Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Golimumab in Rheumatoid Arthritis Participants With an Inadequate Response to Etanercept (ENBREL) or Adalimumab (HUMIRA)

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Janssen Biotech, Inc.
ClinicalTrials.gov Identifier:
NCT01004432
First received: October 29, 2009
Last updated: October 20, 2014
Last verified: October 2014
  Purpose

The purpose of this study is to evaluate the efficacy and safety of switching rheumatoid arthritis (RA) participants who have an inadequate response to their current treatment with either etanercept + methotrexate or adalimumab + methotrexate to treatment with golimumab 50 milligram (mg) subcutaneous (SC) injection (a needle inserted under the skin in the back of upper arm, upper thigh or stomach area) every 4 weeks + methotrexate. This study is also designed to evaluate the benefit and safety of switching participants from treatment with golimumab 50 mg subcutaneous injection every 4 weeks + methotrexate to golimumab 2 milligram per kilogram (mg/kg) intravenous every 8 weeks + methotrexate, for those who do not achieve a marked improvement of their RA at Week 16.


Condition Intervention Phase
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Drug: Golimumab 50 mg SC
Drug: Golimumab 2 mg/kg IV
Drug: Methotrexate (MTX)
Drug: Placebo SC
Drug: Placebo IV
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Golimumab Phase 3b, Multicenter, Switch Assessment of Subcutaneous and Intravenous Efficacy in Rheumatoid Arthritis Patients Who Have Inadequate Disease Control Despite Treatment With Etanercept (ENBREL) or Adalimumab (HUMIRA)

Resource links provided by NLM:


Further study details as provided by Janssen Biotech, Inc.:

Primary Outcome Measures:
  • Percentage of Participants Achieving Erythrocyte Sedimentation Rate (ESR)-Based American College of Rheumatology [ACR] 20 Response at Week 14 [ Time Frame: Week 14 ] [ Designated as safety issue: No ]
    Erythrocyte Sedimentation Rate (ESR)-based ACR 20 response: greater than or equal to (>=) 20 percent (%) improvement from Baseline in tender (68 joints assessed) and swollen (66 joints assessed) joint counts and >=20% improvement from Baseline in 3 of the following 5 assessments: 1- Participant's assessment of pain using Visual Analog Scale (VAS) (0 to 10 centimeters [cm]), 2- Participant's global assessment of disease activity using VAS (0 to 10 cm), 3- Physician's global assessment of disease activity using VAS (0 to 10 cm), 4- Participant's assessment of physical function as measured by the Disability Index of the Health Assessment Questionnaire (HAQ-DI) (score of 0-3 in 8 functional areas), 5- ESR.


Secondary Outcome Measures:
  • Percentage of Participants Who Achieved Erythrocyte Sedimentation Rate (ESR)-Based ACR20 Response at Week 2 [ Time Frame: Within 2 weeks of initiating therapy ] [ Designated as safety issue: No ]
    Erythrocyte Sedimentation Rate (ESR)-based ACR 20 response: greater than or equal to (>=) 20 percent (%) improvement from Baseline in tender (68 joints assessed) and swollen (66 joints assessed) joint counts and >=20% improvement from Baseline in 3 of the following 5 assessments: 1- Participant's assessment of pain using Visual Analog Scale (VAS) (0 to 10 centimeters [cm]), 2- Participant's global assessment of disease activity using VAS (0 to 10 cm), 3- Physician's global assessment of disease activity using VAS (0 to 10 cm), 4- Participant's assessment of physical function as measured by the Disability Index of the Health Assessment Questionnaire (HAQ-DI) (score of 0-3 in 8 functional areas), 5- ESR.

  • Percentage of Participants Who Achieved Erythrocyte Sedimentation Rate (ESR)-Based Disease Activity Score (DAS28) Response at Week 16 and Maintained Response Through Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    Erythrocyte Sedimentation Rate (ESR)-based disease activity score for 28-joints count (DAS28) as defined by European League Against Rheumatism (EULAR), response criteria was used to assess individual response as none, moderate, or good, depending on the extent of change from Baseline and the level of disease activity reached. A participant was classified as having achieved a DAS28 good response if, DAS28 was less than or equal to (<=) 3.2 at a given visit and improvement from Baseline was >1.2. Percentage of participants, who achieved ESR-based DAS 28 good response at Week 16 and maintained that response through Week 52, is reported.

