Study Conducted in Subjects With Rheumatoid Arthritis Who Have Moderate to Severe Disease Activity Despite Methotrexate Therapy With or Without Other Non Biologic Disease Modifying Antirheumatic Drugs (DMARDs)for at Least 12 Weeks Prior to Screening

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01578850
First received: April 12, 2012
Last updated: May 25, 2016
Last verified: May 2016
  Purpose
To compare the maintenance of efficacy of the combination of etanercept 50 mg once weekly plus methotrexate with or without other disease modifying antirheumatic drugs therapy with that of methotrexate with or without other disease modifying antirheumatic drugs therapy at Week 52 in subjects with moderately to severely active rheumatoid arthritis who have achieved low disease activity after 24 weeks of therapy with open label etanercept 50 mg once weekly plus MTX with or without other disease modifying antirheumatic drugs therapy.

Condition Intervention Phase
Rheumatoid Arthritis
Drug: Etanercept
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind Placebo-controlled Study Of The Maintenance Of Efficacy Of Etanercept Plus Dmard(s) Compared With Dmard(s) Alone In Subjects With Rheumatoid Arthritis After Achieving An Adequate Response With Etanercept Plus Dmard(s)

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Percentage of Participants Who Remained in Low Disease Activity (LDA) (Disease Activity Score in 28 Joints-erythrocyte Sedimentation Rate [DAS28-ESR] <3.2) at Week 52. [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Proportion of participants who remained in LDA DAS28-ESR <3.2 at Week 52 is presented below.


Secondary Outcome Measures:
  • Percentage of Participants Who Remained in Remission at Week 52 (DAS28-ESR) [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Proportion of participants who remained in Remission (DAS28-ESR <2.6) at Week 52.

  • Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-C-reactive Protein [CRP]) at Each Visit During Period 1 [ Time Frame: Baseline, Weeks 4, 8, 16 and 24 ] [ Designated as safety issue: No ]
    Proportion of participants who achieved LDA (DAS28-ESR and DAS28-CRP at each visit during period 1 is presented below.

  • Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2 [ Time Frame: Baseline, Weeks 24, 28, 36, 44 and 52 ] [ Designated as safety issue: No ]
    Proportion of participants who achieved LDA (DAS28-ESR and DAS28-CRP at each visit during period 2 is presented below.

  • Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 1 [ Time Frame: Baseline, Weeks 4, 8, 16 and 24 ] [ Designated as safety issue: No ]
    Proportion of participants who achieved remission (DAS28-ESR and DAS28-CRP at each visit during period 1 is presented below.

  • Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2 [ Time Frame: Baseline, Weeks 24, 28, 36, 44 and 52 ] [ Designated as safety issue: No ]
    Proportion of participants who achieved LDA (DAS28-ESR and DAS28-CRP at each visit during period 2 is presented below.

  • Change From Baseline in DAS28-CRP and DAS28-ESR in Period 1 [ Time Frame: Baseline, Weeks 4, 8, 16 and 24 ] [ Designated as safety issue: No ]
    The DAS assessment is a derived measurement with differential weight given to each component. The DAS28-ESR and DAS28-CRP was calculated at every visit within the clinical database in period 1. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment. The components of the DAS28 CRP score assessment were: Tender/Painful Joint Count (28); Swollen Joint Count (28), hsCRP, and the Subject General Health VAS assessment. This efficacy measurement was made at every study visit.

  • Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2 [ Time Frame: Baseline, Weeks 24, 28, 36, 44 and 52 ] [ Designated as safety issue: No ]
    The DAS assessment is a derived measurement with differential weight given to each component. The DAS28-ESR and DAS28-CRP was calculated at every visit within the clinical database in period 2. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment. The components of the DAS28 CRP score assessment were: Tender/Painful Joint Count (28); Swollen Joint Count (28), hsCRP, and the Subject General Health VAS assessment. This efficacy measurement was made at every study visit.

  • Percentage of Participants Who Had a Recurrence of Disease Symptoms During Period 2, Based on the Protocol Criteria [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Flare is defined as the criteria of loss of LDA plus ≥0.6 unit worsening in DAS28-ESR score during period 2.

  • Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1. [ Time Frame: Baseline, Weeks 4, 8, 16 and 24 ] [ Designated as safety issue: No ]
    EULAR response is based on DAS28-ESR scores. The following good and moderate response is defined based on DAS28-ESR at endpoint (DAS28-ESR improvement at from Baseline in parenthesis): ≤3.2 units (>1.2 units) is good response; ≤3.2 units (0.6-1.2 units) are moderate response; ≤3.2 units (≤0.6 units) are no response.

  • Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2. [ Time Frame: Baseline, Weeks 24, 28, 36, 44 and 52 ] [ Designated as safety issue: No ]
    EULAR response is based on DAS28-ESR scores. The following good and moderate response is defined based on DAS28-ESR at endpoint (DAS28-ESR improvement at from Baseline in parenthesis): ≤3.2 units (>1.2 units) is good response; ≤3.2 units (0.6-1.2 units) are moderate response; ≤3.2 units (≤0.6 units) are no response.

  • Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1. [ Time Frame: Baseline, Weeks 4, 8, 16 and 24 ] [ Designated as safety issue: No ]

    SDAI and CDAI are defined as:

    1) SDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0-28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) + hs CRP (in mg/dL) in Period 1. 2) CDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0 28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) in Period 1.


  • Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2. [ Time Frame: Baseline, Weeks 24, 28, 36, 44 and 52 ] [ Designated as safety issue: No ]

    SDAI and CDAI are defined as:

    1) SDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0-28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) + hs CRP (in mg/dL) in Period 2. 2) CDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0 28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) in Period 2.


  • Change of CDAI and SDAI at Each Visit During Period 1. [ Time Frame: Baseline, Weeks 4, 8, 16 and 24 ] [ Designated as safety issue: No ]

    SDAI and CDAI are defined as:

    1) SDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0-28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) + hs CRP (in mg/dL) in Period 1. 2) CDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0 28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) in Period 1.


  • Change of CDAI and SDAI at Each Visit During Period 2 [ Time Frame: Baseline, Weeks 24, 28, 36, 44 and 52 ] [ Designated as safety issue: No ]

    SDAI and CDAI are defined as:

    1) SDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0-28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) + hs CRP (in mg/dL) in Period 2. 2) CDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0 28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) in Period 2.


  • Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit. [ Time Frame: Baseline, Weeks 4, 8, 16 and 24 ] [ Designated as safety issue: No ]
    A 66 swollen and 68 tender joint count was used for calculating ACR responses. The ACR's definition for calculating improvement in RA (ACR20) was calculated as a 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: subject and physician global assessments of arthritis, pain, disability, and an acute phase reactant. Similarly, ACR50, ACR70 and ACR90 were calculated with the respective percent improvement. This efficacy measurement was made at every study visit.

  • Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit. [ Time Frame: Baseline, Weeks 24, 28, 36, 44 and 52 ] [ Designated as safety issue: No ]
    A 66 swollen and 68 tender joint count was used for calculating ACR responses. The ACR's definition for calculating improvement in RA (ACR20) was calculated as a 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: subject and physician global assessments of arthritis, pain, disability, and an acute phase reactant. Similarly, ACR50, ACR70 and ACR90 were calculated with the respective percent improvement. This efficacy measurement was made at every study visit.

  • Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts). [ Time Frame: Baseline, Weeks 4, 8, 16 and 24 ] [ Designated as safety issue: No ]
    A total of 66 swollen and 68 tender joints were assessed for tenderness/pain and swelling by the same qualified personnel (when possible) at each visit. For ACR responses, a 66/68 joint count was used. For DAS28-ESR, Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) calculations, the 28 joint count was used, which included: shoulders, elbows, wrists, metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, and knees.

  • Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts). [ Time Frame: Baseline, Weeks 24, 28, 36, 44 and 52 ] [ Designated as safety issue: No ]
    A total of 66 swollen and 68 tender joints were assessed for tenderness/pain and swelling by the same qualified personnel (when possible) at each visit. For ACR responses, a 66/68 joint count was used. For DAS28-ESR, Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) calculations, the 28 joint count was used, which included: shoulders, elbows, wrists, metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, and knees.

  • Change in the Physician Global Assessment of Arthritis at Each Visit During Period 1 [ Time Frame: Baseline, Weeks 4, 8, 16 and 24 ] [ Designated as safety issue: No ]
    The investigator estimated the subject's overall disease activity over the last 2 to 3 days (independent of the Subject Global Assessment of arthritis) using a scale between 0 (no disease activity) and 10 (extreme disease activity) and marking one number with an 'X'.

  • Change in the Physician Global Assessment of Arthritis at Each Visit During Period 2 [ Time Frame: Baseline, Weeks 24, 28, 36, 44 and 52 ] [ Designated as safety issue: No ]
    The investigator estimated the subject's overall disease activity over the last 2 to 3 days (independent of the Subject Global Assessment of arthritis) using a scale between 0 (no disease activity) and 10 (extreme disease activity) and marking one number with an 'X'.

  • Change in the Subject Global Assessment of Arthritis in Period 1 [ Time Frame: Baseline, Weeks 4, 8, 16 and 24 ] [ Designated as safety issue: No ]
    Subjects assessed their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity), which corresponded to the magnitude of their pain) and marked one number with an 'X'.

  • Change in the Subject Global Assessment of Arthritis in Period 2 [ Time Frame: Baseline, Weeks 24, 28, 36, 44 and 52 ] [ Designated as safety issue: No ]
    Subjects assessed their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity), which corresponded to the magnitude of their pain) and marked one number with an 'X'.

  • Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 1 [ Time Frame: Baseline, Weeks 4, 8, 16 and 24 ] [ Designated as safety issue: No ]
    Morning stiffness was defined as stiffness in and around the joints, lasting at least 1 hour before maximal improvement. Participants assessed their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity), which corresponded to the magnitude of their pain) and marked one number with an 'X'.

  • Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 2 [ Time Frame: Baseline, Weeks 24, 28, 36, 44 and 52 ] [ Designated as safety issue: No ]
    Morning stiffness was defined as stiffness in and around the joints, lasting at least 1 hour before maximal improvement. Participants assessed their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity), which corresponded to the magnitude of their pain) and marked one number with an 'X'.

  • Change in the Subject General Health Visual Analog Scale (VAS) and Pain VAS at Each Visit During Period 1 [ Time Frame: Baseline, Weeks 4, 8, 16 and 24 ] [ Designated as safety issue: No ]
    Participants were asked to answer the question "In general how would you rate your health over the last 2 3 weeks?" by marking a vertical line at the appropriate position through the 100 mm VAS. The length on the line was measured from the left (in mm). For Pain VAS, participants assessed the severity of their arthritis pain during the last 2 to 3 days using a 100 mm VAS by marking a vertical line at the appropriate position on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.

  • Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2 [ Time Frame: Baseline, Weeks 24, 28, 36, 44 and 52 ] [ Designated as safety issue: No ]
    Participants were asked to answer the question "In general how would you rate your health over the last 2-3 weeks?" by marking a vertical line at the appropriate position through the 100 mm VAS. The length on the line was measured from the left (in mm). For Pain VAS, participants assessed the severity of their arthritis pain during the last 2 to 3 days using a 100 mm VAS by marking a vertical line at the appropriate position on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.

  • Change in CRP and ESR at Each Visit During Period 1 [ Time Frame: Baseline, Weeks 4, 8, 16 and 24 ] [ Designated as safety issue: No ]
    The DAS assessment is a derived measurement with differential weight given to each component. The DAS28-ESR and DAS28-CRP was calculated at every visit within the clinical database in period 1. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment. The components of the DAS28 CRP score assessment were: Tender/Painful Joint Count (28); Swollen Joint Count (28), hsCRP, and the Subject General Health VAS assessment. This efficacy measurement was made at every study visit.

  • Change in CRP and ESR at Each Visit During Period 2 [ Time Frame: Baseline, Weeks 24, 28, 36, 44 and 52 ] [ Designated as safety issue: No ]
    The DAS assessment is a derived measurement with differential weight given to each component. The DAS28-ESR and DAS28-CRP was calculated at every visit within the clinical database in period 1. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment. The components of the DAS28 CRP score assessment were: Tender/Painful Joint Count (28); Swollen Joint Count (28), hsCRP, and the Subject General Health VAS assessment. This efficacy measurement was made at every study visit.


Enrollment: 491
Study Start Date: July 2012
Study Completion Date: March 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A Drug: Etanercept
etanercept 50mg once weekly + methotrexate with or without other DMARDs
Placebo Comparator: Group B Drug: placebo
etanercept placebo once weekly + methotrexate with or without other DMARDs

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject has a minimum 1 year history/diagnosis of rheumatoid arthritis based on the 1987 American College of Rheumatology (ACR) Revised criteria for RA.
  2. Subject must have active rheumatoid arthritis despite methotrexate (MTX) therapy of ≥10 mg/wk for at least 12 weeks. The MTX dose must be stable for at least 4 weeks immediately prior to screening.

Exclusion Criteria:

  1. Subjects who used any of the following systemic treatments during the washout periods given below:

    1. Oral corticosteroid dose of prednisone >7.5 mg/day (or equivalent) or a change in dose within 28 days of baseline.
    2. Treatment with more than 1 NSAID within 14 days at baseline.
    3. Methotrexate dose greater than 25 mg/week, or change in the dose of methotrexate within 28 days of baseline.
    4. Subjects will be allowed to continue the following non biologic DMARDs: sulfasalazine, hydroxychloroquine, and leflumomide. All other non-biologic DMARDs (including but not limited to gold, penicillamine, azathioprine, cyclophospamide), and biologic DMARDs must have been discontinued at least 2 months prior to Week 1.
    5. Any biologic B cell depleting agent (eg, rituximab) within 2 years of Week 1.
  2. Receipt of any live (attenuated) vaccine within 4 weeks prior to baseline.
  3. Receipt of any live (attenuated) vaccine within 4 weeks prior to baseline.
  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: NCT01578850

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Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01578850     History of Changes
Other Study ID Numbers: B1801315  2011-005448-87  B1801315 
Study First Received: April 12, 2012
Results First Received: February 16, 2016
Last Updated: May 25, 2016
Health Authority: South Africa: Medicines Control Council

Keywords provided by Pfizer:
rheumatoid arthritis
etanercept
methotrexate
DMARDs

Additional relevant MeSH terms:
Arthritis, Rheumatoid
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Etanercept
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2016