A Study Of PF-06410293 (Adalimumab-Pfizer) And Adalimumab (Humira®) In Combination With Methotrexate In Subjects With Active Rheumatoid Arthritis (REFLECTIONS B538-02).
- Conditions
- Rheumatoid Arthritis
- Interventions
- Biological: PF-06410293Biological: Adalimumab
- Registration Number
- NCT02480153
- Lead Sponsor
- Pfizer
- Brief Summary
The study will assess the efficacy, safety, and immunogenicity of PF-06410293 and adalimumab in combination with methotrexate in subjects with moderately to severly active rheumatoid arthritis who have had an inadequate response to methotrexate.
In an additional optional portion of the study, during open label Treatment Period 3 (TP3), a subset of subjects used a Prefilled Pen (PFP) to administer up to 3 injections of their study treatment (PF-06410293) at home.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 597
- Diagnosis of rheumatoid arthritis based on 2010 ACR/EULAR criteria for at least 4 months.
- At least 6 tender (of 68 assessed) and 6 swollen (of 66 assessed) joints at screening and baseline.
- Hs-CRP equal or greater than 8 mg/L.
- Must have received methotrexate for at least 12 weeks and been on a stable dose for at least 4 weeks prior to the first study dose.
- Evidence of untreated or inadequately treated latent or active TB.
- Evidence of uncontrolled, clinically significant diseases, including moderate or severe heart failure (NYHA Class III/IV) or malignancy in the previous 5 years.
- History of infection requiring hospitalization or parenteral antimicrobial therapy within 6 months prior to first dose of study drug.
- May have received no more than 2 doses of one biologic therapy (other than adalimumab or lymphocyte depleting therapy).
- Any second DMARD must be washed out prior to the first study dose.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PF-06410293 PF-06410293 - Adalimumab Adalimumab -
- Primary Outcome Measures
Name Time Method Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12: Period 1 Week 12 ACR20 is a categorical variable indicating a 20% or greater improvement in tender and swollen joint counts and 20% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
- Secondary Outcome Measures
Name Time Method Number of Participants With an American College of Rheumatology 50% (ACR50) Response: Period 1 Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) ACR50 is a categorical variable indicating a 50% or greater improvement in tender and swollen joint counts and 50% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Other Time Points Other Than Week 12: Period 1 Weeks 2, 4, 6, 8, 18 and 26 (pre-dose) ACR20 is a categorical variable indicating a 20% or greater improvement in tender and swollen joint counts and 20% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
Number of Participants With an American College of Rheumatology 70% (ACR70) Response: Period 1 Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) ACR70 is a categorical variable indicating a 70% or greater improvement in tender and swollen joint counts and 70% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
Number of Participants With an American College of Rheumatology 20% (ACR20) Response: Period 2 Weeks 26, 30, 36, 44 and 52 (pre-dose) ACR20 is a categorical variable indicating a 20% or greater improvement in tender and swollen joint counts and 20% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
Change From Baseline in Tender Joint Count: Period 2 Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose) Sixty-eight (68) joints were assessed by an independent blinded joint assessor to determine the number of joints that were considered tender. The 68 joints assessed were: upper body including temporomandibular, sternoclavicular, acromioclavicular; upper extremity including shoulder, elbow, wrist (radiocarpal, carpal and carpometacarpal considered as 1 unit), metacarpophalangeals (MCP I, II, III, IV, V), thumb interphalangeal, proximal interphalangeals (PIP II, III, IV, V), and distal interphalangeals (DIP II, III, IV, V); lower extremity including hip, knee, ankle, tarsus (subtalar, transverse tarsal and tarsometatarsal considered as 1 unit), metatarsophalangeals (MTP I, II, III, IV, V), great toe interphalangeal, proximal and distal interphalangeals combined (PIP and DIP II, III, IV, V).
Number of Participants With an American College of Rheumatology 20% (ACR20) Response: Period 3 Weeks 52, 56, 66, 76 and 78 ACR20 is a categorical variable indicating a 20% or greater improvement in tender and swollen joint counts and 20% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
Number of Participants With an American College of Rheumatology 50% (ACR50) Response: Period 3 Weeks 52, 56, 66, 76 and 78 ACR50 is a categorical variable indicating a 50% or greater improvement in tender and swollen joint counts and 50% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
Change From Baseline in Tender Joint Count: Period 3 Baseline, Weeks 52, 56, 66, 76 and 78 Sixty-eight (68) joints were assessed by an independent blinded joint assessor to determine the number of joints that were considered tender. The 68 joints assessed were: upper body including temporomandibular, sternoclavicular, acromioclavicular; upper extremity including shoulder, elbow, wrist (radiocarpal, carpal and carpometacarpal considered as 1 unit), metacarpophalangeals (MCP I, II, III, IV, V), thumb interphalangeal, proximal interphalangeals (PIP II, III, IV, V), and distal interphalangeals (DIP II, III, IV, V); lower extremity including hip, knee, ankle, tarsus (subtalar, transverse tarsal and tarsometatarsal considered as 1 unit), metatarsophalangeals (MTP I, II, III, IV, V), great toe interphalangeal, proximal and distal interphalangeals combined (PIP and DIP II, III, IV, V).
