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
- Registration Number
- NCT01578850
- Lead Sponsor
- Pfizer
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 491
- 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.
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A Etanercept - Group B placebo -
- Primary Outcome Measures
Name Time Method 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. Baseline and Week 52 Proportion of participants who remained in LDA DAS28-ESR \<3.2 at Week 52 is presented below.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Who Remained in Remission at Week 52 (DAS28-ESR) Baseline and Week 52 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 Baseline, Weeks 4, 8, 16 and 24 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 Baseline, Weeks 24, 28, 36, 44 and 52 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 Baseline, Weeks 4, 8, 16 and 24 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 Baseline, Weeks 24, 28, 36, 44 and 52 Proportion of participants who achieved LDA (DAS28-ESR and DAS28-CRP at each visit during period 2 is presented below.
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. Baseline, Weeks 4, 8, 16 and 24 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.
Change in the Subject Global Assessment of Arthritis in Period 1 Baseline, Weeks 4, 8, 16 and 24 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 Baseline, Weeks 4, 8, 16 and 24 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 Baseline, Weeks 24, 28, 36, 44 and 52 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 From Baseline in DAS28-CRP and DAS28-ESR in Period 1 Baseline, Weeks 4, 8, 16 and 24 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 Baseline, Weeks 24, 28, 36, 44 and 52 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.
Change of CDAI and SDAI at Each Visit During Period 1. Baseline, Weeks 4, 8, 16 and 24 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 American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit. Baseline, Weeks 4, 8, 16 and 24 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. Baseline, Weeks 24, 28, 36, 44 and 52 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 2 (Using 28 Joint Count as Well as 66/68 Joint Counts). Baseline, Weeks 24, 28, 36, 44 and 52 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 Subject General Health VAS and Pain VAS at Each Visit During Period 2 Baseline, Weeks 24, 28, 36, 44 and 52 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.
Percentage of Participants Who Had a Recurrence of Disease Symptoms During Period 2, Based on the Protocol Criteria Baseline and Week 52 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 EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2. Baseline, Weeks 24, 28, 36, 44 and 52 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. Baseline, Weeks 4, 8, 16 and 24 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. Baseline, Weeks 24, 28, 36, 44 and 52 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 2 Baseline, Weeks 24, 28, 36, 44 and 52 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 in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts). Baseline, Weeks 4, 8, 16 and 24 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 2 Baseline, Weeks 24, 28, 36, 44 and 52 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 1 Baseline, Weeks 4, 8, 16 and 24 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 General Health Visual Analog Scale (VAS) and Pain VAS at Each Visit During Period 1 Baseline, Weeks 4, 8, 16 and 24 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 Global Assessment of Arthritis in Period 2 Baseline, Weeks 24, 28, 36, 44 and 52 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 CRP and ESR at Each Visit During Period 2 Baseline, Weeks 24, 28, 36, 44 and 52 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 1 Baseline, Weeks 4, 8, 16 and 24 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.
Trial Locations
- Locations (62)
PV-Medical s.r.o.
🇨🇿Zlin, Czech Republic
Ain Shams University/Al Demerdash Hospital/Diabetology Unit
🇪🇬Cairo, Egypt
New University Hospital, Alexandria Clinical Research Center
🇪🇬Alexandria, Al Iskandariyah, Egypt
Fundacion Instituto de Reumatologia Fernando Chalem
🇨🇴Bogota DC, Cundinamarca, Colombia
Revmatologicky ustav
🇨🇿Praha 2, Czech Republic
