Rheumatoid Arthritis Extension Trial For Subjects Who Have Participated In Other PF-05280586 Trials (REFLECTIONS B328-04)

Not Applicable

Completed

Conditions: Rheumatoid Arthritis

Interventions: Biological: Rituximab-US + Rituximab-Pfizer x 2 Courses
Biological: Rituximab-Pfizer (PF-05280586) x 3 courses
Biological: Rituximab-EU+ Rituximab-Pfizer x 2 Courses

Registration Number: NCT01643928

Lead Sponsor: Pfizer

Brief Summary: This extension study will evaluate the safety (including immunogenicity) of treatment with rituximab-Pfizer, as well as the safety and immunogenicity after transitioning from rituximab-US or rituximab-EU to rituximab-Pfizer. This study will provide continued treatment access to subjects with active rheumatoid arthritis who have participated for at least 16 weeks in other studies in the rituximab Pfizer program.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 185

Inclusion Criteria

Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Participated for a minimum of 16 weeks after the initiation of the last course of treatment in a previous rheumatoid arthritis study in the rituximab-Pfizer program within the past 2 months.

Exclusion Criteria

Investigational site staff members or relatives of those site staff members or subjects who are Pfizer employees directly involved in the conduct of the study.
Initiated treatment with investigational agents or other biologics (including Rituxan and MabThera) since participating in a previous rheumatoid arthritis study in the rituximab-Pfizer program.