Number of Participants With an American College of Rheumatology 50% (ACR50) Response: Period 2 Weeks 26, 30, 36, 44 and 52 (pre-dose) ACR50 is a categorical variable indicating a 50% or greater improvement in tender and swollen joint counts and 50% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
Change From Baseline in Swollen Joint Count: Period 3 Baseline, Weeks 52, 56, 66, 76 and 78 Sixty-six (66) joints were assessed for swelling, the same as those listed for tender joint count, excluding the right and left hip joints.
Change From Baseline in Swollen Joint Count: Period 1 Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) Sixty-six (66) joints were assessed for swelling, the same as those listed for tender joint count, excluding the right and left hip joints.
Change From Baseline in Patient's Assessment of Arthritis Pain (PAAP): Period 2 Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose) Participants assessed the severity of their arthritis pain using a 100 mm Visual Analog Scale (VAS) by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.
Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP): Period 1 Baseline, Weeks1, 2, 4, 6, 8, 12, 18 and 26 (pre-dose) Serum samples were analyzed to determine the level of hs-CRP, which was an acute-phase reactant.
Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP): Period 2 Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose) Serum samples were analyzed to determine the level of hs-CRP, which was an acute-phase reactant.
Number of Participants With an American College of Rheumatology 70% (ACR70) Response: Period 2 Weeks 26, 30, 36, 44 and 52 (pre-dose) ACR70 is a categorical variable indicating a 70% or greater improvement in tender and swollen joint counts and 70% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
Number of Participants With an American College of Rheumatology 70% (ACR70) Response: Period 3 Weeks 52, 56, 66, 76 and 78 ACR70 is a categorical variable indicating a 70% or greater improvement in tender and swollen joint counts and 70% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
Change From Baseline in Tender Joint Count: Period 1 Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) Sixty-eight (68) joints were assessed by an independent blinded joint assessor to determine the number of joints that were considered tender. The 68 joints assessed were: upper body including temporomandibular, sternoclavicular, acromioclavicular; upper extremity including shoulder, elbow, wrist (radiocarpal, carpal and carpometacarpal considered as 1 unit), metacarpophalangeals (MCP I, II, III, IV, V), thumb interphalangeal, proximal interphalangeals (PIP II, III, IV, V), and distal interphalangeals (DIP II, III, IV, V); lower extremity including hip, knee, ankle, tarsus (subtalar, transverse tarsal and tarsometatarsal considered as 1 unit), metatarsophalangeals (MTP I, II, III, IV, V), great toe interphalangeal, proximal and distal interphalangeals combined (PIP and DIP II, III, IV, V).
Change From Baseline in Swollen Joint Count: Period 2 Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose) Sixty-six (66) joints were assessed for swelling, the same as those listed for tender joint count, excluding the right and left hip joints.
Change From Baseline in Physician's Global Assessment of Arthritis (PGAA): Period 2 Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose) The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This was an evaluation based on the participant's disease symptoms, functional capacity and physical examination, and independent of the participant's reported assessments of PGA (patient's global assessment of arthritis) and PAAP (patient's assessment of arthritis pain). The investigator's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "None" and the 100 mm end labeled "Extreme".
Change From Baseline in Patient's Assessment of Arthritis Pain (PAAP): Period 3 Baseline, Weeks 52, 56, 66, 76 and 78 Participants assessed the severity of their arthritis pain using a 100 mm Visual Analog Scale (VAS) by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.
Change From Baseline in Physician's Global Assessment of Arthritis (PGAA): Period 3 Baseline, Weeks 52, 56, 66, 76 and 78 The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This was an evaluation based on the participant's disease symptoms, functional capacity and physical examination, and independent of the participant's reported assessments of PGA (patient's global assessment of arthritis) and PAAP (patient's assessment of arthritis pain). The investigator's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "None" and the 100 mm end labeled "Extreme".
Change From Baseline in Patient's Global Assessment of Arthritis (PGA): Period 2 Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose) Participants answered the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" The participant's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "Very Well" and the 100 mm end labeled "Very Poorly".
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI): Period 1 Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) HAQ-DI assesses the degree of difficulty a participant had experienced during the past week in 8 domains of daily activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each activity category consisted of 2-3 items. For each question in the questionnaire, the level of difficulty was scored from 0 to 3 with 0 representing "no difficulty", 1 as "some difficulty", 2 as "much difficulty", and 3 as "unable to do". Any activity that required assistance from another individual or required the use of an assistive device would adjust to a minimum score of 2 to represent a more limited functional status. Overall score was computed as the sum of scores divided by the number of domains answered. Total possible score range was 0-3 with 0 representing "no difficulty", 1 as "some difficulty", 2 as "much difficulty", and 3 as "unable to do". Higher score indicate more difficulty in performing daily living activities.