  • Percentage of Participants Who Achieved Erythrocyte Sedimentation Rate (ESR)-Based ACR20 Response at Week 52 Relative to Week 16 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    Erythrocyte Sedimentation Rate (ESR)-based ACR 20 response: >=20 % improvement from Week 16 in tender (68 joints assessed) and swollen (66 joints assessed) joint counts and >=20% improvement from Week 16 in 3 of the following 5 assessments: 1- Participant's assessment of pain using VAS (0 to 10 cm), 2- Participant's global assessment of disease activity using VAS (0 to 10 cm), 3- Physician's global assessment of disease activity using VAS (0 to 10 cm), 4- Participant's assessment of physical function as measured by the Disability Index of the Health Assessment Questionnaire (HAQ-DI) (score of 0-3 in 8 functional areas), 5- ESR. Percentage of participants, who achieved ESR-based ACR 20 responses at Week 52 relative to Week 16, is reported.

  • Percentage of Participants Who Achieved ESR-based and C-Reactive Protein (CRP)-Based ACR20 Response at Week 76 Relative to Week 16 [ Time Frame: Week 76 ] [ Designated as safety issue: No ]
    Erythrocyte Sedimentation Rate (ESR)-based/ C Reactive Protein (CRP)-based ACR 20 response: >=20 % improvement from Week 16 in tender (68 joints assessed) and swollen (66 joints assessed) joint counts and >=20% improvement from Week 16 in 3 of the following 5 assessments: 1- Participant's assessment of pain using VAS (0 to 10 cm), 2- Participant's global assessment of disease activity using VAS (0 to 10 cm), 3- Physician's global assessment of disease activity using VAS (0 to 10 cm), 4- Participant's assessment of physical function as measured by the Disability Index of the Health Assessment Questionnaire (HAQ-DI) (score of 0-3 in 8 functional areas), 5- ESR or CRP. Percentage of participants, who achieved ESR/ CRP-based ACR 20 responses at Week 76 relative to Week 16, is reported.

  • Change in ESR-based DAS28 Score at Week 76 Relative to Week 52 [ Time Frame: Week 52, 76 ] [ Designated as safety issue: No ]
    Erythrocyte Sedimentation Rate (ESR)-based disease activity score for 28-joints count (DAS28) was calculated from number of swollen joint counts (SJC) and tender joint counts (TJC) using 28 joints count, ESR, and patient global assessment of disease activity (participant rated arthritis activity assessment with scores ranging 0 to 10; higher scores indicated greater disease activity). Total ESR-based DAS28 score range: 0 to 9.4, higher score=more disease activity.


Enrollment: 433
Study Start Date: December 2009
Study Completion Date: October 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open-label (OL) Overall Group: Golimumab 50 mg SC + MTX
All enrolled and dosed participants receive golimumab 50 milligram (mg) subcutaneous (SC) injection every 4 weeks + Methotrexate (MTX) from Week 0 to Week 12.
Drug: Golimumab 50 mg SC
Golimumab 50 milligram (mg) subcutaneous (SC) injection every 4 weeks.
Drug: Methotrexate (MTX)
Participants will continue taking their current Methotrexate (MTX) treatment regimen.
Experimental: Double blind (DB) Group 2a: Golimumab 50mg SC & Placebo IV+MTX
Participants, who do not achieve Disease Activity Score in 28 joints (DAS28) good response at Week 16, will be randomly assigned to receive golimumab 50 mg SC injection every 4 weeks + MTX from Week 16 to Week 48, along with placebo matched to golimumab intravenous infusion (IV) at Week 16, 20, 28, 36, and 44.
Drug: Golimumab 50 mg SC
Golimumab 50 milligram (mg) subcutaneous (SC) injection every 4 weeks.
Drug: Methotrexate (MTX)
Participants will continue taking their current Methotrexate (MTX) treatment regimen.
Drug: Placebo IV
Placebo matched to golimumab intravenous infusion every 8 weeks.
Experimental: DB Group 2b: Golimumab 2mg/kg IV & Placebo SC + MTX
Participants, who do not achieve DAS28 good response at Week 16, will be randomly assigned to receive golimumab 2 milligram per kilogram (mg/kg) intravenous infusion (IV) + MTX, at Week 16, 20, 28, 36 and 44, along with placebo matched to golimumab SC injection every 4 weeks from Week 16 to Week 48.
Drug: Golimumab 2 mg/kg IV
Golimumab 2 milligram per kilogram (mg/kg) intravenous infusion every 8 weeks.
Drug: Methotrexate (MTX)
Participants will continue taking their current Methotrexate (MTX) treatment regimen.
Drug: Placebo SC
Placebo matched to golimumab SC injection every 4 weeks.
Experimental: OL Group 1: Golimumab 50 mg SC + MTX
Participants, who achieve DAS28 good response at Week 16, will receive golimumab 50 mg SC injection every 4 weeks + MTX from Week 16 to Week 48.
Drug: Golimumab 50 mg SC
Golimumab 50 milligram (mg) subcutaneous (SC) injection every 4 weeks.
Drug: Methotrexate (MTX)
Participants will continue taking their current Methotrexate (MTX) treatment regimen.
Experimental: OL Study Extension Group: Golimumab 50 mg SC + MTX
Participants who complete the main study (Week 0 to Week 52), do not meet lack of efficacy criteria, and participate in the OL study extension, will receive golimumab 50 mg SC injection every 4 weeks + MTX from Week 52 to Week 72.
Drug: Golimumab 50 mg SC
Golimumab 50 milligram (mg) subcutaneous (SC) injection every 4 weeks.
Drug: Methotrexate (MTX)
Participants will continue taking their current Methotrexate (MTX) treatment regimen.

