Description
ACR 50 response is an improvement of greater than or equal to 50 percentage from baseline in both the tender and swollen joint count and in at least 3 of the 5 assessments (patient's assessment of pain, patient's global assessemnt of disease activity, Physician's global assessment of disease activity (based on a scale of 0=no disease to 10=severe disease), HAQ (20 questions on life activities) and CRP blood test to measure inflammation).
Time Frame
Week 0 to Week 24
Title
Number of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14
Description
ACR 20 response is an improvement of greater than or equal to 20 percentage from baseline in both the tender and swollen joint count and in at least 3 of the 5 assessments (patient's assessment of pain, patient's global assessemnt of disease activity, Physician's global assessment of disease activity [based on a scale of 0=no disease to 10=severe disease), HAQ (20 questions on life activities] and CRP blood test to measure inflammation).
Time Frame
Week 0 to Week 14
Title
Number of Participants With a Disease Activity Index Score 28 (Using C-reactive Protein)Moderate or Good Response at Week 14
Description
DAS28 using CRP is a measure of tender and swollen joints (28 joints each) and the patient's assessment of disease activity. Values range from 0 (best) to 10 (worst). A score of higher than 5.1 indicates high disease activity, and a score below 3.2 indicates low disease activity. A "Good" response is defined as a patient with a DAS28 score of <= 3.2 at Week 14 with improvement from Baseline in DAS28 score of > 1.2. A "Moderate" response is defined as a patient with DAS28 score of >3.2-5.1 at Week 14 with improvement from baseline in DAS28 score of >1.2 or a DAS28 score of <= 5.1 and improvement from baseline in DAS28 score of >0.6 to 1.2
Time Frame
Week 0 to Week 14
Title
Physical Component Summary (PCS) Score of the Short Form-36 (SF-36) at Week 14
Description
The SF-36 consists of 8 multi-item scales: limitations in physical functioning due to health problems, usual role activities due to physical health problems, bodily pain, usual role activities due to personal or emotional problems, social functioning due to physical or mental health problems, general mental health (psychological distress and well-being), vitality and general health perception. The values are 100=best to 0=worst.
Time Frame
Weeks 0 to Week 14
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
- Must have a diagnosis of active rheumatoid arthritis (RA) (according to the revised 1987 criteria of the ARA (American Rheumatism Association) with at least 4 swollen and 4 tender joints for at least 3 months prior to screening - Have been treated with and tolerated methotrexate (MTX) at a dose of at least 15 mg per week for at least 3 months prior to screening - Have been on a stable MTX dose of greater than or equal to 15 mg per week and less than or eual to 25 mg per week for at least 4 weeks prior to screening - If using non steroidal anti-inflammatory agents (such as naproxen) or other pain relievers for RA, must be on a stable dose for at least 2 weeks prior to the first administration of study agent
Exclusion Criteria:
- Participants having known hypersensitivity (severe allergy) to human immunoglobulin proteins or other components of golimumab - Having known clinically serious adverse reaction to a biologic anti-TNF agent - Have had history of latent or active granulomatous infection, including tuberculosis, histoplasmosis, or coccidioidomycosis, prior to screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Centocor, Inc. Clinical Trial
Organizational Affiliation
Centocor, Inc.