Change From Baseline in Physician's Global Assessment of Arthritis (PGAA): Period 1 Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This was an evaluation based on the participant's disease symptoms, functional capacity and physical examination, and independent of the participant's reported assessments of PGA (patient's global assessment of arthritis) and PAAP (patient's assessment of arthritis pain). The investigator's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "None" and the 100 mm end labeled "Extreme".
Change From Baseline in Patient's Assessment of Arthritis Pain (PAAP): Period 1 Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) Participants assessed the severity of their arthritis pain using a 100 mm Visual Analog Scale (VAS) by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.
Change From Baseline in Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]): Period 2 Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose) The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient's global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP \[mg/L\] +1) + 0.014 (PGA \[mm\]) + 0.96. Higher score indicate more disease activity. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L).
Number of Participants Achieving Disease Activity Score Remission (DAS <2.6): Period 1 Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient's global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP \[mg/L\] +1) + 0.014 (PGA \[mm\]) + 0.96. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L). Higher score indicate more disease activity; DAS28-4 (CRP) \<2.6 indicates remission.
Change From Baseline in Patient's Global Assessment of Arthritis (PGA): Period 1 Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) Participants answered the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" The participant's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "Very Well" and the 100 mm end labeled "Very Poorly".
Change From Baseline in Patient's Global Assessment of Arthritis (PGA): Period 3 Baseline, Weeks 52, 56, 66, 76 and 78 Participants answered the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" The participant's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "Very Well" and the 100 mm end labeled "Very Poorly".
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI): Period 2 Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose) HAQ-DI assesses the degree of difficulty a participant had experienced during the past week in 8 domains of daily activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each activity category consisted of 2-3 items. For each question in the questionnaire, the level of difficulty was scored from 0 to 3 with 0 representing "no difficulty", 1 as "some difficulty", 2 as "much difficulty", and 3 as "unable to do". Any activity that required assistance from another individual or required the use of an assistive device would adjust to a minimum score of 2 to represent a more limited functional status. Overall score was computed as the sum of scores divided by the number of domains answered. Total possible score range was 0-3 with 0 representing "no difficulty", 1 as "some difficulty", 2 as "much difficulty", and 3 as "unable to do". Higher score indicate more difficulty in performing daily living activities.
Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP): Period 3 Baseline, Weeks 52, 56, 66, 76 and 78 Serum samples were analyzed to determine the level of hs-CRP, which was an acute-phase reactant.
Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb): Period 2 Week 26 dosing up to Week 52 (pre-dose) Serum samples were analyzed for the presence or absence of ADA using a semi-quantitative electrochemiluminescent (ECL) assay, and ADA positive was defined as ADA titer \>=1.88. Serum samples tested positive for ADA were further analyzed for the presence or absence of NAb using a semi-quantitative cell-based assay, and NAb positive was defined as NAb titer \>=0.70.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI): Period 3 Baseline, Weeks 52, 56, 66, 76 and 78 HAQ-DI assesses the degree of difficulty a participant had experienced during the past week in 8 domains of daily activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each activity category consisted of 2-3 items. For each question in the questionnaire, the level of difficulty was scored from 0 to 3 with 0 representing "no difficulty", 1 as "some difficulty", 2 as "much difficulty", and 3 as "unable to do". Any activity that required assistance from another individual or required the use of an assistive device would adjust to a minimum score of 2 to represent a more limited functional status. Overall score was computed as the sum of scores divided by the number of domains answered. Total possible score range was 0-3 with 0 representing "no difficulty", 1 as "some difficulty", 2 as "much difficulty", and 3 as "unable to do". Higher score indicate more difficulty in performing daily living activities.
Change From Baseline in Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]): Period 3 Baseline, Weeks 52, 56, 66, 76 and 78 The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient's global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP \[mg/L\] +1) + 0.014 (PGA \[mm\]) + 0.96. Higher score indicate more disease activity. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L).
Number of Participants Achieving European League Against Rheumatism (EULAR) Response: Period 2 Weeks 26, 30, 36, 44 and 52 (pre-dose) EULAR response was based on DAS28 EULAR response criteria. Good response was achieved if DAS28 improvement from baseline \>1.2 and DAS28 =\<3.2. Moderate response was achieved if DAS28 improvement from baseline \>0.6 to =\<1.2 and DAS28 =\<5.1; or DAS improvement from baseline \>1.2 and DAS28 \>3.2. No response was achieved if DAS improvement from baseline =\<0.6 (no matter present DAS28 score); or DAS improvement from baseline \>0.6 to =\<1.2 and DAS28 \>5.1.
