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

NCT ID: NCT00361335

Last Updated: 2014-07-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 643 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2009-09-30

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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group I: 2mg/kg Golimumab + MTX

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

Group Type: EXPERIMENTAL

Golimumab

Intervention Type: DRUG

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

Methotrexate

Intervention Type: 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 II: 2mg/kg Golimumab only

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

Group Type: EXPERIMENTAL

Golimumab

Intervention Type: DRUG

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

Placebo

Intervention Type: 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.

Group III: 4mg/kg Golimumab + MTX

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.

Group Type: EXPERIMENTAL

Golimumab

Intervention Type: DRUG

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

Methotrexate

Intervention Type: 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 IV: 4mg/kg Golimumab only

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.

Group Type: EXPERIMENTAL

Golimumab

Intervention Type: DRUG

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

Placebo

Intervention Type: 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.

Group V: IV Placebo + MTX

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.

Group Type: PLACEBO_COMPARATOR

Methotrexate

Intervention Type: 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.

Placebo

Intervention Type: 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.

Interventions

Golimumab

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

Intervention Type: DRUG

Methotrexate

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

Placebo

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.

Intervention Type: DRUG

Other Intervention Names

sham MTX

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Schering-Plough

INDUSTRY

Sponsor Role: collaborator

Centocor, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Centocor, Inc. Clinical Trial

Role: STUDY_DIRECTOR

Centocor, Inc.

Locations

Peoria, Arizona, United States

Aventura, Florida, United States

Orlando, Florida, United States

Tampa, Florida, United States

Atlanta, Georgia, United States

Lincoln, Nebraska, United States

Omaha, Nebraska, United States

Voorhees Township, New Jersey, United States

Albany, New York, United States

Roslyn, New York, United States

Charlotte, North Carolina, United States

Oklahoma City, Oklahoma, United States

Duncansville, Pennsylvania, United States

Norristown, Pennsylvania, United States

West Reading, Pennsylvania, United States

Willow Grove, Pennsylvania, United States

Amarillo, Texas, United States

Fort Worth, Texas, United States

Lubbock, Texas, United States

Spokane, Washington, United States

Buenos Aires, , Argentina

Córdoba, , Argentina

Rosario, , Argentina

San Juan, , Argentina

San Miguel de Tucumán, , Argentina

Santa Fe, , Argentina

Fitzroy, , Australia

Heidelberg, , Australia

Maroochydore, , Australia

Melbourne, , Australia

Perth, , Australia

Woodville, , Australia

Barranquilla, , Colombia

Bogotá, , Colombia

Bucaramanga, , Colombia

Floridablanca, , Colombia

Erlangen, , Germany

Hamburg, , Germany

Magdeburg, , Germany

München, , Germany

Budapest, , Hungary

Szolnok, , Hungary

Daugavpils, , Latvia

Riga, , Latvia

Kaunas, , Lithuania

Klaipėda, , Lithuania

Šiauliai, , Lithuania

Vilnius, , Lithuania

Ipoh, , Malaysia

Kuching, , Malaysia

Precinct 7, , Malaysia

Selangor Darul Ehasan, , Malaysia

Msd06 Gwardiamangia, , Malta

Colonia del Valle, , Mexico

Guadalajara, , Mexico

Guadalajara Jalisco, , Mexico

Monterrey, , Mexico

Christchurch, , New Zealand

Dunedin, , New Zealand

Rotorua, , New Zealand

Takapuna Auckland, , New Zealand

Timaru, , New Zealand

Lima, , Peru

Bialystok, , Poland

Elblag, , Poland

Krakow, , Poland

Warsaw, , Poland

Włoszczowa, , Poland

Kiev, , Ukraine

Kyiv, , Ukraine

Symferpol, , Ukraine

Zhaporizhzhya, , Ukraine

Countries

United States; Argentina; Australia; Colombia; Germany; Hungary; Latvia; Lithuania; Malaysia; Malta; Mexico; New Zealand; Peru; Poland; Ukraine

References

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.

Reference Type: DERIVED

PMID: 28606966 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24757132 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22776409 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22089463 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 20131276 (View on PubMed)

Other Identifiers

C0524T12

Identifier Type: OTHER

Identifier Source: secondary_id

2005-003232-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR012781

Identifier Type: -

Identifier Source: org_study_id