A Study of the Safety and Efficacy of Golimumab (CNTO 148) in Subjects With Active Rheumatoid Arthritis Previously Treated With Biologic Anti-TNFa Agent(s)

January 27, 2014 updated by: Centocor, Inc.

A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, a Fully Human Anti-TNFa Monoclonal Antibody, Administered Subcutaneously in Subjects With Active Rheumatoid Arthritis and Previously Treated With Biologic Anti- TNFa Agent(s)

The purpose of this study is to evaluate the efficacy and safety of golimumab (CNTO 148) in subjects who have active rheumatoid arthritis and have been treated previously with at least 1 dose of a biologic anti-TNFa agent (etanercept, adalimumab or infliximab).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Golimumab is a fully human protein (antibody) which binds to tumor necrosis factor-alpha (TNFa). TNFa is increased in patients with rheumatoid arthritis (RA), and plays a major role in causing the joint pain, swelling and damage from RA. Other marketed drugs that target TNFa (anti-TNFa drugs) have been shown to be effective in reducing the symptoms, signs and joint damage of RA, but have limitations with respect to safety and ease of use. This is a randomized, double-blind, placebo-controlled trial of the efficacy and safety of a new anti-TNFa drug, golimumab, at 2 doses, injected under the skin every 4 weeks in subjects with active RA previously treated with at least 1 dose of a biologic anti-TNFa agent (etanercept, adalimumab or infliximab). Concomitant therapy with methotrexate, sulfasalazine and/or hydroxychloroquine is permitted if the subject has tolerated these medications for at least 12 weeks prior to the first administration of study drug and is on a stable dose for at least 4 weeks prior to the first administration of study agent. The study hypothesis is that golimumab will be a safe and effective treatment for RA in subjects with active RA previously treated with at least one biologic anti-TNFa agent as measured by the American College of Rheumatology (ACR) response criteria, the Disease Activity Score 28 (DAS28) responses and the change from baseline in Health Assessment Questionnaire (HAQ), without causing unacceptable significant adverse effects. The ACR response criteria were designed to assess the level of improvement in the signs and symptoms of RA. The DAS28 responses also measure improvement in the signs and symptoms of RA using the joint examination and laboratory testing. The HAQ is a series of questions that measure a subject's impairment in physical function caused by RA. Patients will receive golimumab 50 mg or 100 mg or placebo injections under the skin every 4 weeks until Week 24. After Week 24, all subjects receive golimumab 50 mg or 100 mg injections, and golimumab continues for all groups every 4 weeks for about 4 and a half more years.

Study Type

Interventional

Enrollment (Actual)