Number of Participants Achieving European League Against Rheumatism (EULAR) Response: Period 3 Weeks 52, 56, 66, 76 and 78 EULAR response was based on DAS28 EULAR response criteria. Good response was achieved if DAS28 improvement from baseline \>1.2 and DAS28 =\<3.2. Moderate response was achieved if DAS28 improvement from baseline \>0.6 to =\<1.2 and DAS28 =\<5.1; or DAS improvement from baseline \>1.2 and DAS28 \>3.2. No response was achieved if DAS improvement from baseline =\<0.6 (no matter present DAS28 score); or DAS improvement from baseline \>0.6 to =\<1.2 and DAS28 \>5.1.
Number of Participants Achieving American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Response: Period 2 Weeks 26, 30, 36, 44 and 52 (pre-dose) Participants were considered to be in ACR/EULAR remission when either of the following criteria was met: scores on the tender joint count, swollen joint count, hs-CRP (mg/dL) and PGA (0-10 cm scale) were all =\<1; or the score on the simplified disease activity index (SDAI) was =\<3.3. SDAI score was the sum of tender joint count (28), swollen joint count (28), PGA (0-10 cm scale), physician's global assessment of arthritis (PGAA, 0-10 cm scale) and hs-CRP (mg/dL).
Serum Concentration Versus Time Summary: Period 1 Pre-dose on Days 1, 15, 43, 85 and 183, and at any time during Day 8 visit Serum Concentration Versus Time Summary: Period 2 Pre-dose on Days 183, 211, 253 and 365 Change From Baseline in Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]): Period 1 Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient's global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP \[mg/L\] +1) + 0.014 (PGA \[mm\]) + 0.96. Higher score indicate more disease activity. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L).
Number of Participants Achieving European League Against Rheumatism (EULAR) Response: Period 1 Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) EULAR response was based on DAS28 EULAR response criteria. Good response was achieved if DAS28 improvement from baseline \>1.2 and DAS28 =\<3.2. Moderate response was achieved if DAS28 improvement from baseline \>0.6 to =\<1.2 and DAS28 =\<5.1; or DAS improvement from baseline \>1.2 and DAS28 \>3.2. No response was achieved if DAS improvement from baseline =\<0.6 (no matter present DAS28 score); or DAS improvement from baseline \>0.6 to =\<1.2 and DAS28 \>5.1.
Number of Participants Achieving American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Response：Period 1 Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) Participants were considered to be in ACR/EULAR remission when either of the following criteria was met: scores on the tender joint count, swollen joint count, hs-CRP (mg/dL) and PGA (0-10 cm scale) were all =\<1; or the score on the simplified disease activity index (SDAI) was =\<3.3. SDAI score was the sum of tender joint count (28), swollen joint count (28), PGA (0-10 cm scale), physician's global assessment of arthritis (PGAA, 0-10 cm scale) and hs-CRP (mg/dL).
Number of Participants Achieving American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Response: Period 3 Weeks 52, 56, 66, 76 and 78 Participants were considered to be in ACR/EULAR remission when either of the following criteria was met: scores on the tender joint count, swollen joint count, hs-CRP (mg/dL) and PGA (0-10 cm scale) were all =\<1; or the score on the simplified disease activity index (SDAI) was =\<3.3. SDAI score was the sum of tender joint count (28), swollen joint count (28), PGA (0-10 cm scale), physician's global assessment of arthritis (PGAA, 0-10 cm scale) and hs-CRP (mg/dL).
Number of Participants With Laboratory Abnormalities: Period 2 Week 26 dosing up to Week 52 (pre-dose) Laboratory evaluation included hematology, clinical chemistry, and urinalysis. Each parameter was evaluated against commonly used and widely accepted criteria. Number of participants with any laboratory abnormality during Period 2 (without regard to baseline abnormality) is presented.
Number of Participants Achieving Disease Activity Score Remission (DAS <2.6): Period 2 Weeks 26, 30, 36, 44 and 52 (pre-dose) The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient's global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP \[mg/L\] +1) + 0.014 (PGA \[mm\]) + 0.96. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L). Higher score indicate more disease activity; DAS28-4 (CRP) \<2.6 indicates remission.
Number of Participants Achieving Disease Activity Score Remission (DAS <2.6): Period 3 Weeks 52, 56, 66, 76 and 78 The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient's global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP \[mg/L\] +1) + 0.014 (PGA \[mm\]) + 0.96. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L). Higher score indicate more disease activity; DAS28-4 (CRP) \<2.6 indicates remission.
Serum Concentration Versus Time Summary: Period 3 Pre-dose on Days 365, 393, 463, 547 and 575 Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb): Period 1 Baseline up to Week 26 (pre-dose) Serum samples were analyzed for the presence or absence of ADA using a semi-quantitative electrochemiluminescent (ECL) assay, and ADA positive was defined as ADA titer \>=1.88. Serum samples tested positive for ADA were further analyzed for the presence or absence of NAb using a semi-quantitative cell-based assay, and NAb positive was defined as NAb titer \>=0.70.
Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb): Period 3 Week 52 dosing up to follow-up visit (Week 92) Serum samples were analyzed for the presence or absence of ADA using a semi-quantitative electrochemiluminescent (ECL) assay, and ADA positive was defined as ADA titer \>=1.88. Serum samples tested positive for ADA were further analyzed for the presence or absence of NAb using a semi-quantitative cell-based assay, and NAb positive was defined as NAb titer \>=0.70.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 3 Week 52 dosing up to follow-up visit (Week 92) An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs for Period 3 were events between first dose of study drug in Period 3 and up to Week 92 visit that were absent before treatment or that worsened relative to prior state. Treatment-related TEAE was any untoward medical occurrence attributed to study drug. AEs included both serious and non-serious AEs.
Number of Participants With Laboratory Abnormalities: Period 1 Baseline (Day 1) up to Week 26 (pre-dose) Laboratory evaluation included hematology, clinical chemistry, and urinalysis. Each parameter was evaluated against commonly used and widely accepted criteria. Number of participants with any laboratory abnormality during Period 1 (without regard to baseline abnormality) is presented.
Number of Participants With Laboratory Abnormalities: Period 3 Week 52 dosing up to follow-up visit (Week 92) Laboratory evaluation included hematology, clinical chemistry, and urinalysis. Each parameter was evaluated against commonly used and widely accepted criteria. Number of participants with any laboratory abnormality during Period 3 (without regard to baseline abnormality) is presented.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 1 Baseline (Day 1) up to Week 26 (pre-dose) An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs for Period 1 were events between first dose of study drug in Period 1 and up to Week 26 pre-dose assessments that were absent before treatment or that worsened relative to pre-treatment state. Treatment-related TEAE was any untoward medical occurrence attributed to study drug. AEs included both serious and non-serious AEs.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 2 Week 26 dosing up to Week 52 (pre-dose) An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs for Period 2 were events between first dose of study drug in Period 2 and up to Week 52 pre-dose assessments that were absent before treatment or that worsened relative to prior state. Treatment-related TEAE was any untoward medical occurrence attributed to study drug. AEs included both serious and non-serious AEs.
Trial Locations
- Locations (182)
Robert W. Levin, MD, PA
🇺🇸Clearwater, Florida, United States
Charlotte Maxeke Johannesburg Academic Hospital
🇿🇦Johannesburg, Gauteng, South Africa
SIMED Arthritis Center
🇺🇸Gainesville, Florida, United States
Manhattan Medical Research
🇺🇸New York, New York, United States
Sarasota Arthritis Research Center
🇺🇸Sarasota, Florida, United States
Physicians East PA
🇺🇸Greenville, North Carolina, United States
Physician's Clinic of Iowa, P.C.
🇺🇸Cedar Rapids, Iowa, United States
Buffalo Rheumatology and Medicine PLLC
🇺🇸Orchard Park, New York, United States
Indian River Primary Care
🇺🇸Vero Beach, Florida, United States
Graves-Gilbert Clinic Bowling Green
🇺🇸Bowling Green, Kentucky, United States
Regional Health Clinical Research
🇺🇸Rapid City, South Dakota, United States
Arthritis, Rheumatic & Back Disease Associates, P.A.
🇺🇸Voorhees, New Jersey, United States
Low Country Rheumatology, PA
🇺🇸Charleston, South Carolina, United States
Altoona Center for Clinical Research
🇺🇸Duncansville, Pennsylvania, United States
Rheumatology and Pulmonary Clinic
🇺🇸Beckley, West Virginia, United States
Lekarna Vesalion
🇨🇿Ostrava, Czechia
UMHAT "Sv. Ivan Rilski" EAD
🇧🇬Sofia, Bulgaria
Inland Rheumatology Clinical Trials, Inc.
🇺🇸Upland, California, United States
Revmatologicky ustav
🇨🇿Praha 2, Czechia
Southeastern Integrated Medical, PL, d/b/a Florida Medical Research
🇺🇸Gainesville, Florida, United States
Lekarna Hradebni s.r.o.
🇨🇿Uherske Hradiste, Czechia
St Luke's Intermountain Research Center
🇺🇸Boise, Idaho, United States
Desert Valley Medical Group
🇺🇸Victorville, California, United States
Alastair C. Kennedy, MD
🇺🇸Vero Beach, Florida, United States
Sapporo City General Hospital
🇯🇵Sapporo, Hokkaido, Japan
LSMUL Kauno klinikos
🇱🇹Kaunas, Lithuania
Vilniaus universiteto ligonines Santariskiu klinikos
🇱🇹Vilnius, Lithuania
Regional Medical Clinic - Rheumatology
🇺🇸Rapid City, South Dakota, United States
Anjo Kosei Hospital
🇯🇵Anjo-shi, Aichi, Japan
University Multiprofile Hospital for Active Treatment "Sv. Ivan Rilski" EAD
🇧🇬Sofia, Bulgaria
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Revmatologie Bruntal, s.r.o.
🇨🇿Bruntal, Czechia
Hirose Clinic
🇯🇵Tokorozawa, Saitama, Japan
CCBR-SYNARC, a.s.