Detailed Description:

The study consists of a main study and a voluntary, open-label (participants and researchers are aware about the treatment participants are receiving), 24-week study extension. The main study includes a Screening Run-in Period (Week -6 to Week 0), an Open-label Treatment Period (Week 0 to Week 16), an Open-label or Double-blind Treatment Period (Week 16 to Week 52). The main study also includes a Follow-up Period from Week 52 through Week 64 for those participants who will not participate in the 24-week study extension. Participants, participating in 24-week extension (at Week 52), will receive open-label golimumab SC injections every 4 weeks from Week 52 up to Week 72 and will be followed-up up to Week 88. All eligible participants will initiate the treatment with open-label golimumab SC injection every 4 weeks up to Week 12. At Week 16, depending upon the treatment response either participants will continue to receive open-label golimumab SC injection every 4 weeks up to Week 48 or participants will be randomly assigned to receive following 2 treatments: 1- golimumab 50mg SC injection every 4 weeks along with placebo intravenous infusion every 8 weeks through Week 48; 2- Placebo SC injection every 4 weeks along with golimumab 2mg/kg intravenous infusion every 8 weeks through Week 48. At Week 52, participants who choose to participate in the 24-week study extension will receive open-label golimumab 50 mg SC injections every 4 weeks through Week 72. Participants' safety will be monitored throughout the study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have inadequate RA disease control prior to the first administration of study agent despite treatment with etanercept (Enbrel) + methotrexate or adalimumab (Humira) + methotrexate (MTX)
  • Must have received a stable dose of MTX greater than or equal to (>=) 7.5 milligram (mg) per week to less than or equal to (<=) 25 mg per week for at least 4 consecutive weeks prior to the first screening visit and must plan to maintain that dose throughout the study
  • Participants must have received etanercept or adalimumab in combination with MTX for a minimum of 3 months prior to the first visit
  • Negative tuberculosis (TB) test
  • Are capable of providing informed consent, which must be obtained prior to any study-related procedures

Exclusion Criteria:

  • Have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, or are frequently in contact with individuals who carry active TB infection
  • Have inflammatory diseases other than RA, including but not limited to psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, primary Sjogren's or Lyme disease
  • Have demonstrated a discernible improvement in disease activity between screening and prior to the first golimumab injection at Week 0
  • Have any known malignancy or have a 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)
  • Have a history of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease such as lymphadenopathy of unusual size or location
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01004432