461

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

  • Australia
      • Adelaide, Australia
      • Cotton Tree, Australia
      • Melbourne, Australia
  • Austria
      • Graz, Austria
      • Lainz/Wien N/A, Austria
      • Wien, Austria
  • Canada
      • Claire, Canada
    • British Columbia
      • Victoria, British Columbia, Canada
    • Manitoba
      • Winnipeg, Manitoba, Canada
    • Newfoundland and Labrador
      • St. John'S, Newfoundland and Labrador, Canada
    • Ontario
      • Kitchener, Ontario, Canada
      • Newmarket, Ontario, Canada
      • Ottawa, Ontario, Canada
      • Toronto, Ontario, Canada
    • Quebec
      • Sainte Foy, Quebec, Canada
  • Finland
      • Helsinki, Finland
      • Hyvinkaa, Finland
      • Jyvalskyla, Finland
  • Germany
      • Baden-Baden, Germany
      • Berlin, Germany
      • Erlangen, Germany
      • Hamburg, Germany
      • Herne, Germany
      • Köln, Germany
      • München, Germany
      • Vogelsang-Gommern, Germany
      • Würzburg, Germany
  • Netherlands
      • Maastricht, Netherlands
  • New Zealand
      • Auckland, New Zealand
      • Rotorua, New Zealand
      • Timaru, New Zealand
  • Spain
      • Santander, Spain
      • Sevilla, Spain
      • Valencia, Spain
  • United Kingdom
      • Leeds, United Kingdom
      • London, United Kingdom
      • Oxford, United Kingdom
  • United States
    • Alabama
      • Birmingham, Alabama, United States
      • Huntsville, Alabama, United States
    • Arizona
      • Paradise Valley, Arizona, United States
    • California
      • La Jolla, California, United States
      • Los Angeles, California, United States
      • Santa Monica, California, United States
      • Torrance, California, United States
      • Upland, California, United States
    • Connecticut
      • Trumbull, Connecticut, United States
    • Florida
      • Aventura, Florida, United States
      • Jacksonville, Florida, United States
      • Jupiter, Florida, United States
      • Largo, Florida, United States
      • Palm Harbor, Florida, United States
      • Tamarac, Florida, United States
    • Illinois
      • Moline, Illinois, United States
      • Springfield, Illinois, United States
    • Iowa
      • Cedar Rapids, Iowa, United States
    • Kansas
      • Witchita, Kansas, United States
    • Kentucky
      • Louisville, Kentucky, United States
    • Maryland
      • Wheaton, Maryland, United States
    • Massachusetts
      • Boston, Massachusetts, United States
    • Minnesota
      • Rochester, Minnesota, United States
    • Missouri
      • Saint Louis, Missouri, United States
    • New York
      • Syracuse, New York, United States
    • North Carolina
      • Charlotte, North Carolina, United States
      • Wilmington, North Carolina, United States
    • Ohio
      • Cincinnati, Ohio, United States
      • Mayfield, Ohio, United States
    • Pennsylvania
      • Duncansville, Pennsylvania, United States
      • Pittsburgh, Pennsylvania, United States
      • West Reading, Pennsylvania, United States
    • Tennessee
      • Knoxville, Tennessee, United States
    • Texas
      • Fort Worth, Texas, United States
      • Houston, Texas, United States
      • Lubbock, Texas, United States
    • Virginia
      • Arlington, Virginia, United States
    • Washington
      • Spokane, Washington, United States
    • Wisconsin
      • Brookfield, Wisconsin, United States
      • Racine, Wisconsin, 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:

  • Patients have a diagnosis of rheumatoid arthritis (RA) (according to the revised 1987 criteria of the ACR) for at least 3 months prior to screening
  • Have active RA as defined by persistent disease activity with at least 4 swollen and 4 tender joints, at the time of screening and baseline
  • Must have been previously treated with at least one dose of etanercept, adalimumab, or infliximab
  • If currently using methotrexate, sulfasalazine and/or hydroxychloroquine must have tolerated these agents for at least 12 weeks and be on a stable dose for at least 4 weeks prior to the first administration of study agent
  • If using NSAIDs or other analgesics must be on a stable dose for at least 2 weeks prior to the first administration of study agent
  • If using oral corticosteroids must be on a stable dose equivalent to <= 10 mg of prednisone/day for at least 2 weeks prior to first administration of study agent
  • Are considered eligible according to specified tuberculosis (TB) screening criteria.

Exclusion Criteria:

  • Patients cannot have other inflammatory diseases other than RA that might interfere with the evaluation of the benefit of golimumab therapy
  • No history of treatment with natalizumab, rituximab or cytotoxic agents
  • No history of demyelinating diseases such as multiple sclerosis or optic neuritis or of concurrent congestive heart failure (CHF), lymphoproliferative disease, known malignancy or history of malignancy within the previous 5 years (with the exception of a nonmelanoma skin cancer that has been treated with no evidence of recurrence)
  • No history of, or ongoing, chronic or recurrent infectious disease
  • No serious infection within 2 months prior to first administration of study agent.

