Golimumab in Rheumatoid Arthritis Patients 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: August 26, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to evaluate the efficacy and safety of switching rheumatoid arthritis (RA) patients who have an inadequate response to their current treatment with either etanercept + methotrexate or adalimumab + methotrexate to treatment with golimumab 50 mg subcutaneous injection (a needle inserted under your skin in the back of your upper arm, upper thigh or stomach area) every 4 weeks + methotrexate. This study is also designed to evaluate the benefit and safety of switching patients from treatment with golimumab 50 mg subcutaneous injection every 4 weeks + methotrexate to golimumab 2 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 & Placebo IV + MTX: Golimumab 50 mg SC + Methotrexate (MTX) + Placebo IV
Drug: Golimumab 2mg/kg IV & Placebo SC + MTX
Drug: Golimumab 50 mg SC + Methotrexate (MTX)
Drug: Open label Golimumab 50 mg SC + Methotrexate (MTX)
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 Sequential 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 Subjects Achieving (Erythrocyte Sedimentation Rate) ESR-based American College of Rheumatology [ACR] 20 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 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 Subjects 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 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 Subjects 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 Subjects 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 Baseline in tender (68 joints assessed) and swollen (66 joints assessed) joint counts and >=20% improvement 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.


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: OL Group 1: Golimumab Open Label 50 mg SC + MTX
OL Group 1: Golimumab Open Label 50 mg SC+ MTX: Open label Golimumab 50 mg SC + Methotrexate (MTX): Subjects who achieved DAS28 good response at Week 16. Golimumab 50 mg SC injection every 4 weeks + MTX from Week 16 - 48. Where OL is used to abbreviate Open-Label.
Drug: Golimumab 50 mg SC + Methotrexate (MTX)
OL Group 1: Golimumab Open Label 50 mg SC + MTX: Open label Golimumab 50 mg SC + Methotrexate (MTX): Subjects who achieved DAS28 good response at Week 16. Golimumab 50 mg SC injection every 4 weeks + MTX from Week 16 - 48.
Experimental: DB Group 2a: Golimumab 50 mg SC & Placebo IV + MTX
DB Group 2a: Golimumab 50 mg SC & Placebo IV + MTX: Golimumab 50 mg SC + Methotrexate (MTX) + Placebo IV: Subjects who did not achieved good DAS28 response at Week 16. Randomized to receive Golimumab 50 mg SC injection every 4 weeks + MTX from Week 16 - 48. Placebo IV at Weeks 16, 20, 28, 36, and 44. Where DB is used to abbreviate Double Blind.
Drug: Golimumab 50 mg SC & Placebo IV + MTX: Golimumab 50 mg SC + Methotrexate (MTX) + Placebo IV
DB Group 2a: Golimumab 50 mg SC & Placebo IV + MTX: Golimumab 50 mg SC + Methotrexate (MTX) + Placebo IV: Subjects who did not achieved good DAS28 response at Week 16. Randomized to receive Golimumab 50 mg SC injection every 4 weeks + MTX from Week 16 - 48. Placebo IV at Weeks 16, 20, 28, 36, and 44. Where DB is used to abbreviate Double Blind.
Experimental: DB Group 2b: Golimumab 2 mg/kg IV & Placebo SC + MTX
DB Group 2b: Golimumab 2mg/kg IV & Placebo SC + MTX: Golimumab 2mg/kg + Methotrexate (MTX) + Placebo SC: Subjects who did not achieve DAS28 good response at Week 16. Randomized to receive Golimumab 2mg/kg IV at Weeks 16, 20, 28, 36 and 44 + MTX. Placebo SC every 4 weeks from Week 16 - 48. Where DB is used to abbreviate Double Blind.
Drug: Golimumab 2mg/kg IV & Placebo SC + MTX
DB Group 2b: Golimumab 2mg/kg IV & Placebo SC + MTX: Golimumab 2mg/kg + Methotrexate (MTX) + Placebo SC: Subjects who did not achieve DAS28 good response at Week 16. Randomized to receive Golimumab 2mg/kg IV at Weeks 16, 20, 28, 36 and 44 + MTX. Placebo SC every 4 weeks from Week 16 - 48. Where DB is used to abbreviate Double Blind.
Experimental: OL Overall Group: Golimumab 50 mg SC + MTX
OL Overall Group: Golimumab 50 mg SC + Methotrexate (MTX): All enrolled and dosed subjects. Golimumab 50 mg SC injection every 4 weeks + MTX from Week 0 - 12. Where OL is used to abbreviate Open-Label.
Drug: Open label Golimumab 50 mg SC + Methotrexate (MTX)
OL Overall Group: Golimumab 50 mg SC + Methotrexate (MTX): All enrolled and dosed subjects. Golimumab 50 mg SC injection every 4 weeks + MTX from Week 0 - 12. Where OL is used to abbreviate Open-Label.

Detailed Description:

The main purpose of this study is to assess the effects (good and bad) of golimumab for rheumatoid arthritis (RA) in patients previously treated with another tumor necrosis factor (TNF), a naturally occurring substance in the body that may cause long-term inflammation, inhibitor. If you are eligible to take part in this study, you will initiate treatment with open-label golimumab SC injections every 4 weeks. Starting at Week 16, if your study doctor sees an improvement in your disease you can continue to receive SC injections of golimumab 50 mg every 4 weeks through Week 48. If your disease has not improved you will be randomly placed into one of two study groups. You will have approximately a one in three chance of being put in the group receiving golimumab 50mg SC every 4 weeks along with placebo drug IV every 8 weeks and a two in three chance of being put in the group receiving 2mg/kg IV every 8 weeks along with placebo SC every 4 weeks, through week 48.

  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 enbrel + methotrexate or humira + methotrexate
  • Must have received a stable dose of MTX >=7.5 mg/week to <=25 mg/week for at least 4 consecutive weeks prior to the first screening visit and must plan to maintain that dose throughout the study
  • Patients must have received etanercept or adalimumab in combination with MTX for a minimum of 3 months prior to the first visit
  • Negative tuberculosis 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

  Show 117 Study Locations
Sponsors and Collaborators
Janssen Biotech, Inc.
Merck Sharp & Dohme Corp.
Investigators
Study Director: Centocor, Inc. Clinical Trial Centocor, 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: August 26, 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

Keywords provided by Janssen Biotech, Inc.:
humira, remicade
rheumatoid arthritis
enbrel failure
humira failure
subcutaneous injection
arthritis
IV
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 October 23, 2014