  Hide Study Locations
Locations
United States, Alabama
Birmingham, Alabama, United States
Huntsville, Alabama, United States
Tuscaloosa, Alabama, United States
United States, Arizona
Mesa, Arizona, United States
Phoenix, Arizona, United States
United States, Arkansas
Hot Springs, Arkansas, United States
Little Rock, Arkansas, United States
United States, California
Covina, California, United States
Hemet, California, United States
Loma Linda, California, United States
Long Beach, California, United States
Murrieta, California, United States
Santa Maria, California, United States
Santa Monica, California, United States
Torrance, California, United States
Van Nuys, California, United States
Victorville, California, United States
Whittier, California, United States
United States, Connecticut
Bridgeport, Connecticut, United States
Hamden, Connecticut, United States
Trumbull, Connecticut, United States
United States, Florida
Aventura, Florida, United States
Fort Lauderdale, Florida, United States
Jacksonville, Florida, United States
Naples, Florida, United States
Orange Park, Florida, United States
Orlando, Florida, United States
Palm Harbor, Florida, United States
Plantation, Florida, United States
Sarasota, Florida, United States
Tampa, Florida, United States
United States, Georgia
Duluth, Georgia, United States
United States, Idaho
Coeur D'Alene, Idaho, United States
Idaho Falls, Idaho, United States
United States, Illinois
Rockford, Illinois, United States
United States, Indiana
South Bend, Indiana, United States
United States, Iowa
Bettendorf, Iowa, United States
United States, Kansas
Kansas City, Kansas, United States
United States, Kentucky
Bowling Green, Kentucky, United States
United States, Louisiana
Monroe, Louisiana, United States
New Orleans, Louisiana, United States
United States, Maryland
Wheaton, Maryland, United States
United States, Minnesota
Rochester, Minnesota, United States
United States, Mississippi
Flowood, Mississippi, United States
Tupelo, Mississippi, United States
United States, Missouri
Clayton, Missouri, United States
Florissant, Missouri, United States
United States, Nebraska
Lincoln, Nebraska, United States
United States, New Jersey
Freehold, New Jersey, United States
United States, New York
Brooklyn, New York, United States
Mineola, New York, United States
Plainview, New York, United States
Rochester, New York, United States
Smithtown, New York, United States
United States, North Carolina
Charlotte, North Carolina, United States
Greenville, North Carolina, United States
Hickory, North Carolina, United States
Wilmington, North Carolina, United States
United States, Ohio
Akron, Ohio, United States
Columbus, Ohio, United States
Mayfield, Ohio, United States
Middleburg Heights, Ohio, United States
United States, Oklahoma
Edmond, Oklahoma, United States
Oklahoma City, Oklahoma, United States
United States, Oregon
Lake Oswego, Oregon, United States
United States, Pennsylvania
Bethlehem, Pennsylvania, United States
Duncansville, Pennsylvania, United States
West Reading, Pennsylvania, United States
Wexford, Pennsylvania, United States
United States, South Carolina
Charleston, South Carolina, United States
Columbia, South Carolina, United States
Myrtle Beach, South Carolina, United States
United States, Tennessee
Hixson, Tennessee, United States
Jackson, Tennessee, United States
Kingsport, Tennessee, United States
Knoxville, Tennessee, United States
Nashville, Tennessee, United States
United States, Texas
Austin, Texas, United States
Carrollton, Texas, United States
Dallas, Texas, United States
Houston, Texas, United States
San Antonio, Texas, United States
United States, Virginia
Arlington, Virginia, United States
Chesapeake, Virginia, United States
United States, Washington
Seattle, Washington, United States
Spokane, Washington, United States
United States, West Virginia
Beckley, West Virginia, United States
Clarksburg, West Virginia, United States
United States, Wisconsin
Glendale, Wisconsin, United States
Austria
Vienna, Austria
Belgium
Brussel, Belgium
Genk, Belgium
Gent, Belgium
Liège, Belgium
Merksem, Belgium
Canada, Alberta
Edmonton, Alberta, Canada
Canada, British Columbia
Kelowna, British Columbia, Canada
Vancouver, British Columbia, Canada
Canada, Manitoba
Winnipeg, Manitoba, Canada
Canada, Ontario
Hamilton, Ontario, Canada
Canada, Quebec
Montreal, Quebec, Canada
Canada
Quebec, Canada
St Johns, Canada
Germany
Hamburg, Germany
Herne, Germany
München, Germany
Ratingen, Germany
Greece
Heraklion- Crete, Greece
Thessalonikis, Greece
Sweden
Stockholm, Sweden
United Kingdom
Cannock, United Kingdom
Leeds, United Kingdom
London, United Kingdom
Manchester, United Kingdom
Merseyside, United Kingdom
Newcastle Upon Tyne, United Kingdom
Wigan, United Kingdom
Sponsors and Collaborators
Janssen Biotech, Inc.
Merck Sharp & Dohme Corp.
Investigators
Study Director: Janssen Biotech, Inc. Clinical Trial Janssen Biotech, Inc.
  More Information

No publications provided

Responsible Party: Janssen Biotech, Inc.
ClinicalTrials.gov Identifier: NCT01004432     History of Changes
Other Study ID Numbers: CR016663, CNTO148ART3002, 2009-010582-23, GO SAVE
Study First Received: October 29, 2009
Results First Received: March 13, 2014
Last Updated: October 20, 2014
Health Authority: United States: Food and Drug Administration
Austria: Agency for Health and Food Safety
Belgium: Ministry of Social Affairs, Public Health and the Environment
Canada: Canadian Institutes of Health Research
Germany: Federal Institute for Drugs and Medical Devices
Great Britain: Department of Health
Greece: Ministry of Health and Welfare
Sweden: Medical Products Agency
United States: Federal Government
Austria: Federal Ministry for Health and Women
Great Britain: Research Ethics Committee

Keywords provided by Janssen Biotech, Inc.:
humira, remicade
rheumatoid arthritis
enbrel failure
humira failure
arthritis
enbrel

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Adalimumab
Methotrexate
TNFR-Fc fusion protein
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Central Nervous System Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on November 20, 2014