Study & Design

Study Type: INTERVENTIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Rituximab-US+Rituximab-Pfizer	Rituximab-US + Rituximab-Pfizer x 2 Courses	Subjects will receive Rituximab-US x 1 course followed by Rituximab-Pfizer x 2 courses.
Rituximab-Pfizer	Rituximab-Pfizer (PF-05280586) x 3 courses	-
Rituximab-EU+Rituximab-Pfizer	Rituximab-EU+ Rituximab-Pfizer x 2 Courses	Subjects will receive Rituximab-EU x 1 course followed by Rituximab-Pfizer x 2 courses.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With American College of Rheumatology (ACR) 70% Improvement (ACR70) Response - by the End of Course 1	Week 1, 6, 13, and 25 (Course 1).	ACR70 response: ≥70% improvement in tender/painful joint count; ≥70% improvement in swollen joint count; and ≥70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the HAQ); and CRP.
Percentage of Participants by Anti-Drug Antibody (ADA) Status Using Anti-PF-05280586 Antibody Assay	Course 1 (C1) Overall, Course 2 (C2) Overall, Course 3 (C3) Overall, and All Courses Overall.	Serum samples were collected to determine the presence of ADA using two validated assays, one specific for PF-05280586 and one specific for the licensed drug products. For participants assigned to PF-05280586 in Study B3281001, blood samples were screened for ADA using the assay specific to PF-05280586; if the blood samples were confirmed to be positive (+ve) for ADA against PF-05280586, the samples were also analyzed using the assay specific for the licensed drug products to assess cross-reactivity of the ADA. For participants assigned to the licensed products in Study B3281001, blood samples were screened for ADA using both assays in order to assess any product-specific ADA and/or cross-reactivity for the transition from the licensed products to PF-05280586.
Percentage of Participants by Neutralizing Antibody (Nab) Status in Participants With a Positive ADA Using Anti-PF-05280586 NAb Assay	Weeks 1, 3, 13, and 25 (Course 1, Course 2, and Course 3).	Blood samples that were confirmed as positive for ADA were further evaluated for Nab using validated assays - None of the ADA samples tested positive for NAb.
Percentage of Participants by ADA Status Using Anti-Rituximab Antibody Assay	Course 1 Overall, Course 2 Overall, Course 3 Overall, and All Courses Overall.	Serum samples were collected to determine the presence of ADA using two validated assays, one specific for PF-05280586 and one specific for the licensed drug products. For participants assigned to PF-05280586 in Study B3281001, blood samples were screened for ADA using the assay specific to PF-05280586; if the blood samples were confirmed to be positive for ADA against PF-05280586, the samples were also analyzed using the assay specific for the licensed drug products to assess cross-reactivity of the ADA. For participants assigned to the licensed products in Study B3281001, blood samples were screened for ADA using both assays in order to assess any product-specific ADA and/or cross-reactivity for the transition from the licensed products to PF-05280586.
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Swollen Joint Count - by the End of Course 1	Screening, Week 1, 6, 13, and 25 (Course 1).	Sixty-six joints were assessed by a blinded joint assessor for swelling. For consistency, a single assessor was preferred to perform all evaluations across the study for an individual participant. The response was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not be assessed.
Percentage of Participants by Nab Status in Participants With a Positive ADA Using Anti-PF-05280586 NAb Assay Using Anti-Rituximab NAb Assay	Weeks 1, 3, 13, and 25 (Course 1, Course 2, and Course 3).	Blood samples that were confirmed as positive for ADA were further evaluated for Nab using validated assays. - None of the ADA samples tested positive for NAb.
Mean Change From Initial Study Baseline in Disease Activity Score (DAS28)-C-Reactive Protein (CRP) - by the End of Course 3	Baseline B3281001, Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).	The disease activity score (DAS) assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis Visual Analog Scale (VAS). The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP equals (=) 0.56 square root (sqrt) (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 natural log \[ln\] (CRP \[milligrams per liter, mg/L\] +1) + 0.014 (global assessment of health \[GH\]) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity.
Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on DAS28 - by the End of Course 1	Week 1, 6, 13, and 25 (Course 1).	The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline greater than (\>) 1.2 with present DAS28 less than or equal to (≤) 3.2; moderate responders had a change from baseline \>0.6 and ≤1.2 with present DAS28 ≤3.2 or change from baseline \>0.6 with present DAS28 \>3.2 and ≤5.1 or change from baseline \>1.2 with present DAS28 \>5.1; non-responders had a change from baseline ≤0.6 with present DAS28 ≤5.1 or change from baseline ≤1.2 with present DAS28 \>5.1.
Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on DAS28 - by the End of Course 2	Week 1, 6, 13, and 25 (Course 1 and Course 2).	The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline greater than (\>) 1.2 with present DAS28 less than or equal to (≤) 3.2; moderate responders had a change from baseline \>0.6 and ≤1.2 with present DAS28 ≤3.2 or change from baseline \>0.6 with present DAS28 \>3.2 and ≤5.1 or change from baseline \>1.2 with present DAS28 \>5.1; non-responders had a change from baseline ≤0.6 with present DAS28 ≤5.1 or change from baseline ≤1.2 with present DAS28 \>5.1.
Percentage of Participants With American College of Rheumatology (ACR) 50% Improvement (ACR50) Response - by the End of Course 2	Week 1, 6, 13, and 25 (Course 1 and Course 2).	ACR50 response: ≥50% improvement in tender/painful joint count; ≥50% improvement in swollen joint count; and ≥50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the HAQ); and CRP.
Mean Rituximab Serum Trough Concentrations	Weeks 1, 3, 13, and 25 (Course 1, Course 2, and Course 3), Follow up Months 3, 6, 9, and 12. Course 3/Week 25 is End of Treatment (EOT).	Serum samples for determination of drug concentrations were collected pre-dose concurrent with ADA sample collection. Drug concentrations in the samples were determined using a validated assay.
