A Study of Safety and Effectiveness of Golimumab in Participants With Active Rheumatoid Arthritis Despite Methotrexate Therapy

This study has been completed.
Sponsor:
Collaborator:
Schering-Plough
Information provided by (Responsible Party):
Centocor, Inc.
ClinicalTrials.gov Identifier:
NCT00361335
First received: August 4, 2006
Last updated: March 4, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to assess the clinical effectiveness and safety of golimumab intravenous (IV) infusions every 12 weeks with or without Methotrexate (MTX), compared with MTX alone, in patients with active rheumatoid arthritis (RA) despite concurrent MTX treatment. In addition, the safety of subcutaneous (SC) golimumab injections following transition from IV golimumab infusions will also be evaluated.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Golimumab
Drug: Methotrexate
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, a Fully Human Anti-TNFa Monoclonal Antibody, Administered Intravenously, in Subjects With Active Rheumatoid Arthritis Despite Methotrexate Therapy

Resource links provided by NLM:


Further study details as provided by Centocor, Inc.:

Primary Outcome Measures:
  • Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 14 [ Time Frame: Week 0 to Week 14 ] [ Designated as safety issue: No ]
    An ACR 50 response is defined as a greater than or equal to 50 percentage improvement from baseline in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) 2. greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: a. Patient's assessment of pain (VAS) (0-10 cm) b. Patient's Global Assessment of Disease activity (VAS) (0-10 cm) c. Physician's Global Assessment of Disease Activity (VAS) (0-10 cm) d. Patient's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein (CRP).


Secondary Outcome Measures:
  • Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24 [ Time Frame: Week 0 to Week 24 ] [ Designated as safety issue: No ]
    ACR 50 response is an improvement of greater than or equal to 50 percentage from baseline in both the tender and swollen joint count and in at least 3 of the 5 assessments (patient's assessment of pain, patient's global assessemnt of disease activity, Physician's global assessment of disease activity (based on a scale of 0=no disease to 10=severe disease), HAQ (20 questions on life activities) and CRP blood test to measure inflammation).

  • Number of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14 [ Time Frame: Week 0 to Week 14 ] [ Designated as safety issue: No ]
    ACR 20 response is an improvement of greater than or equal to 20 percentage from baseline in both the tender and swollen joint count and in at least 3 of the 5 assessments (patient's assessment of pain, patient's global assessemnt of disease activity, Physician's global assessment of disease activity [based on a scale of 0=no disease to 10=severe disease), HAQ (20 questions on life activities] and CRP blood test to measure inflammation).

  • Number of Participants With a Disease Activity Index Score 28 (Using C-reactive Protein)Moderate or Good Response at Week 14 [ Time Frame: Week 0 to Week 14 ] [ Designated as safety issue: No ]
    DAS28 using CRP is a measure of tender and swollen joints (28 joints each) and the patient's assessment of disease activity. Values range from 0 (best) to 10 (worst). A score of higher than 5.1 indicates high disease activity, and a score below 3.2 indicates low disease activity. A "Good" response is defined as a patient with a DAS28 score of <= 3.2 at Week 14 with improvement from Baseline in DAS28 score of > 1.2. A "Moderate" response is defined as a patient with DAS28 score of >3.2-5.1 at Week 14 with improvement from baseline in DAS28 score of >1.2 or a DAS28 score of <= 5.1 and improvement from baseline in DAS28 score of >0.6 to 1.2

  • Physical Component Summary (PCS) Score of the Short Form-36 (SF-36) at Week 14 [ Time Frame: Weeks 0 to Week 14 ] [ Designated as safety issue: No ]
    The SF-36 consists of 8 multi-item scales: limitations in physical functioning due to health problems, usual role activities due to physical health problems, bodily pain, usual role activities due to personal or emotional problems, social functioning due to physical or mental health problems, general mental health (psychological distress and well-being), vitality and general health perception. The values are 100=best to 0=worst.