Centro de Investigación y Atención Integral de Durango, SC
🇲🇽Durango, Durango / Mexico, Mexico
Hospital Central
🇲🇽San Luis Potosi, Mexico
Research Center
🇧🇷Juiz de Fora, Brazil
Winelands Medical Research Centre
🇿🇦Stellenbosch, South Africa
Revmatologicka poradna III. Interni nefrologicka, revmatologicka a endokrinologicka klinika
🇨🇿Olomouc, Czech Republic
De La Salle University Health Sciences Campus- Clinical Epidemiology Unit
🇵🇭Dasmarinas, Cavite, Philippines
Chong Hua Hospital, Medical Arts Center
🇵🇭Cebu City, Philippines
Al Azhar University Hospital [Rheumatology]
🇪🇬Cairo, Al Qahirah, Egypt
Hopsital Putrajaya [Medicine]
🇲🇾Putrajaya, Wilayah Persekutuan Putrajaya, Malaysia
FSBSI "Scientific Research Institute of Rheumatology n. a. V.A. Nasonova"
🇷🇺Moscow, Russian Federation
Vincent Pallotti Hospital
🇿🇦Cape Town, South Africa
LLC Research Medical Complex Your Health based on City Clinical Hospital Number 7(Legal address)
🇷🇺Kazan, Russian Federation
Budai Irgalmasrendi Korhaz
🇭🇺Budapest, Hungary
Krasnoyarsk State Medical University named after Professor V.F. Voyno-Yasenetsky
🇷🇺Krasnoyarsk, Russian Federation
Spitalul Clinic Judetean de Urgenta Targu Mures
🇷🇴Tg Mures, Romania
Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine,
🇹🇭Amphoe Mueang, Chiang Mai, Thailand
Republican Clinical Hospital, Department of Internal Medicine #2 of Crimean State Medical University
🇺🇦Simferopol, Crimea, Ukraine
Odessa Regional Clinical Hospital, Outpatient Department
🇺🇦Odessa, Ukraine
Krasnoyarsk State Medical University named after Professor V.F. Voyno-Yasenetsky,
🇷🇺Krasnoyarsk, Russian Federation
Universitas Hospital [Cardiololgy]
🇿🇦Bloemfontein, Free State, South Africa
Songklanagarind Hospital
🇹🇭Songkla, Thailand
Komunalnyi zaklad Kyivskoi oblasnoi rady "Kyivska oblasna klinichna likarnia"
🇺🇦Kyiv, Ukraine
Hospital Santa Izabel - Santa Casa de Misericórdia da Bahia
🇧🇷Salvador, Bahia, Brazil
Cathay General Hospital
🇨🇳Taiwan, Taoyuan, Taiwan
Shanghai Changning District Guanghua Hospital of Traditional Chinese and Western Medicine
🇨🇳Shanghai, China
Shanghai Changhai Hospital[Rheumatology &Immunology]
🇨🇳Shanghai, China
Guangdong General Hospital
🇨🇳Guangzhou, Guangdong, China
Revmatologicka ambulance
🇨🇿Praha 5, Czech Republic
University Malaysia Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Centro Medico Las Americas
🇲🇽Merida, Yucatan, Mexico
Centro Integral de reumatolo[Gerencia / Representante Legal]
🇨🇴Barranquilla, Atlántico, Colombia
Pharmaceutical Research Center- PRC. Jordan University of Science and Technology
🇯🇴Irbid, Jordan
Angeles University Foundation Medical Center
🇵🇭Angeles City, Pampanga, Philippines
CIP (Centro Internacional de Pesquisa)
🇧🇷Goiania, Goiás, Brazil
UP-Philippine General Hospital, Medical Research Laboratory, Medicine Department,
🇵🇭Manila, Philippines
Hamad Medical Corporation
🇶🇦Doha, Qatar
Spitalul Clinic de Recuperare
🇷🇴Iasi, Romania
Al Baraha Hospital
🇦🇪Dubai, United Arab Emirates
Hospital Pablo Tobon Uribe (HPTU)
🇨🇴Antioquia, Colombia
Khon Kaen University (KKU) - Faculty of Medicine
🇹🇭Khon Kaen, Thailand
Taipei Medical University Hospital
🇨🇳Taipei, Taiwan
LLC Institute of Medical Trials (Actual address)
🇷🇺St. Petersburg, Russian Federation
Chinese Academy of Medical Sciences - Peking Union Medical C
🇨🇳Beijing, China
CEPIC - Centro Paulista de Investigacao Clinica e Servicos Medicos LTDA
🇧🇷Sao Paulo, SP, Brazil
American University of Beirut Medical Center
🇱🇧Beirut, Lebanon
Magyar Honvédség Egészségügyi Központ
🇭🇺Budapest, Hungary
Queen Elizabeth Hospital
🇲🇾Kota Kinabalu, Sabah, Malaysia
St. Luke's Mecical Center
🇵🇭Quezon, Manila, Philippines
Centro de Alta Especialidad en Reumatología e Investigación
🇲🇽San Luis de Potosi, San Luis Potosí / Mexico, Mexico
Spitalul Clinic Judetean de Urgenta Brasov
🇷🇴Brasov, Romania
Spitalul Judetean
🇷🇴Baia Mare, Maramure, Romania
Buddhist Tzu Chi General Hospital - Dalin Branch
🇨🇳Chia-Yi, Taiwan
China Medical University Hospital, Division of Rheumatology, Allergy and Immunology
🇨🇳Taichung, Taiwan
Siriraj Hospital [Rheumatology]
🇹🇭Bangkok, Thailand
Municipal Institution of Ternopil Regional Council Ternopil University Hospital
🇺🇦Ternopil, Ukraine
LLC Research Medical Complex Your Health based on City Clinical Hospital Number 7 (Actual address)
🇷🇺Kazan, Russian Federation
Vinnitsa Regional Clinical Hospital n.a. Pirogov, Department of Faculty Therapy of Vinnitsa NMU
🇺🇦Vinnitsa, Ukraine