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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

October 29, 2009
October 20, 2014
December 2009
July 2013   (final data collection date for primary outcome measure)
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.
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 ]
Complete list of historical versions of study NCT01004432 on ClinicalTrials.gov Archive Site
  • 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.
  • 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 ]
  • 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 measuing 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 ]
Not Provided
Not Provided
 
Golimumab in Rheumatoid Arthritis Participants With an Inadequate Response to Etanercept (ENBREL) or Adalimumab (HUMIRA)
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)

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Arthritis
  • Arthritis, Rheumatoid
  • Autoimmune Diseases
  • Drug: Golimumab 50 mg SC
    Golimumab 50 milligram (mg) subcutaneous (SC) injection every 4 weeks.
  • 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.
  • Drug: Placebo IV
    Placebo matched to golimumab intravenous infusion every 8 weeks.
  • 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.
    Interventions:
    • Drug: Golimumab 50 mg SC
    • Drug: Methotrexate (MTX)
  • 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.
    Interventions:
    • Drug: Golimumab 50 mg SC
    • Drug: Methotrexate (MTX)
    • Drug: Placebo IV
  • 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.
    Interventions:
    • Drug: Golimumab 2 mg/kg IV
    • Drug: Methotrexate (MTX)
    • Drug: Placebo SC
  • 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.
    Interventions:
    • Drug: Golimumab 50 mg SC
    • Drug: Methotrexate (MTX)
  • 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.
    Interventions:
    • Drug: Golimumab 50 mg SC
    • Drug: Methotrexate (MTX)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
433
October 2013
July 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Austria,   Belgium,   Canada,   Germany,   Greece,   Sweden,   United Kingdom
 
NCT01004432
CR016663, CNTO148ART3002, 2009-010582-23, GO SAVE
Yes
Janssen Biotech, Inc.
Janssen Biotech, Inc.
Merck Sharp & Dohme Corp.
Study Director: Janssen Biotech, Inc. Clinical Trial Janssen Biotech, Inc.
Janssen Biotech, Inc.
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP