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
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Etanercept
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring rheumatoid arthritis, etanercept, methotrexate, DMARDs
Eligibility Criteria
Inclusion Criteria:
- Subject has a minimum 1 year history/diagnosis of rheumatoid arthritis based on the 1987 American College of Rheumatology (ACR) Revised criteria for RA.
- 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:
Subjects who used any of the following systemic treatments during the washout periods given below:
- Oral corticosteroid dose of prednisone >7.5 mg/day (or equivalent) or a change in dose within 28 days of baseline.
- Treatment with more than 1 NSAID within 14 days at baseline.
- Methotrexate dose greater than 25 mg/week, or change in the dose of methotrexate within 28 days of baseline.
- 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.
- Any biologic B cell depleting agent (eg, rituximab) within 2 years of Week 1.
- Receipt of any live (attenuated) vaccine within 4 weeks prior to baseline.
- Receipt of any live (attenuated) vaccine within 4 weeks prior to baseline.
Sites / Locations
- Hospital Santa Izabel - Santa Casa de Misericórdia da Bahia
- CIP (Centro Internacional de Pesquisa)
- CEPIC - Centro Paulista de Investigacao Clinica e Servicos Medicos LTDA
- Research Center
- Guangdong General Hospital
- Chinese Academy of Medical Sciences - Peking Union Medical C
- Shanghai Changning District Guanghua Hospital of Traditional Chinese and Western Medicine
- Shanghai Changhai Hospital[Rheumatology &Immunology]
- Centro Integral de reumatolo[Gerencia / Representante Legal]
- Fundacion Instituto de Reumatologia Fernando Chalem
- Hospital Pablo Tobon Uribe (HPTU)
- Revmatologicka poradna III. Interni nefrologicka, revmatologicka a endokrinologicka klinika
- Revmatologicky ustav
- Revmatologicka ambulance
- PV-Medical s.r.o.
- New University Hospital, Alexandria Clinical Research Center
- Al Azhar University Hospital [Rheumatology]
- Ain Shams University/Al Demerdash Hospital/Diabetology Unit
- Budai Irgalmasrendi Korhaz
- Magyar Honvédség Egészségügyi Központ
- Pharmaceutical Research Center- PRC. Jordan University of Science and Technology
- American University of Beirut Medical Center
- Queen Elizabeth Hospital
- Hopsital Putrajaya [Medicine]
- University Malaysia Medical Centre
- Centro de Investigación y Atención Integral de Durango, SC
- Centro de Alta Especialidad en Reumatología e Investigación
- Centro Medico Las Americas
- Hospital Central
- De La Salle University Health Sciences Campus- Clinical Epidemiology Unit
- St. Luke's Mecical Center
- Angeles University Foundation Medical Center
- Chong Hua Hospital, Medical Arts Center
- UP-Philippine General Hospital, Medical Research Laboratory, Medicine Department,
- Hamad Medical Corporation
- Spitalul Judetean
- Spitalul Clinic Judetean de Urgenta Brasov
- Spitalul Clinic de Recuperare
- Spitalul Clinic Judetean de Urgenta Targu Mures
- LLC Research Medical Complex Your Health based on City Clinical Hospital Number 7(Legal address)
- LLC Research Medical Complex Your Health based on City Clinical Hospital Number 7 (Actual address)
- Krasnoyarsk State Medical University named after Professor V.F. Voyno-Yasenetsky
- Krasnoyarsk State Medical University named after Professor V.F. Voyno-Yasenetsky,
- FSBSI "Scientific Research Institute of Rheumatology n. a. V.A. Nasonova"
- LLC Institute of Medical Trials (Actual address)
- Universitas Hospital [Cardiololgy]
- Vincent Pallotti Hospital
- Winelands Medical Research Centre
- Cathay General Hospital
- Buddhist Tzu Chi General Hospital - Dalin Branch
- China Medical University Hospital, Division of Rheumatology, Allergy and Immunology
- Taipei Medical University Hospital
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine,
- Siriraj Hospital [Rheumatology]
- Khon Kaen University (KKU) - Faculty of Medicine
- Songklanagarind Hospital
- Republican Clinical Hospital, Department of Internal Medicine #2 of Crimean State Medical University
- Komunalnyi zaklad Kyivskoi oblasnoi rady "Kyivska oblasna klinichna likarnia"
- Odessa Regional Clinical Hospital, Outpatient Department
- Municipal Institution of Ternopil Regional Council Ternopil University Hospital
- Vinnitsa Regional Clinical Hospital n.a. Pirogov, Department of Faculty Therapy of Vinnitsa NMU
- Al Baraha Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Group A
Group B
Arm Description
Outcomes
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.
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)
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
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
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
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
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
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
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
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.
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.
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.
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.
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.
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
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.
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.
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).
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).
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
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
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
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
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
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
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
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
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01578850
Brief Title
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
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)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
July 2012 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
March 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
rheumatoid arthritis, etanercept, methotrexate, DMARDs
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
491 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A
Arm Type
Experimental
Arm Title
Group B
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Etanercept
Intervention Description
etanercept 50mg once weekly + methotrexate with or without other DMARDs
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
etanercept placebo once weekly + methotrexate with or without other DMARDs
Primary Outcome Measure Information:
Title
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.
Description
Proportion of participants who remained in LDA DAS28-ESR <3.2 at Week 52 is presented below.
Time Frame
Baseline and Week 52
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Remained in Remission at Week 52 (DAS28-ESR)
Description
Proportion of participants who remained in Remission (DAS28-ESR <2.6) at Week 52.
Time Frame
Baseline and Week 52
Title
Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-C-reactive Protein [CRP]) at Each Visit During Period 1
Description
Proportion of participants who achieved LDA (DAS28-ESR and DAS28-CRP at each visit during period 1 is presented below.
Time Frame
Baseline, Weeks 4, 8, 16 and 24
Title
Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2
Description
Proportion of participants who achieved LDA (DAS28-ESR and DAS28-CRP at each visit during period 2 is presented below.
Time Frame
Baseline, Weeks 24, 28, 36, 44 and 52
Title
Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 1
Description
Proportion of participants who achieved remission (DAS28-ESR and DAS28-CRP at each visit during period 1 is presented below.
Time Frame
Baseline, Weeks 4, 8, 16 and 24
Title
Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2
Description
Proportion of participants who achieved LDA (DAS28-ESR and DAS28-CRP at each visit during period 2 is presented below.
Time Frame
Baseline, Weeks 24, 28, 36, 44 and 52
Title
Change From Baseline in DAS28-CRP and DAS28-ESR in Period 1
Description
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.
Time Frame
Baseline, Weeks 4, 8, 16 and 24
Title
Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2
Description
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.
Time Frame
Baseline, Weeks 24, 28, 36, 44 and 52
Title
Percentage of Participants Who Had a Recurrence of Disease Symptoms During Period 2, Based on the Protocol Criteria
Description
Flare is defined as the criteria of loss of LDA plus ≥0.6 unit worsening in DAS28-ESR score during period 2.
Time Frame
Baseline and Week 52
Title
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.
Description
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.
Time Frame
Baseline, Weeks 4, 8, 16 and 24
Title
Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.
Description
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.
Time Frame
Baseline, Weeks 24, 28, 36, 44 and 52
Title
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.
Description
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.
Time Frame
Baseline, Weeks 4, 8, 16 and 24
Title
Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.
Description
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.
Time Frame
Baseline, Weeks 24, 28, 36, 44 and 52
Title
Change of CDAI and SDAI at Each Visit During Period 1.
Description
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.
Time Frame
Baseline, Weeks 4, 8, 16 and 24
Title
Change of CDAI and SDAI at Each Visit During Period 2
Description
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.
Time Frame
Baseline, Weeks 24, 28, 36, 44 and 52
Title
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.
Description
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.
Time Frame
Baseline, Weeks 4, 8, 16 and 24
Title
Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.
Description
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.
Time Frame
Baseline, Weeks 24, 28, 36, 44 and 52
Title
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).
Description
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.
Time Frame
Baseline, Weeks 4, 8, 16 and 24
Title
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).
Description
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.
Time Frame
Baseline, Weeks 24, 28, 36, 44 and 52
Title
Change in the Physician Global Assessment of Arthritis at Each Visit During Period 1
Description
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'.
Time Frame
Baseline, Weeks 4, 8, 16 and 24
Title
Change in the Physician Global Assessment of Arthritis at Each Visit During Period 2
Description
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'.
Time Frame
Baseline, Weeks 24, 28, 36, 44 and 52
Title
Change in the Subject Global Assessment of Arthritis in Period 1
Description
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'.
