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: February 7, 2014
Last verified: February 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 or placebo
Drug: golimumab
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:
  • To evaluate the efficacy of golimumab + MTX in reducing signs and symptoms of RA (as assessed by American College of Rheumatology [ACR] 20 in patients with inadequate disease control despite treatment with etanercept + MTX or adalimumab + MTX [ Time Frame: The primary outcome will be measured at Week 14. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The efficacy of golimumab 2 mg/kg IV therapy + MTX defined by the relative proportions of randomized patients in the golimumab IV group (with a loading dose) and the golimumab SC groups who achieve an ACR 20 response [ Time Frame: At Week 52 compared to your response at Week 16 ] [ Designated as safety issue: No ]
  • Evaluation of safety, additional measures of response, health related outcomes, patient preference,blood tests measuring inflammation, ribonucleic acid (RNA) analysis, trough serum golimumab concentrations, and the development of antibodies to golimumab. [ Time Frame: Starting at Week 0 through Week 64 ] [ Designated as safety issue: Yes ]
  • Pharmacogenomics (the study of how people's genetic make-up affects their response to medicines) will also be studied in consenting patients. [ Time Frame: Starting at Week 0 through Week 64 ] [ Designated as safety issue: No ]
  • The onset of response to golimumab 50 mg SC every 4 weeks + MTX as defined by the proportion of patients who achieve an ACR 20 response [ Time Frame: Within 2 weeks of initiating therapy ] [ Designated as safety issue: No ]
  • The persistence of response to golimumab 50 mg SC every 4 weeks + MTX as defined by the proportion of patients who achieve a DAS28 "good" response [ Time Frame: Week 16 through Week 52 ] [ Designated as safety issue: No ]

Enrollment: 436
Study Start Date: December 2009
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 001
golimumab Golimumab 50 mg SC injections every 4 weeks through Week 12 (Weeks 0 4 8 and 12) + MTX then Golimumab 50 mg SC every 4 weeks (Weeks 16 20 24 28 32 36 40 44 and 48) + MTX
Drug: golimumab or placebo
then Golimumab 50 mg SC every 4 weeks (Weeks 16, 20, 24, 28, 32, 36, 40, 44, and 48) + MTX
Drug: golimumab
Golimumab 50 mg SC injections every 4 weeks through Week 12 (Weeks 0, 4, 8, and 12) + MTX
Experimental: 002
golimumab or placebo Golimumab 50 mg SC injections every 4 weeks through Week 12 then golimumab 50 mg SC every 4 weeks + MTX. Active golimumab SC injections at Weeks 16 20 24 28 32 36 40 44 and 48. Patients will also receive placebo IV infusions at Weeks 16 20 28 36 and 44
Drug: golimumab or placebo
Golimumab 50 mg SC injections every 4 weeks through Week 12, then golimumab 50 mg SC every 4 weeks + MTX. Active golimumab SC injections at Weeks 16, 20, 24, 28, 32, 36, 40, 44, and 48. Patients will also receive placebo IV infusions at Weeks 16, 20, 28, 36, and 44
Experimental: 003
golimumab or placebo Golimumab 50 mg SC injections every 4 weeks through Week 12 then golimumab 2 mg/kg IV every 8 weeks + MTX. Active golimumab IV infusions at Weeks 16 20 28 36 and 44. Patients will also receive placebo SC injections at Weeks 16 20 24 28 32 36 40 44 and 48.
Drug: golimumab
Golimumab 50 mg SC injections every 4 weeks through Week 12 (Weeks 0, 4, 8, and 12) + MTX
Drug: golimumab or placebo
Golimumab 50 mg SC injections every 4 weeks through Week 12, then golimumab 50 mg SC every 4 weeks + MTX. Active golimumab SC injections at Weeks 16, 20, 24, 28, 32, 36, 40, 44, and 48. Patients will also receive placebo IV infusions at Weeks 16, 20, 28, 36, and 44

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) inhibitor. Golimumab is a type of TNF inhibitor. TNF is a naturally occurring substance in the body and this substance may cause long-term inflammation. Golimumab may help fight your disease by blocking the activity of TNF in your body. This study will assess the safety of golimumab and determine if there is a reduction of the pain and swelling in the joints of patients with rheumatoid arthritis treated with golimumab. The effect of golimumab on physical function, and the quality of life in patients with rheumatoid arthritis will also be assessed. Golimumab will be given by a subcutaneous injection (SC) every 4 weeks at doses of 50 mg and possibly by intravenous injection (IV) every 8 weeks at 2 mg/kg. Golimumab is given by a SC injection with a needle inserted under your skin in the back of your upper arm, your upper thigh, stomach area or by IV in your arm. If you are eligible to take part in this study, you will initiate treatment with open-label golimumab SC injections every 4 weeks. During the first 12 weeks you and your doctor will know what medication you are receiving, this is called open-label. Starting at Week 16, depending on how your RA has improved, you will be put into one of three groups where each group gets a different treatment. If your study doctor sees an improvement of in your disease you can continue to receive an injection of golimumab 50 mg SC 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 four weeks along with placebo drug IV every eight weeks and a two in three chance of being put in the group receiving 2mg/kg IV every eight weeks along with placebo SC every four weeks. Starting with Week 16 if you are placed in Group 1, the study will remain open labeled. If you are randomized to Groups 2a or 2b, the study is "blinded." This means that neither you nor your study doctor will know in which group you are placed. However, if needed for safety or health reasons, your study doctor can find out your treatment at any time. Placebo is an inactive treatment that looks the same as the study drug golimumab, but does not contain any active medication. Your disease will be measured by your physician using standards called American College of Rheumatology (ACR) 20 and Disease Activity Score (DAS) 28. For example, if a study reported that 55% of patients achieved ACR20, that means 55% of patients in the study achieved a 20% improvement in tender or swollen joint counts as well as 20% improvement in three of the other five criteria. DAS28 is based on counts of the number of painful joints and the number of swollen joints you have out of 28 joints. All patients will receive golimumab 50 mg subcutaneous injection every 4 weeks + methotrexate for 16 weeks. Patients whose disease shows pronounced improvement will continue to receive this therapy every 4 weeks for 36 more weeks. Patients who do not achieve a DAS-28 "good" response, as defined by EULAR criteria, will receive either golimumab 50 mg subcutaneous injection every 4 weeks + methotrexate for 36 more weeks OR golimumab 2 mg/kg IV every 8 weeks + methotrexate for 34 more weeks.

  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
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
Last Updated: February 7, 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
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Immune System Diseases
TNFR-Fc fusion protein
Immunoglobulin G
Adalimumab
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on April 17, 2014