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

July 23, 2014 updated by: Centocor, Inc.

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

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.

Study Overview

Status

Completed

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.

Study Type

Interventional

Enrollment (Actual)

643

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Buenos Aires, Argentina
      • Cordoba, Argentina
      • Rosario, Argentina
      • San Juan, Argentina
      • San Miguel De Tucuman, Argentina
      • Santa Fe, Argentina
      • Fitzroy, Australia
      • Heidelberg, Australia
      • Maroochydore, Australia
      • Melbourne, Australia
      • Perth, Australia
      • Woodville, Australia
      • Barranquilla, Colombia
      • Bogota, Colombia
      • Bucaramanga, Colombia
      • Floridablanca, Colombia
      • Erlangen, Germany
      • Hamburg, Germany
      • Magdeburg, Germany
      • München, Germany
      • Budapest, Hungary
      • Szolnok, Hungary
      • Daugavpils, Latvia
      • Riga, Latvia
      • Kaunas, Lithuania
      • Klaipeda, Lithuania
      • Siauliai, Lithuania
      • Vilnius, Lithuania
      • Ipoh, Malaysia
      • Kuching, Malaysia
      • Precinct 7, Malaysia
      • Selangor Darul Ehasan, Malaysia
      • Msd06 Gwardiamangia, Malta
      • Col. Del Valle, Mexico
      • Guadalajara Jalisco, Mexico
      • Guadalajara N/A, 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
      • Warszawa, Poland
      • Wloszczowa, Poland
      • Kiev, Ukraine
      • Kyiv, Ukraine
      • Symferpol, Ukraine
      • Zhaporizhzhya, Ukraine
    • Arizona
      • Peoria, Arizona, United States
    • Florida
      • Aventura, Florida, United States
      • Orlando, Florida, United States
      • Tampa, Florida, United States
    • Georgia
      • Atlanta, Georgia, United States
    • Nebraska
      • Lincoln, Nebraska, United States
      • Omaha, Nebraska, United States
    • New Jersey
      • Voorhees, New Jersey, United States
    • New York
      • Albany, New York, United States
      • Roslyn, New York, United States
    • North Carolina
      • Charlotte, North Carolina, United States
    • Oklahoma
      • Oklahoma City, Oklahoma, United States
    • Pennsylvania
      • Duncansville, Pennsylvania, United States
      • Norristown, Pennsylvania, United States
      • West Reading, Pennsylvania, United States
      • Willow Grove, Pennsylvania, United States
    • Texas
      • Amarillo, Texas, United States
      • Fort Worth, Texas, United States
      • Lubbock, Texas, United States
    • Washington
      • Spokane, Washington, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
2mg/kg or 4mg/kg will be administered as an IV infusion over 30 minutes
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.
Experimental: 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
2mg/kg or 4mg/kg will be administered as an IV infusion over 30 minutes
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.
Other Names:
  • sham MTX
Experimental: 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.
2mg/kg or 4mg/kg will be administered as an IV infusion over 30 minutes
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.
Experimental: 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.
2mg/kg or 4mg/kg will be administered as an IV infusion over 30 minutes
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.
Other Names:
  • sham MTX
Placebo Comparator: 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.
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 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.
Other Names:
  • sham MTX

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 14
Time Frame: Week 0 to 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24
Time Frame: Week 0 to 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).
Week 0 to Week 24
Number of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14
Time Frame: Week 0 to 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).
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
Time Frame: Week 0 to 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
Week 0 to Week 14
Physical Component Summary (PCS) Score of the Short Form-36 (SF-36) at Week 14
Time Frame: Weeks 0 to 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.
Weeks 0 to Week 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Collaborators

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (Actual)

December 1, 2007

Study Completion (Actual)

September 1, 2009

Study Registration Dates

First Submitted

August 4, 2006

First Submitted That Met QC Criteria

August 4, 2006

First Posted (Estimate)

August 8, 2006

Study Record Updates

Last Update Posted (Estimate)

July 29, 2014

Last Update Submitted That Met QC Criteria

July 23, 2014

Last Verified

July 1, 2014

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Rheumatoid Arthritis

Clinical Trials on Golimumab

3
Subscribe