Time Frame
Baseline, Weeks 4, 8, 16 and 24
Title
Change in the Subject Global Assessment of Arthritis in Period 2
Description
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'.
Time Frame
Baseline, Weeks 24, 28, 36, 44 and 52
Title
Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 1
Description
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'.
Time Frame
Baseline, Weeks 4, 8, 16 and 24
Title
Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 2
Description
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'.
Time Frame
Baseline, Weeks 24, 28, 36, 44 and 52
Title
Change in the Subject General Health Visual Analog Scale (VAS) and Pain VAS at Each Visit During Period 1
Description
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.
Time Frame
Baseline, Weeks 4, 8, 16 and 24
Title
Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2
Description
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.
Time Frame
Baseline, Weeks 24, 28, 36, 44 and 52
Title
Change in CRP and ESR at Each Visit During Period 1
Description
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.
Time Frame
Baseline, Weeks 4, 8, 16 and 24
Title
Change in CRP and ESR at Each Visit During Period 2
Description
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.
Time Frame
Baseline, Weeks 24, 28, 36, 44 and 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject has a minimum 1 year history/diagnosis of rheumatoid arthritis based on the 1987 American College of Rheumatology (ACR) Revised criteria for RA.
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:
Subjects who used any of the following systemic treatments during the washout periods given below:
Oral corticosteroid dose of prednisone >7.5 mg/day (or equivalent) or a change in dose within 28 days of baseline.
Treatment with more than 1 NSAID within 14 days at baseline.
Methotrexate dose greater than 25 mg/week, or change in the dose of methotrexate within 28 days of baseline.
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.
Any biologic B cell depleting agent (eg, rituximab) within 2 years of Week 1.
Receipt of any live (attenuated) vaccine within 4 weeks prior to baseline.
Receipt of any live (attenuated) vaccine within 4 weeks prior to baseline.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Hospital Santa Izabel - Santa Casa de Misericórdia da Bahia
City
Salvador
State/Province
Bahia
ZIP/Postal Code
40050-410
Country
Brazil
Facility Name
CIP (Centro Internacional de Pesquisa)
City
Goiania
State/Province
Goiás
ZIP/Postal Code
74110-120
Country
Brazil
Facility Name
CEPIC - Centro Paulista de Investigacao Clinica e Servicos Medicos LTDA
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
04209-003
Country
Brazil
Facility Name
Research Center
City
Juiz de Fora
Country
Brazil
Facility Name
Guangdong General Hospital
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China
Facility Name
Chinese Academy of Medical Sciences - Peking Union Medical C
City
Beijing
ZIP/Postal Code
100050
Country
China
Facility Name
Shanghai Changning District Guanghua Hospital of Traditional Chinese and Western Medicine
City
Shanghai
ZIP/Postal Code
200052
Country
China
Facility Name
Shanghai Changhai Hospital[Rheumatology &Immunology]
City
Shanghai
ZIP/Postal Code
200433
Country
China
Facility Name
Centro Integral de reumatolo[Gerencia / Representante Legal]
City
Barranquilla
State/Province
Atlántico
ZIP/Postal Code
99999
Country
Colombia
Facility Name
Fundacion Instituto de Reumatologia Fernando Chalem
City
Bogota DC
State/Province
Cundinamarca
Country
Colombia
Facility Name
Hospital Pablo Tobon Uribe (HPTU)
City
Antioquia
Country
Colombia
Facility Name
Revmatologicka poradna III. Interni nefrologicka, revmatologicka a endokrinologicka klinika
City
Olomouc
ZIP/Postal Code
775 20
Country
Czech Republic
Facility Name
Revmatologicky ustav
City
Praha 2
ZIP/Postal Code
12850
Country
Czech Republic
Facility Name
Revmatologicka ambulance
City
Praha 5
ZIP/Postal Code
150 06
Country
Czech Republic
Facility Name
PV-Medical s.r.o.