🇨🇿Pardubice, Czechia
Klinikum der Universität München
🇩🇪München, Germany
Praxiszentrum St. Bonifatius
🇩🇪München, Germany
Fundacion Instituto de Reumatologia Fernando Chalem
🇨🇴Bogota, Colombia
Austin Regional Clinic
🇺🇸Austin, Texas, United States
Matsubara Mayflower Hospital
🇯🇵Kato, Hyogo, Japan
Amarillo Center for Clinical Research, Ltd.
🇺🇸Amarillo, Texas, United States
MHAT Plovdiv AD
🇧🇬Plovdiv, Bulgaria
Benu Lekarna
🇨🇿Pardubice, Czechia
Lekarna Na vrsku
🇨🇿Bruntal, Czechia
National Hospital Organization Asahikawa Medical Center
🇯🇵Asahikawa, Hokkaido, Japan
MEDICAL PLUS, s.r.o.
🇨🇿Uherske Hradiste, Czechia
University Multiprofile Hospital for Active Treatment (UMHAT) Kaspela EOOD
🇧🇬Plovdiv, Bulgaria
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
West Tennessee Research Institute
🇺🇸Jackson, Tennessee, United States
National Hospital Organization Nagasaki Medical Center
🇯🇵Omura, Nagasaki, Japan
Ramesh C Gupta, M.D.
🇺🇸Memphis, Tennessee, United States
Qualiclinic Kft.
🇭🇺Budapest, Hungary
Vital Medical Center Orvosi es Fogorvosi Kozpont
🇭🇺Veszprem, Hungary
L.K.N. Arthrocentrum, s.r.o.
🇨🇿Hlucin, Czechia
Gemeinschaftspraxis Dr. von Hinüber/Dr. Demary
🇩🇪Hildesheim, Germany
Kondo clinic for rheumatism and orthopaedics
🇯🇵Fukuoka, Japan
Hanyang University Seoul Hospital
🇰🇷Seoul, Korea, Republic of
JSC Medical Corporation Evex
🇬🇪Tbilisi, Georgia
Rheumazentrum Ratingen
🇩🇪Ratingen, Germany
Hokkaido University Hospital
🇯🇵Sapporo, Hokkaido, Japan
National Hospital Organization Kyushu Medical Center
🇯🇵Fukuoka, Japan
Rheumapraxis Dr. Martin Welcker und Kollegen
🇩🇪Planegg, Germany
Debreceni Egyetem Klinikai Központ
🇭🇺Debrecen, Hajdú-bihar, Hungary
MedLab
🇳🇿Timaru, South Canterbury, New Zealand
LTD Israeli-Georgian Medical Research Clinic Helsicore"
🇬🇪Tbilisi, Georgia
Hospital Universitario A Coruña
🇪🇸A Coruña, Spain
GUZ " Regional clinical hospital"
🇷🇺Saratov, Russian Federation
Knappschaftsklinikum Saar GmbH
🇩🇪Püttlingen, Germany
Inoue Hospital
🇯🇵Takasaki, Gunma, Japan
Regional Clinical Hospital
🇷🇺Orenburg, Russian Federation
Katayama Orthopaedic Rheumatology Clinic
🇯🇵Asahikawa, Hokkaido, Japan
Timaru Hospital
🇳🇿Timaru, South Canterbury, New Zealand
ABK REUMA SRL-Medicentro Biociencias Peru SRL
🇵🇪Lima, Peru
China Medical University Hospital
🇨🇳Taichung, Taiwan
Hospital Universitario de Fuenlabrada
🇪🇸Fuenlabrada, Madrid, Spain
GBU of Ryazan region Regional clinical cardiology dispanser
🇷🇺Ryazan, Russian Federation
GBUZ Republican hospital n.a. V.A. Baranov
🇷🇺Petrozavodsk, Republic OF Karelia, Russian Federation
Konkuk University Medical Center
🇰🇷Seoul, Korea, Republic of
Waikato Hospital
🇳🇿Hamilton, New Zealand
Hospital Infanta Luisa
🇪🇸Sevilla, Spain
LLC Alliance Biomedical Ural group
🇷🇺Izhevsk, Russian Federation
GMU Kursk Regional Clinical Hospital of the Healthcare Committee of the Kursk Region
🇷🇺Kursk, Russian Federation
Unidad de Investigacion en Medicina Interna y Enfermedades Criticas
🇵🇪Arequipa, Peru
Wellington Hospital, Capital Coast District Health Board
🇳🇿Wellington, New Zealand
Arrowe Park Hospital, Wirral University Teaching Hospitals NHS Foundation Trust
🇬🇧Wirral, Merseyside, United Kingdom
Hospital Universitario Cruces
🇪🇸Barakaldo, Vizcaya, Spain
Clinresco Centres (Pty) Ltd
🇿🇦Kempton Park, Gauteng, South Africa
GAUZ of Kemerovo Region "Regional clinical hospital for war veterans"
🇷🇺Kemerovo, Russian Federation
Centro de Investigación para el Estudio de Enfermedades Reumáticas
🇵🇪Lima, Peru
Orenburg State Medical Academy
🇷🇺Orenburg, Russian Federation
GBKUZ of Yaroslavl region "City hospital n. a. N.A. Semashko"
🇷🇺Yaroslavl, Russian Federation
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Chung Shan Medical University Hospital
🇨🇳Taichung, Taiwan
Lvivskyi oblasnyi klinichnyi diahnostychnyi tsentr,
🇺🇦Lviv, Ukraine
St. Augustine's Hospital
🇿🇦Durban, Kwa-zulu Natal, South Africa
Cincinnati Rheumatic Disease Study Group, Inc.
