An Effectiveness and Safety Study of Intravenous Golimumab in Patients With Active Rheumatoid Arthritis Despite Treatment With Methotrexate Therapy

November 29, 2013 updated by: Centocor, Inc.

A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, an Anti-TNFalpha Monoclonal Antibody, Administered Intravenously, in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy

The purpose of this study is to evaluate clinical effectiveness and safety of golimumab with methotrexate (MTX) in the treatment of rheumatoid arthritis (RA) when compared to MTX alone.

Study Overview

Detailed Description

This is a randomized (study medication is assigned by chance), double-blind (neither physician nor participants knows the treatment that the participant receives), placebo-controlled (an inactive substance is compared with a medication to test whether the medication has a real effect in a clinical study), multicenter, 2-arm (2 groups) study of golimumab in participants with active RA despite concurrent MTX therapy. Approximately 564 participants will be randomly allocated to 1 of 2 treatment groups in a 2:1 ratio ie, Group 1(approximately 376 participants will receive golimumab + MTX) and Group 2 (approximately 188 participants will receive MTX + placebo). Total duration of study for each participant is 112 weeks. Safety will be evaluated by assessment of adverse events, tuberculosis testing and blood testing.

Study Type

Interventional

Enrollment (Actual)

592

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
      • Buenos Aires N/A, Argentina
      • Cordoba, Argentina
      • Rosario, Argentina
      • San Juan, Argentina
      • San Miguel De Tucuman, Argentina
      • Santa Fe, Argentina
      • Cairns, Australia
      • Maroochydore, Australia
      • Melbourne, Australia
      • Woodville, Australia
      • Woolloongabba, Australia
      • Antioquia, Colombia
      • Barranquilla, Colombia
      • Bogota, Colombia
      • Cali Valley Del Cauca, Colombia
      • Medellin, Colombia
      • Budapest, Hungary
      • Debrecen, Hungary
      • Eger, Hungary
      • Gyor, Hungary
      • Gyula, Hungary
      • Szombathely, Hungary
      • Veszprem, Hungary
      • Anyang, Korea, Republic of
      • Dae-Gu, Korea, Republic of
      • Daejeon, Korea, Republic of
      • Incheon, Korea, Republic of
      • Pusan, Korea, Republic of
      • Seoul, Korea, Republic of
      • Alytus, Lithuania
      • Kaunas, Lithuania
      • Klaipeda, Lithuania
      • Siauliai, Lithuania
      • Vilnius, Lithuania
      • Georgetown, Malaysia
      • Ipoh, Malaysia
      • Johor Bahru, Malaysia
      • Kota Kinabalu, Malaysia
      • Kuantan, Malaysia
      • Kuching, Malaysia
      • Precinct 7, Malaysia
      • Selangor Darul Ehasan, Malaysia
      • Seremban, Malaysia
      • Guadalajara, Mexico
      • Leon, Mexico
      • Mex, Mexico
      • Mexico, Mexico
      • Monterrey, Mexico
      • Auckland, New Zealand
      • Takapuna Auckland, New Zealand
      • Timaru, New Zealand
      • Bialystok, Poland
      • Bydgoszcz, Poland
      • Dzialdowo, Poland
      • Elblag, Poland
      • Katowice, Poland
      • Lublin, Poland
      • Poznan, Poland
      • Sopot, Poland
      • Szczecin, Poland
      • Warszawa, Poland
      • Wloszczowa, Poland
      • Wrocław, Poland
      • Chelyabinsk, Russian Federation
      • Ekaterinburg, Russian Federation
      • Krasnoyarsk, Russian Federation
      • Moscow, Russian Federation
      • Moscow N/A, Russian Federation
      • Petrozavodsk, Russian Federation
      • Saint Petersburg, Russian Federation
      • Saratov, Russian Federation
      • St.Petersburg, Russian Federation
      • Donetsk, Ukraine
      • Ivano-Frankovsk, Ukraine
      • Kharkiv, Ukraine
      • Kyiv, Ukraine
      • Odessa, Ukraine
      • Simferopol, Ukraine
      • Ternopil, Ukraine
      • Vinnitsa, Ukraine
      • Zaporizhzhya, Ukraine
    • Florida
      • Daytona Beach, Florida, United States
      • Miami, Florida, United States
      • Palm Harbor, Florida, United States
    • Illinois
      • Moline, Illinois, United States
    • Maryland
      • Wheaton, Maryland, United States
    • Massachusetts
      • Worcester, Massachusetts, United States
    • Nebraska
      • Lincoln, Nebraska, United States
    • Ohio
      • Cincinnati, Ohio, United States
    • Texas
      • Lubbock, Texas, 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:

  • Diagnosis of rheumatoid arthritis (RA) for at least 3 months prior to screening
  • Have been treated with and tolerated methotrexate (MTX) at a dose of at least 15 mg/week for at least 3 months prior to screening, and have been on a stable MTX dose of 15 mg/week to 25 mg/week for at least 4 weeks prior to screening
  • Have an active RA, as defined by disease activity with at least 6 swollen and 6 tender joints, at the time of screening and at baseline
  • C-Reactive Protein greater than or equal to 1.0 mg/dL at screening
  • No history of latent or active tuberculosis prior to screening

Exclusion Criteria:

  • Other inflammatory diseases, including but not limited to psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, or lyme disease
  • Treated with disease modifying agents (other than methotrexate)/systemic immunosuppressives (eg, D-penicillamine, hydroxychloroquine, chloroquine, oral or parenteral gold, sulfasalazine, leflunomide, azathioprine, cyclosporine, mycophenolate mofetil) during the 4 weeks prior to first administration of study agent
  • Received intra-articular (in the joint), intramuscular (in the muscle), or intravenous corticosteroids, including adrenocorticotropic hormone, during the 4 weeks prior to first administration of study agent
  • Known allergy to human immunoglobulin proteins or other components of golimumab
  • Received any commercial or investigational anti-tumor necrosis factor alpha therapy such as but not exclusively infliximab, golimumab, adalimumab or etanercept

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: Placebo + Methotrexate (MTX)
Participants will receive placebo at Weeks 0, 4, 12, and 16. Participants will cross over to golimumab at Week 24, and receive administrations at Weeks 24, 28, and every 8 weeks thereafter. They will be maintained on their stable dose of commercial methotrexate throughout the study. Participants will be eligible for early escape (receive golimumab) at Week 16 if they demonstrate a less than 10 percent improvement in both tender and swollen joint count. These participants will receive golimumab at Weeks 16, 20, and every 8 weeks thereafter.
Participants will receive 2 mg/kg of golimumab intravenously over 30 ± 10 minutes. Group 1: at Weeks 0, 4, and every 8 weeks thereafter (up to Week 100). Group II: Weeks 24, 28, and every 8 weeks thereafter (up to Week 100); Early escape: at Week 16, 20 and every 8 weeks thereafter (up to Week 100).
Participants will receive placebo intravenous infusion over 30 ± 10 minutes as: Group I: at Week 16 and 24; Group II: at Weeks 0, 4, 12, 16, and 20; and for early escape: at Week 24.
Participants will be maintained on their stable dose of commercial MTX (between 15 to 25 mg/week) throughout the study.
Placebo Comparator: Group II: Golimumab + Methotrexate (MTX)
Participants will receive golimumab at Weeks 0, 4, and every 8 weeks thereafter. They will be maintained on their stable dose of commercial methotrexate throughout the study. Participants will receive a placebo infusion at Week 16 and Week 24 to maintain the blind.
Participants will receive 2 mg/kg of golimumab intravenously over 30 ± 10 minutes. Group 1: at Weeks 0, 4, and every 8 weeks thereafter (up to Week 100). Group II: Weeks 24, 28, and every 8 weeks thereafter (up to Week 100); Early escape: at Week 16, 20 and every 8 weeks thereafter (up to Week 100).
Participants will receive placebo intravenous infusion over 30 ± 10 minutes as: Group I: at Week 16 and 24; Group II: at Weeks 0, 4, 12, 16, and 20; and for early escape: at Week 24.
Participants will be maintained on their stable dose of commercial MTX (between 15 to 25 mg/week) throughout the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14
Time Frame: Week 14
An ACR 20 response is defined as a greater than or equal to 20 percent improvement from baseline in: 1. Swollen (66 joints) and tender (68 joints) joint counts; 2. greater than or equal to 20 percentage improvement in at least 3 of the following 5 assessments: a. Participant's assessment of pain by Visual Analog Scale (VAS), (0 [no pain] to 10 [worst pain]) b. Participant's global assessment of disease activity by VAS c. Physician's global assessment of disease activity by VAS d. Participant's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C-reactive protein.
Week 14

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Participants With Moderate or Good Response in Disease Activity Index Score 28 (DAS28) Using C-reactive Protein (CRP) at Week 14
Time Frame: Week 14
DAS28 using CRP is an index to measure the disease activity in participants with rheumatoid arthritis combining tender joints (28 joints), swollen joints (28 joints), CRP, and participant's global assessment of disease activity. The DAS28 score ranges from 0 (best) to 10 (worst). DAS28 score above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Higher scores indicate worsening. A decrease in DAS28 score >1.2 is being referred to as a "good response" and a decrease of 0.6-1.2 as a "moderate response".
Week 14
Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Week 14
Time Frame: Week 14
The HAQ is 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 (no difficulty), to 3 (inability to perform a task in that area). HAQscore on a scale ranges from 0 (no disability) to 3 (completely disabled). Higher scores indicate worsening.
Week 14
Proportion of Participants Who Achieved American College of Rheumatology (ACR) 50 Response at Week 24
Time Frame: Week 24
An ACR 50 response is defined as a greater than or equal to 50 percent improvement from baseline in: 1. Swollen (66 joints) and tender (68 joints) joint counts; 2. greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: a. Participant's assessment of pain by Visual Analog Scale (VAS) (0-10 cm) b. Participant's global assessment of disease activity by VAS (0-10 cm) c. Physician's global assessment of disease activity by VAS (0-10 cm) d. Participant's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein.
Week 24
Change From Baseline in Total Van Der Heijde Modified Sharp (vdH-S) Score at Week 24.
Time Frame: Week 24
Total vdH-S score is sum of joint erosion score and joint-space narrowing (JSN) score. Joint erosion score summarizes erosion severity in 32 joints of hands and 12 joints of feet. Each joint scored from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Maximal erosion score is 280. JSN score summarizes severity of JSN in 30 joints of hands and 12 joints of feet. Assessment of JSN, including subluxation, is scored from 0 (normal) to 4 (bony ankylosis or complete luxation). Maximal JSN score is 168. Thus, the worst possible vdH-S score is 448.
Week 24

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, 2009

Primary Completion (Actual)

March 1, 2011

Study Completion (Actual)

February 1, 2013

Study Registration Dates

First Submitted

September 4, 2009

First Submitted That Met QC Criteria

September 4, 2009

First Posted (Estimate)

September 9, 2009

Study Record Updates

Last Update Posted (Estimate)

December 25, 2013

Last Update Submitted That Met QC Criteria

November 29, 2013

Last Verified

November 1, 2013

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.

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