City
Zlin
ZIP/Postal Code
760 01
Country
Czech Republic
Facility Name
New University Hospital, Alexandria Clinical Research Center
City
Alexandria
State/Province
Al Iskandariyah
ZIP/Postal Code
21131
Country
Egypt
Facility Name
Al Azhar University Hospital [Rheumatology]
City
Cairo
State/Province
Al Qahirah
ZIP/Postal Code
12111
Country
Egypt
Facility Name
Ain Shams University/Al Demerdash Hospital/Diabetology Unit
City
Cairo
Country
Egypt
Facility Name
Budai Irgalmasrendi Korhaz
City
Budapest
ZIP/Postal Code
1023
Country
Hungary
Facility Name
Magyar Honvédség Egészségügyi Központ
City
Budapest
ZIP/Postal Code
1062
Country
Hungary
Facility Name
Pharmaceutical Research Center- PRC. Jordan University of Science and Technology
City
Irbid
ZIP/Postal Code
22110
Country
Jordan
Facility Name
American University of Beirut Medical Center
City
Beirut
ZIP/Postal Code
1107-2020
Country
Lebanon
Facility Name
Queen Elizabeth Hospital
City
Kota Kinabalu
State/Province
Sabah
ZIP/Postal Code
88586
Country
Malaysia
Facility Name
Hopsital Putrajaya [Medicine]
City
Putrajaya
State/Province
Wilayah Persekutuan Putrajaya
ZIP/Postal Code
62250
Country
Malaysia
Facility Name
University Malaysia Medical Centre
City
Kuala Lumpur
ZIP/Postal Code
59100
Country
Malaysia
Facility Name
Centro de Investigación y Atención Integral de Durango, SC
City
Durango
State/Province
Durango / Mexico
ZIP/Postal Code
34080
Country
Mexico
Facility Name
Centro de Alta Especialidad en Reumatología e Investigación
City
San Luis de Potosi
State/Province
San Luis Potosí / Mexico
ZIP/Postal Code
78213
Country
Mexico
Facility Name
Centro Medico Las Americas
City
Merida
State/Province
Yucatan
Country
Mexico
Facility Name
Hospital Central
City
San Luis Potosi
ZIP/Postal Code
78290
Country
Mexico
Facility Name
De La Salle University Health Sciences Campus- Clinical Epidemiology Unit
City
Dasmarinas
State/Province
Cavite
ZIP/Postal Code
4114
Country
Philippines
Facility Name
St. Luke's Mecical Center
City
Quezon
State/Province
Manila
ZIP/Postal Code
1102
Country
Philippines
Facility Name
Angeles University Foundation Medical Center
City
Angeles City
State/Province
Pampanga
Country
Philippines
Facility Name
Chong Hua Hospital, Medical Arts Center
City
Cebu City
ZIP/Postal Code
6000
Country
Philippines
Facility Name
UP-Philippine General Hospital, Medical Research Laboratory, Medicine Department,
City
Manila
ZIP/Postal Code
1000
Country
Philippines
Facility Name
Hamad Medical Corporation
City
Doha
ZIP/Postal Code
3050
Country
Qatar
Facility Name
Spitalul Judetean
City
Baia Mare
State/Province
Maramure
ZIP/Postal Code
4800
Country
Romania
Facility Name
Spitalul Clinic Judetean de Urgenta Brasov
City
Brasov
ZIP/Postal Code
500365
Country
Romania
Facility Name
Spitalul Clinic de Recuperare
City
Iasi
ZIP/Postal Code
700656
Country
Romania
Facility Name
Spitalul Clinic Judetean de Urgenta Targu Mures
City
Tg Mures
ZIP/Postal Code
540136
Country
Romania
Facility Name
LLC Research Medical Complex Your Health based on City Clinical Hospital Number 7(Legal address)
City
Kazan
ZIP/Postal Code
420097
Country
Russian Federation
Facility Name
LLC Research Medical Complex Your Health based on City Clinical Hospital Number 7 (Actual address)
City
Kazan
ZIP/Postal Code
420137
Country
Russian Federation
Facility Name
Krasnoyarsk State Medical University named after Professor V.F. Voyno-Yasenetsky
City
Krasnoyarsk
ZIP/Postal Code
660014
Country
Russian Federation
Facility Name
Krasnoyarsk State Medical University named after Professor V.F. Voyno-Yasenetsky,
City
Krasnoyarsk
ZIP/Postal Code
660022
Country
Russian Federation
Facility Name
FSBSI "Scientific Research Institute of Rheumatology n. a. V.A. Nasonova"
City
Moscow
ZIP/Postal Code
115522
Country
Russian Federation
Facility Name
LLC Institute of Medical Trials (Actual address)
City
St. Petersburg
ZIP/Postal Code
196084
Country
Russian Federation
Facility Name
Universitas Hospital [Cardiololgy]
