A Study of Safety and Effectiveness of Golimumab in Participants With Active Rheumatoid Arthritis Despite Methotrexate Therapy

NCT00361335 | Completed Phase 3 Results DMC

• 3 other identifiers: CR012781C0524T122005-003232-21
• Study Type: interventional
• Target: 643
• Locations: 15 countries
• Sites: 72

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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis; Golimumab; Methotrexate; Tumor Necrosis Factor-alpha; Immunology

Outcome Measures

Primary Outcomes (1)

• 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).

  Week 0 to Week 14

Secondary Outcomes (4)

• Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24

  Week 0 to Week 24

• Number of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14

  Week 0 to Week 14

• Number of Participants With a Disease Activity Index Score 28 (Using C-reactive Protein)Moderate or Good Response at Week 14

  Week 0 to Week 14

• Physical Component Summary (PCS) Score of the Short Form-36 (SF-36) at Week 14

  Weeks 0 to Week 14

Study Arms (5)

Group I: 2mg/kg Golimumab + MTX

EXPERIMENTAL

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

Drug: Golimumab; Drug: Methotrexate

Group II: 2mg/kg Golimumab only

EXPERIMENTAL

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

Drug: Golimumab; Drug: Placebo

Group III: 4mg/kg Golimumab + MTX

EXPERIMENTAL

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.

Drug: Golimumab; Drug: Methotrexate

Group IV: 4mg/kg Golimumab only

EXPERIMENTAL

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.

Drug: Golimumab; Drug: Placebo

Group V: IV Placebo + MTX

PLACEBO COMPARATOR

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.

Drug: Methotrexate; Drug: Placebo

Interventions

Golimumab DRUG

2mg/kg or 4mg/kg will be administered as an IV infusion over 30 minutes

Group I: 2mg/kg Golimumab + MTX; Group II: 2mg/kg Golimumab only; Group III: 4mg/kg Golimumab + MTX; Group IV: 4mg/kg Golimumab only

Methotrexate DRUG

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.

Group I: 2mg/kg Golimumab + MTX; Group III: 4mg/kg Golimumab + MTX; Group V: IV Placebo + MTX

Placebo DRUG

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.

Also known as: sham MTX

Group II: 2mg/kg Golimumab only; Group IV: 4mg/kg Golimumab only; Group V: IV Placebo + MTX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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

You may not qualify if:

• \- 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

Sponsors & Collaborators

• Centocor, Inc.: lead
• Schering-Plough: collaborator

Study Sites (72)

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Peoria, Arizona, United States

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Aventura, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Lincoln, Nebraska, United States

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Omaha, Nebraska, United States

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Voorhees Township, New Jersey, United States

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Albany, New York, United States

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Roslyn, New York, United States

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Charlotte, North Carolina, United States

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Oklahoma City, Oklahoma, United States

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Duncansville, Pennsylvania, United States

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Norristown, Pennsylvania, United States

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West Reading, Pennsylvania, United States

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Willow Grove, Pennsylvania, United States

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Amarillo, Texas, United States

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Fort Worth, Texas, United States

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Lubbock, Texas, United States

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Spokane, Washington, United States

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Buenos Aires, Argentina

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Córdoba, Argentina

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Rosario, Argentina

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San Juan, Argentina

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San Miguel de Tucumán, Argentina

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Santa Fe, Argentina

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Fitzroy, Australia

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Heidelberg, Australia

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Maroochydore, Australia

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Melbourne, Australia

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Perth, Australia

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Woodville, Australia

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Barranquilla, Colombia

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Bogotá, Colombia

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Bucaramanga, Colombia

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Floridablanca, Colombia

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Erlangen, Germany

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Hamburg, Germany

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Magdeburg, Germany

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München, Germany

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Budapest, Hungary

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Szolnok, Hungary

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Daugavpils, Latvia

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Riga, Latvia

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Kaunas, Lithuania

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Klaipėda, Lithuania

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Šiauliai, Lithuania

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Vilnius, Lithuania

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Ipoh, Malaysia

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Kuching, Malaysia

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Precinct 7, Malaysia

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Selangor Darul Ehasan, Malaysia

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Msd06 Gwardiamangia, Malta

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Colonia del Valle, Mexico

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Guadalajara, Mexico

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Guadalajara Jalisco, Mexico

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Monterrey, Mexico

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Christchurch, New Zealand

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Dunedin, New Zealand

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Rotorua, New Zealand

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Takapuna Auckland, New Zealand

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Timaru, New Zealand

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Lima, Peru

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Bialystok, Poland

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Elblag, Poland

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Krakow, Poland

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Warsaw, Poland

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Włoszczowa, Poland

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Kiev, Ukraine

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Kyiv, Ukraine

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Symferpol, Ukraine

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Zhaporizhzhya, Ukraine

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Related Publications (5)

• 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.

  PMID: 28606966 DERIVED

• 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.

  PMID: 24757132 DERIVED

• 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.

  PMID: 22776409 DERIVED

• 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.

  PMID: 22089463 DERIVED

• 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.

  PMID: 20131276 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

golimumab; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

The count of patients with any nonserious adverse events (NAE) excludes patients who only had NAE that occurred in \<=5% of patients.

Results Point of Contact

• Title: Senior Director Clinical Research
• Organization: Centocor, Inc.

1-800-457-6399

Study Officials

• Centocor, Inc. Clinical Trial

  Centocor, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2006
• First Posted: August 8, 2006
• Study Start: September 1, 2006
• Primary Completion: December 1, 2007
• Study Completion: September 1, 2009
• Last Updated: July 29, 2014
• Results First Posted: August 24, 2012

Record last verified: 2014-07

Locations

LA (2); CO (4); US (20); MY (4); LI (4); UA (4); NZ (5); HU (2); PE (1); AU (6); AR (6); DE (4); MA (1); PL (5); ME (4)