Official's Role
Study Director
Facility Information:
City
Peoria
State/Province
Arizona
Country
United States
City
Aventura
State/Province
Florida
Country
United States
City
Orlando
State/Province
Florida
Country
United States
City
Tampa
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Lincoln
State/Province
Nebraska
Country
United States
City
Omaha
State/Province
Nebraska
Country
United States
City
Voorhees
State/Province
New Jersey
Country
United States
City
Albany
State/Province
New York
Country
United States
City
Roslyn
State/Province
New York
Country
United States
City
Charlotte
State/Province
North Carolina
Country
United States
City
Oklahoma City
State/Province
Oklahoma
Country
United States
City
Duncansville
State/Province
Pennsylvania
Country
United States
City
Norristown
State/Province
Pennsylvania
Country
United States
City
West Reading
State/Province
Pennsylvania
Country
United States
City
Willow Grove
State/Province
Pennsylvania
Country
United States
City
Amarillo
State/Province
Texas
Country
United States
City
Fort Worth
State/Province
Texas
Country
United States
City
Lubbock
State/Province
Texas
Country
United States
City
Spokane
State/Province
Washington
Country
United States
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
Fitzroy
Country
Australia
City
Heidelberg
Country
Australia
City
Maroochydore
Country
Australia
City
Melbourne
Country
Australia
City
Perth
Country
Australia
City
Woodville
Country
Australia
City
Barranquilla
Country
Colombia
City
Bogota
Country
Colombia
City
Bucaramanga
Country
Colombia
City
Floridablanca
Country
Colombia
City
Erlangen
Country
Germany
City
Hamburg
Country
Germany
City
Magdeburg
Country
Germany
City
München
Country
Germany
City
Budapest
Country
Hungary
City
Szolnok
Country
Hungary
City
Daugavpils
Country
Latvia
City
Riga
Country
Latvia
City
Kaunas
Country
Lithuania
City
Klaipeda
Country
Lithuania
City
Siauliai
Country
Lithuania
City
Vilnius
Country
Lithuania
City
Ipoh
Country
Malaysia
City
Kuching
Country
Malaysia
City
Precinct 7
Country
Malaysia
City
Selangor Darul Ehasan
Country
Malaysia
City
Msd06 Gwardiamangia
Country
Malta
City
Col. Del Valle
Country
Mexico
City
Guadalajara Jalisco
Country
Mexico
City
Guadalajara N/A
Country
Mexico
City
Monterrey
Country
Mexico
City
Christchurch
Country
New Zealand
City
Dunedin
Country
New Zealand
City
Rotorua
Country
New Zealand
City
Takapuna Auckland
Country
New Zealand
City
Timaru
Country
New Zealand
City
Lima
Country
Peru
City
Bialystok
Country
Poland
City
Elblag
Country
Poland
City
Krakow
Country
Poland
City
Warszawa
Country
Poland
City
Wloszczowa
Country
Poland
City
Kiev
Country
Ukraine
City
Kyiv
Country
Ukraine
City
Symferpol
Country
Ukraine
City
Zhaporizhzhya
Country
Ukraine
12. IPD Sharing Statement
Citations:
PubMed Identifier
28606966
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.
Results Reference
derived
PubMed Identifier
24757132
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.
Results Reference
derived
PubMed Identifier
22776409
Citation
Baker JF, Baker DG, Toedter G, Shults J, Von Feldt JM, Leonard MB. Associations between vitamin D, disease activity, and clinical response to therapy in rheumatoid arthritis. Clin Exp Rheumatol. 2012 Sep-Oct;30(5):658-64. Epub 2012 Oct 17.
Results Reference
derived
PubMed Identifier
22089463
Citation
Taylor PC, Ritchlin C, Mendelsohn A, Baker D, Kim L, Xu Z, Mack M, Kremer J. Maintenance of efficacy and safety with subcutaneous golimumab among patients with active rheumatoid arthritis who previously received intravenous golimumab. J Rheumatol. 2011 Dec;38(12):2572-80. doi: 10.3899/jrheum.110570. Epub 2011 Nov 15.
Results Reference
derived
PubMed Identifier
20131276
Citation
Kremer J, Ritchlin C, Mendelsohn A, Baker D, Kim L, Xu Z, Han J, Taylor P. Golimumab, a new human anti-tumor necrosis factor alpha antibody, administered intravenously in patients with active rheumatoid arthritis: Forty-eight-week efficacy and safety results of a phase III randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2010 Apr;62(4):917-28. doi: 10.1002/art.27348. Erratum In: Arthritis Rheum. 2010 Oct;62(10):3130.
Results Reference
derived
Learn more about this trial
A Study of Safety and Effectiveness of Golimumab in Participants With Active Rheumatoid Arthritis Despite Methotrexate Therapy
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