City
Bloemfontein
State/Province
Free State
ZIP/Postal Code
9301
Country
South Africa
Facility Name
Vincent Pallotti Hospital
City
Cape Town
ZIP/Postal Code
7405
Country
South Africa
Facility Name
Winelands Medical Research Centre
City
Stellenbosch
ZIP/Postal Code
7600
Country
South Africa
Facility Name
Cathay General Hospital
City
Taiwan
State/Province
Taoyuan
ZIP/Postal Code
330
Country
Taiwan
Facility Name
Buddhist Tzu Chi General Hospital - Dalin Branch
City
Chia-Yi
ZIP/Postal Code
62247
Country
Taiwan
Facility Name
China Medical University Hospital, Division of Rheumatology, Allergy and Immunology
City
Taichung
ZIP/Postal Code
404
Country
Taiwan
Facility Name
Taipei Medical University Hospital
City
Taipei
ZIP/Postal Code
11042
Country
Taiwan
Facility Name
Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine,
City
Amphoe Mueang
State/Province
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand
Facility Name
Siriraj Hospital [Rheumatology]
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Khon Kaen University (KKU) - Faculty of Medicine
City
Khon Kaen
ZIP/Postal Code
40002
Country
Thailand
Facility Name
Songklanagarind Hospital
City
Songkla
ZIP/Postal Code
90110
Country
Thailand
Facility Name
Republican Clinical Hospital, Department of Internal Medicine #2 of Crimean State Medical University
City
Simferopol
State/Province
Crimea
ZIP/Postal Code
95017
Country
Ukraine
Facility Name
Komunalnyi zaklad Kyivskoi oblasnoi rady "Kyivska oblasna klinichna likarnia"
City
Kyiv
ZIP/Postal Code
04107
Country
Ukraine
Facility Name
Odessa Regional Clinical Hospital, Outpatient Department
City
Odessa
ZIP/Postal Code
65025
Country
Ukraine
Facility Name
Municipal Institution of Ternopil Regional Council Ternopil University Hospital
City
Ternopil
ZIP/Postal Code
46000
Country
Ukraine
Facility Name
Vinnitsa Regional Clinical Hospital n.a. Pirogov, Department of Faculty Therapy of Vinnitsa NMU
City
Vinnitsa
ZIP/Postal Code
21018
Country
Ukraine
Facility Name
Al Baraha Hospital
City
Dubai
Country
United Arab Emirates
12. IPD Sharing Statement
Citations:
PubMed Identifier
31277720
Citation
Tanaka Y, Smolen JS, Jones H, Szumski A, Marshall L, Emery P. The effect of deep or sustained remission on maintenance of remission after dose reduction or withdrawal of etanercept in patients with rheumatoid arthritis. Arthritis Res Ther. 2019 Jul 5;21(1):164. doi: 10.1186/s13075-019-1937-4.
Results Reference
derived
PubMed Identifier
30200078
Citation
Zerbini CAF, Abud-Mendoza C, Mendez-Patarroyo P, De Angelo Andrade M, Pedersen R, Vlahos B, Borlenghi CE. Maintenance of low disease activity and remission with etanercept-disease-modifying antirheumatic drug (DMARD) combination therapy compared with treatment with DMARDs alone in Latin American patients with active rheumatoid arthritis: Subset analysis of a randomized trial. Medicine (Baltimore). 2018 Sep;97(36):e11989. doi: 10.1097/MD.0000000000011989.
Results Reference
derived
PubMed Identifier
28597306
Citation
Pavelka K, Akkoc N, Al-Maini M, Zerbini CAF, Karateev DE, Nasonov EL, Rahman MU, Pedersen R, Dinh A, Shen Q, Vasilescu R, Kotak S, Mahgoub E, Vlahos B. Maintenance of remission with combination etanercept-DMARD therapy versus DMARDs alone in active rheumatoid arthritis: results of an international treat-to-target study conducted in regions with limited biologic access. Rheumatol Int. 2017 Sep;37(9):1469-1479. doi: 10.1007/s00296-017-3749-7. Epub 2017 Jun 9.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1801315&StudyName=Study%20conducted%20in%20subjects%20with%20rheumatoid%20arthritis%20who%20have%20moderate%20to%20severe%20disease%20activity%20despite%20methotrexate%20therapy%20with%20or%20
Description
To obtain contact information for a study center near you, click here.
Learn more about this trial
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
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