🇺🇸Cincinnati, Ohio, United States
The Clinical Research Institute of Houston, LLC
🇺🇸Houston, Texas, United States
V.Tsitlanadze Scientifically-Practical Rheumatology Center LTD
🇬🇪Tbilisi, Georgia
Chonnam National University Hospital
🇰🇷Gwangju, Korea, Republic of
East Tallinn Central Hospital
🇪🇪Tallinn, Estonia
LTD Cardio-Reanimation Center
🇬🇪Tbilisi, Georgia
Klaipedos universitetine ligonine
🇱🇹Klaipeda, Lithuania
LTD "Unimed Adjara"
🇬🇪Batumi, Ajaria, Georgia
LTD.MediClubGeorgia
🇬🇪Tbilisi, Georgia
Consultorio Medico Privado de Reumatologia
🇲🇽Mexicali, BAJA California, Mexico
V.Tsitlanadze Scientifically-Practical Rheumatology Center
🇬🇪Tbilisi, Georgia
Oficina administrativa
🇵🇪Arequipa, Arequipa, Peru
Oficina Administrativa
🇵🇪Lima, Lima, Peru
Komunalnyi zaklad okhorony zdorovia "Kharkivska miska klinichna likarnia #8"
🇺🇦M. Kharkiv, Ukraine
Military Medical Academy,
🇷🇸Belgrade, Serbia
Institute for Treatment and Rehabilitation Niska Banja
🇷🇸Niska Banja, Serbia
Special Hospital for Rheumatic Diseases Novi Sad
🇷🇸Novi Sad, Serbia
Taipei Medical University Hospital
🇨🇳Taipei, Taiwan
Arizona Arthritis & Rheumatology Associates, PC
🇺🇸Phoenix, Arizona, United States
Saitama Medical Center
🇯🇵Kawagoe, Saitama, Japan
Municipal Clinical Hospital No. 1 Named after N.I. Pirogov
🇷🇺Moscow, Russian Federation
GBOU VPO Ryazan State Medical University Named after Academician I.P. Pavlov
🇷🇺Ryazan, Russian Federation
GBUZ VO Regional clinical hospital
🇷🇺Vladimir, Russian Federation
ArthroCare, Arthritis Care & Research P.C.
🇺🇸Gilbert, Arizona, United States
St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare
🇺🇸Fullerton, California, United States
Arthritis and Rheumatic Disease Specialties
🇺🇸Aventura, Florida, United States
East Bay Rheumatology Medical Group, Inc.
🇺🇸San Leandro, California, United States
Westlake Medical Research
🇺🇸Thousand Oaks, California, United States
Javed Rheumatology Associates, Inc
🇺🇸Newark, Delaware, United States
Rheumatology Associates of Central Florida, P.A.
🇺🇸Orlando, Florida, United States
The Center for Rheumatology and Bone Research
🇺🇸Wheaton, Maryland, United States
Bronson Internal Medicine and Rheumatology
🇺🇸Battle Creek, Michigan, United States
North Mississippi Medical Clinics, Inc. - Clinical Research
🇺🇸Tupelo, Mississippi, United States
Physician Research Collaboration, LLC
🇺🇸Lincoln, Nebraska, United States
Westroads Clinical Research, Inc.
🇺🇸Omaha, Nebraska, United States
Metroplex Clinical Research Center
🇺🇸Dallas, Texas, United States
Southwest Rheumatology Research, LLC
🇺🇸Mesquite, Texas, United States
Center for Arthritis and Rheumatic Diseases, P.C.