Enrollment: 643
Study Start Date: September 2006
Study Completion Date: September 2009
Arms Assigned Interventions
Experimental: Group I: 2mg/kg Golimumab + MTX
Intravenous (IV) infusions of 2mg/kg golimumab at Week 0 and every 12 weeks thereafter with early escape (an additional 2mg/kg IV infusion of golimumab) and dose regimen adjustment (switch to 4mg/kg IV golimumab), depending on joint assessment results, at Week 16 and 24, respectively. The duration of the combined IV treatment period (initial treatment plus early escape and/or dose regimen adjustment) will be a minimum of 48 weeks. The IV treatment period will be followed by the option of subcutaneous (SC) injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition, patients will receive methotrexate (MTX) at the same dose as that before study entry
Drug: Golimumab
2mg/kg or 4mg/kg will be administered as an IV infusion over 30 minutes
Drug: Methotrexate
Active MTX capsules, filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg MTX tablet, will be administered at the same dose as before the study entry.
Experimental: Group II: 2mg/kg Golimumab only
IV infusions of 2mg/kg golimumab at Week 0 and every 12 weeks thereafter with early escape (addition of MTX) and dose regimen adjustment (addition of MTX or switch to 4mg/kg IV golimumab), depending on joint assessment results, at Week 16 and 24, respectively. The duration of the combined IV treatment period (initial treatment plus early escape and/or dose regimen adjustment) will be a minimum of 48 weeks. The IV treatment period will be followed by the option of SC injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition, patients will receive placebo (sham MTX) capsules
Drug: Golimumab
2mg/kg or 4mg/kg will be administered as an IV infusion over 30 minutes
Drug: Placebo
Placebo solution will be administered through IV infusion in Group V and oral placebo capsules (sham MTX) filled with microcrystalline cellulose (Avicel PH 102) will be administered in Group II and IV.
Other Name: sham MTX
Experimental: Group III: 4mg/kg Golimumab + MTX
IV infusions of 4mg/kg golimumab at Week 0 and every 12 weeks thereafter for a minimum of 48 weeks followed by the option of SC injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition, patients will receive MTX at the same dose as that before study entry.
Drug: Golimumab
2mg/kg or 4mg/kg will be administered as an IV infusion over 30 minutes
Drug: Methotrexate
Active MTX capsules, filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg MTX tablet, will be administered at the same dose as before the study entry.
Experimental: Group IV: 4mg/kg Golimumab only
IV infusions of 4mg/kg golimumab at Week 0 and every 12 weeks thereafter with early escape (addition of MTX) and dose regimen adjustment (addition of MTX), depending on joint assessment results, at Week 16 and 24, respectively. The duration of the combined IV treatment period (initial treatment plus early escape and/or dose regimen adjustment) will be a minimum of 48 weeks. The IV treatment period will be followed by the option of SC injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition, patients will receive placebo (sham MTX) capsules.
Drug: Golimumab
2mg/kg or 4mg/kg will be administered as an IV infusion over 30 minutes
Drug: Placebo
Placebo solution will be administered through IV infusion in Group V and oral placebo capsules (sham MTX) filled with microcrystalline cellulose (Avicel PH 102) will be administered in Group II and IV.
Other Name: sham MTX
Placebo Comparator: Group V: IV Placebo + MTX
IV infusions of placebo at Week 0 and Week 12 with early escape (switch to 4mg/kg IV golimumab) and dose regimen adjustment (switch to 4mg/kg IV golimumab), depending on joint assessment results, at Week 16 and 24, respectively. The duration of the combined IV treatment period (placebo plus golimumab) will be a minimum of 48 weeks. The IV treatment period will be followed by the option of SC injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition patients will receive MTX at the same dose as that before study entry. Participants still receiving placebo injections at Week 48 are not eligible to enter the Extension Study.
Drug: Methotrexate
Active MTX capsules, filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg MTX tablet, will be administered at the same dose as before the study entry.
Drug: Placebo
Placebo solution will be administered through IV infusion in Group V and oral placebo capsules (sham MTX) filled with microcrystalline cellulose (Avicel PH 102) will be administered in Group II and IV.
Other Name: sham MTX

Detailed Description:

This is a Phase III, double blind (neither investigator nor participant knows the treatment received), placebo-controlled (an inactive substance that is compared with the study medication to test whether the study medication has a real effect in clinical study), multicenter, 5-arm (treatment groups) study of golimumab at 2 doses (given with or without MTX over a period of 30 minutes) for at least 48 weeks in patients with active RA despite concurrent MTX therapy. The study consists of a treatment period of golimumab IV infusions (IV Period) which ranges from 48 weeks to approximately 140 weeks, assuming an enrollment period of approximately 92 weeks, and a long-term optional extension period (Extension Study) in which golimumab SC injections will be given for 24 weeks. The end of study will be the time the last participant completes the Week E-40 visit (Extension Study) for safety follow-up assessments. For the IV Period, participants will be randomly assigned to 1 of the 5 treatment groups in a 1:1:1:1:1 ratio (approximately 125 patients per group). At Week 16 and Week 24, joint assessment results will be used to allow participants to enter early escape and dose regimen adjustment, respectively, in a blinded fashion. Treatment will be unblinded after the 48-week database lock and participants will be given the option to participate in the Extension Study and receive SC injections of 50mg golimumab (with or without MTX) every 4 weeks for an additional 24 weeks. Safety will be monitored throughout the study. The entire study duration (IV Period plus Extension Study) for each participant will range from 88 weeks up to 192 weeks, assuming an enrollment period of approximately 92 weeks.

  Eligibility

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

Inclusion Criteria:

- Must have a diagnosis of active rheumatoid arthritis (RA) (according to the revised 1987 criteria of the ARA (American Rheumatism Association) with at least 4 swollen and 4 tender joints for at least 3 months prior to screening - Have been treated with and tolerated methotrexate (MTX) at a dose of at least 15 mg per week for at least 3 months prior to screening - Have been on a stable MTX dose of greater than or equal to 15 mg per week and less than or eual to 25 mg per week for at least 4 weeks prior to screening - If using non steroidal anti-inflammatory agents (such as naproxen) or other pain relievers for RA, must be on a stable dose for at least 2 weeks prior to the first administration of study agent

Exclusion Criteria:

- Participants having known hypersensitivity (severe allergy) to human immunoglobulin proteins or other components of golimumab - Having known clinically serious adverse reaction to a biologic anti-TNF agent - Have had history of latent or active granulomatous infection, including tuberculosis, histoplasmosis, or coccidioidomycosis, prior to screening

  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: NCT00361335

  Show 72 Study Locations
Sponsors and Collaborators
Centocor, Inc.
Schering-Plough
Investigators
Study Director: Centocor, Inc. Clinical Trial Centocor, Inc.
  More Information

No publications provided by Centocor, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Centocor, Inc.
ClinicalTrials.gov Identifier: NCT00361335     History of Changes
Other Study ID Numbers: CR012781, C0524T12, 2005-003232-21
Study First Received: August 4, 2006
Results First Received: February 24, 2010
Last Updated: March 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Centocor, Inc.:
Rheumatoid arthritis
Golimumab
Methotrexate
Tumor Necrosis Factor-alpha
Immunology

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antibodies, Monoclonal
Methotrexate
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014