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
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Group 1: Placebo
Placebo Subcutaneous (SC) injections every 4 weeks (wks) thru Wk 20 (unless early escape at Wk 16); Golimumab - if early escape, 50 mg SC injections from Wk 16 up to 5 yrs; Golimumab - 50 mg SC injections beginning Wk 24 up to 5 yrs (unless early escape); Golimumab - Dr's discretion after unblinding, dose adjusted from 50 to 100 mg and from 100 to 50mg. Duration of the blinded period will be until the week-24 database lock.
Drug: Placebo
SC injections
Biological: Golimumab 50 mg
SC injections
EXPERIMENTAL: Group 2: Golimumab 50 mg
Golimumab 50 mg SC injections every 4 wks from Wk 0 up to 5 yrs (unless early escape at Wk 16); Golimumab - if early escape, 100 mg SC injections every 4 wks beginning Wk 16 up to 5 yrs; Golimumab - Dr's discretion after unblinding, dose adjusted from 50 to 100 mg and from 100 to 50mg. Duration of the blinded period will be until the week-24 database lock.
Biological: Golimumab 50 mg
SC injections
EXPERIMENTAL: Group 3: Golimumab 100 mg
Golimumab 100 mg SC injections every 4 wks from Wk 0 up to 5 yrs; Golimumab - Dr's discretion after unblinding, dose adjusted from 100 to 50 mg. Duration of the blinded period will be until the week-24 database lock.
Biological: Golimumab 100 mg
SC injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
American College of Rheumatology (ACR) 20 Response at Week 14.
Time Frame: Week 14
ACR 20 response is an improvement of >= 20% from baseline in both the tender and swollen joint count and in at least 3 of the 5 assessments ( patient's assessment of pain visual analog scale (VAS), patient's global assessment of disease activity VAS scale, Physician's global assessment of disease activity VAS scale, Health Assessment Questionnaire and C-reactive protein)
Week 14

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
American College of Rheumatology (ACR) 50 Response at Week 14
Time Frame: Week 14
Number of patients who achieved an ACR 50 response at Week (Wk) 14. ACR 50 response is an improvement of >= 50% from baseline in both the tender and swollen joint count and in at least 3 of the 5 assessments ( patient's assessment of pain visual analog scale (VAS), patient's global assessemnt of disease activity VAS scale, Physician's global assessment of disease activity VAS scale, Health Assessment Questionnaire and C-reactive protein).
Week 14
Disease Activity Index Score 28 (DAS 28) (Using C-reactive Protein) Response at Week 14
Time Frame: Week 14
DAS 28 using C-reactive protein (CRP) is an index to measure disease activity in participants with rheumatoid arthritis which combines tender joint count (28 joints), swollen joint count (28 joints), CRP value, and participant's global assessment of disease activity (using a Visual Analog Scale of 0 to 100 mm). The DAS 28 score ranges from 0 (best) to 10 (worst).
Week 14
American College of Rheumatology (ACR) 20 at Week 24
Time Frame: From Baseline to Week 24
Number of patients who achieved ACR 20 response at Week (Wk) 24. ACR 20 response is an improvement of >= 20% from baseline in both the tender and swollen joint count and in at least 3 of the 5 assessments ( patient's assessment of pain visual analog scale (VAS), patient's global assessemnt of disease activity VAS scale, Physician's global assessment of disease activity VAS scale,HAQ and CRP)
From Baseline to Week 24
Health Assessment Questionnaire (HAQ) Score at Week 24
Time Frame: From Baseline to Week 24
Improvement from baseline in HAQ score at Week 24. This 20-question instrument 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, indicating no difficulty, to 3, indicating inability to perform a task in that area based on the worst score from the questions that pertain to that task. The HAQ score is determined by the average of the 8 scores; HAQ ranges from 0 to 3.
From Baseline to Week 24

Collaborators and Investigators

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

Sponsor

Centocor, Inc.

Collaborators

Schering-Plough

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

February 1, 2006

Primary Completion (ACTUAL)

August 1, 2007

Study Completion (ACTUAL)

May 1, 2012

Study Registration Dates

First Submitted

March 3, 2006

First Submitted That Met QC Criteria

March 3, 2006

First Posted (ESTIMATE)

March 7, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

February 27, 2014

Last Update Submitted That Met QC Criteria

January 27, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR006334
  • C0524T11 (OTHER: Centocor)

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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