🇺🇸Chesapeake, Virginia, United States
Wenatchee Valley Hospitals & Clinics
🇺🇸Wenatchee, Washington, United States
Paradise Arthritis & Rheumatology Pty Ltd
🇦🇺Southport, Queensland, Australia
The Queen Elizabeth Hospital
🇦🇺Woodville South, South Australia, Australia
EDUMED Educação em Saúde S/S Ltda
🇧🇷Curitiba, Paraná, Brazil
Innomedica OÜ
🇪🇪Tallinn, Estonia
Unimedi Kakheti Ltd, Telavi Referral Hospital
🇬🇪Telavi, Kakheti, Georgia
Tbilisi Heart and Vascular Clinic LTD
🇬🇪Tbilisi, Georgia
Timaru Rheumatology Studies
🇳🇿Timaru, South Canterbury, New Zealand
Synexus Polska Sp. z o.o. Oddzial w Katowicach
🇵🇱Katowice, Poland
Spb GBUZ "Clinical rheumatology hospital # 25" City CDC prevention of osteoporosis
🇷🇺Saint-Petersburg, Russian Federation
Kyivska miska klinichna likarnia #6
🇺🇦Kyiv, Ukraine
Komunalna 4-a miska klinichna likarnia m. Lvova,
🇺🇦Lviv, Ukraine
Komunalnyi zaklad Kyivskoi oblasnoi rady "Kyivska oblasna klinichna likarnia",
🇺🇦M. Kyiv,, Ukraine
Bahatoprofilnyi medychnyi tsentr (Universytetska klinika #1)
🇺🇦Odesa, Ukraine
Komunalnyi zaklad Sumskoi oblasnoi rady "Sumska oblasna klinichna
🇺🇦Sumy, Ukraine
Vinnytska oblasna klinichna likarnia im. M.I.Pyrohova revmatolohichne viddilennia
🇺🇦Vinnytsia, Ukraine
Komunalna ustanova "Zaporizka oblasna klinichna likarnia" Zaporizkoi oblasnoi rady
🇺🇦Zaporizhzhia, Ukraine
Royal United Hospital Bath NHS Foundation Trust ,Royal National Hospital for Rheumatic Diseases
🇬🇧Bath, Somerset, United Kingdom
The Leeds Institute of Rheumatic and Musculoskeletal Medicine
🇬🇧Leeds, WEST Yorkshire, United Kingdom
Centrum Medyczne AMED
🇵🇱Warszawa, Poland
LTD Altravita
🇬🇪Tbilisi, Georgia
Consultorio de Reumatologia
🇲🇽Ciudad de Mexico, Mexico
Clinica Medica Cayetano Heredia
🇵🇪Lima, Peru
Instituto de Ginecología y Reproducción & Cirugía Mínimamente Invasiva
🇵🇪Lima, Peru
Institute of Rheumatology
🇷🇸Belgrade, Serbia
Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust
🇬🇧Basingstoke, Hampshire, United Kingdom
Arthritis Clinical Research Trials, Dr. C.E Spargo and Dr. R.B Bhorat Practice
🇿🇦Cape Town, Western CAPE, South Africa
Panorama Medical Centre
🇿🇦Cape Town, Western CAPE, South Africa
NZOZ Zdrowie Osteo-Medic s.c.
🇵🇱Bialystok, Poland
NZOZ Centrum Reumatologiczne Indywidualna Specjalistyczna Praktyka Lekarska Lek. med. Barbara Bazela
🇵🇱Elblag, Poland
Synexus Polska Sp. z o.o. Oddzial w Gdyni
🇵🇱Gdynia, Poland
MTZ Clinical Research Sp. z o.o.
🇵🇱Warszawa, Poland
Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk
🇵🇱Bialystok, Poland
Prywatna Praktyka Lekarska Prof. UM Dr Hab. Med. Pawel Hrycaj
🇵🇱Poznan, Poland
Synexus Polska Sp. z o.o. Oddział we Wroclawiu
🇵🇱Wroclaw, Poland
Centrum Kliniczno-Badawcze J.Brzezicki, B. Gornikiewicz-Brzezicka Lekarze Spolka Partnerska
🇵🇱Elblag, Poland
Centrum Medyczne Pratia Katowice
🇵🇱Katowice, Poland
Zespol Poradni Specjalistycznych "REUMED" Filia nr 2
🇵🇱Lublin, Poland
NZOZ Lecznica MAK-MED. S.C.
🇵🇱Nadarzyn, Poland
Synexus Polska Sp. z o.o. Oddzial w Warszawie
🇵🇱Warszawa, Poland
''Rheuma Medicus'' Zakład Opieki Zdrowotnej
🇵🇱Warszawa, Poland
Niepubliczny Zaklad Opieki Zdrowotnej ''Nasz Lekarz''
🇵🇱Torun, Poland
St Luke' s Clinic
🇺🇸Meridian, Idaho, United States
Clinical Research of Reading, LLC
🇺🇸Wyomissing, Pennsylvania, United States
Northwest Diagnostic Clinic, PA
🇺🇸Shenandoah, Texas, United States
RK Will Pty Ltd
🇦🇺Victoria Park, Western Australia, Australia
International Medical Research
🇺🇸Daytona Beach, Florida, United States
Accurate Clinical Research
🇺🇸League City, Texas, United States
Schlosspark-Klinik
🇩🇪Berlin, Germany
GBUZ of city of Moscow City clinical hospital n.a. A.K.Eramishantsev of Ministry of Healthcare of
🇷🇺Moscow, Russian Federation