Clinical trial NCT00361335: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid arthritis
Golimumab
Methotrexate
Tumor Necrosis Factor-alpha
Immunology
Lead sponsor: Centocor, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Schering-Plough
First posted: 2006-08-08
Enrollment: 643
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 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.

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

Primary outcomes:
measure: Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 14
timeFrame: Week 0 to Week 14
Secondary outcomes:
measure: Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24
timeFrame: Week 0 to Week 24
measure: Number of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14
timeFrame: Week 0 to Week 14
measure: Number of Participants With a Disease Activity Index Score 28 (Using C-reactive Protein)Moderate or Good Response at Week 14
timeFrame: Week 0 to Week 14
measure: Physical Component Summary (PCS) Score of the Short Form-36 (SF-36) at Week 14
timeFrame: Weeks 0 to Week 14
Other outcomes:
Locations:
city: Peoria
country: United States
state: Arizona
city: Aventura
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Lincoln
country: United States
state: Nebraska
city: Omaha
country: United States
state: Nebraska
city: Voorhees
country: United States
state: New Jersey
city: Albany
country: United States
state: New York
city: Roslyn
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Oklahoma City
country: United States
state: Oklahoma
city: Duncansville
country: United States
state: Pennsylvania
city: Norristown
country: United States
state: Pennsylvania
city: West Reading
country: United States
state: Pennsylvania
city: Willow Grove
country: United States
state: Pennsylvania
city: Amarillo
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Lubbock
country: United States
state: Texas
city: Spokane
country: United States
state: Washington
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
Study officials:
affiliation: Centocor, Inc.
name: Centocor, Inc. Clinical Trial
role: STUDY_DIRECTOR
References:
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: 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: 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.
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.
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.