Circulating Immunoglobulin G (IgG) Concentrations	Screening, Week 25 (Course 1), and Weeks 1 and 25 (Course 2 and Course 3).	Blood samples for immunoglobulin assessments were obtained to determine IgG levels in serum.
Circulating Immunoglobulin M (IgM) Concentrations	Screening, Week 25 (Course 1), and Weeks 1 and 25 (Course 2 and Course 3).	Blood samples for immunoglobulin assessments were obtained to determine IgM levels in serum.
Anti-Cyclic Citrullinated Peptide (Anti-CCP) and Complement	Week 1 and 25 (Course 1, Course 2, and Course 3).	Blood samples were obtained to determine anti-CCP and compliment levels in serum.
Percentage of Participants With Low Disease Activity State (LDAS) (≤3.2) - by the End of Course 1	Week 1, 6, 13, and 25 (Course 1).	The DAS assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis VAS. The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP = 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 (GH) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP ≤3.2 implied low disease activity.
Percentage of Participants With Low Disease Activity State (LDAS) (≤3.2) - by the End of Course 2	Week 1, 6, 13, and 25 (Course 1 and Course 2).	The DAS assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis VAS. The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP = 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 (GH) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP ≤3.2 implied low disease activity.
Percentage of Participants With Low Disease Activity State (LDAS) (≤3.2) - by the End of Course 3	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).	The DAS assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis VAS. The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP = 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 (GH) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP ≤3.2 implied low disease activity.
Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response - by the End of Course 2	Week 1, 6, 13, and 25 (Course 1 and Course 2).	ACR20 response: ≥ 20 percent (%) improvement in tender/painful joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and CRP.
Percentage of Participants With American College of Rheumatology (ACR) 50% Improvement (ACR50) Response - by the End of Course 1	Week 1, 6, 13, and 25 (Course 1).	ACR50 response: ≥50% improvement in tender/painful joint count; ≥50% improvement in swollen joint count; and ≥50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the HAQ); and CRP.
Mean Change From Initial Study Baseline in Disease Activity Score (DAS28)-C-Reactive Protein (CRP) - by the End of Course 2	Baseline B3281001, Week 1, 6, 13, and 25 (Course 1 and Course 2).	The disease activity score (DAS) assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis Visual Analog Scale (VAS). The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP equals (=) 0.56 square root (sqrt) (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 natural log \[ln\] (CRP \[milligrams per liter, mg/L\] +1) + 0.014 (global assessment of health \[GH\]) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity.
Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on DAS28 - by the End of Course 3	Week 1, 6, 13, and 25 (Course 1 and Course 2) and Week 1, 13, and 25 (Course 3).	The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline greater than (\>) 1.2 with present DAS28 less than or equal to (≤) 3.2; moderate responders had a change from baseline \>0.6 and ≤1.2 with present DAS28 ≤3.2 or change from baseline \>0.6 with present DAS28 \>3.2 and ≤5.1 or change from baseline \>1.2 with present DAS28 \>5.1; non-responders had a change from baseline ≤0.6 with present DAS28 ≤5.1 or change from baseline ≤1.2 with present DAS28 \>5.1.
Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response - by the End of Course 1	Week 1, 6, 13, and 25 (Course 1).	ACR20 response: ≥ 20 percent (%) improvement in tender/painful joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and CRP.
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Tender/Painful Joint Count - by the End of Course 1	Screening, Week 1, 6, 13, and 25 (Course 1).	Sixty-eight joints were assessed by a blinded joint assessor to determine the number of joints that were considered tender or painful. For consistency, a single assessor was preferred to perform all evaluations across the study for an individual participant. The response to pressure/motion on each joint was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not be assessed.
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Tender/Painful Joint Count - by the End of Course 2	Screening, Week 1, 6, 13, and 25 (Course 1 and Course 2).	Sixty-eight joints were assessed by a blinded joint assessor to determine the number of joints that were considered tender or painful. For consistency, a single assessor was preferred to perform all evaluations across the study for an individual participant. The response to pressure/motion on each joint was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not be assessed.
Cluster of Differentiation 19 (CD19+) B Cell Count	Weeks 1, 6, 13, and 25 (Course 1 and Course 2), Weeks 1, 13, 25 (Course 3), and Follow up Months 3, 6, and 9.	Blood samples were assayed for CD19+ B-cell counts using laser scanning cytometry.
Circulating Rheumatoid Factor (RF) Concentrations	Week 1 and 25 (Course 1, Course 2, and Course 3).	RF is the auto-antibody directed against IgG. Blood samples were obtained to determine RF levels in serum.
Percentage of Participants With DAS Remission (DAS28-CRP Less Than [<] 2.6) - by the End of Course 2	Week 1, 6, 13, and 25 (Course 1 and Course 2).	The DAS assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis VAS. The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP = 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 (GH) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP \<2.6 implied remission.
Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response - by the End of Course 3	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).	ACR20 response: ≥ 20 percent (%) improvement in tender/painful joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and CRP.
Percentage of Participants With American College of Rheumatology (ACR) 50% Improvement (ACR50) Response - by the End of Course 3	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).	ACR50 response: ≥50% improvement in tender/painful joint count; ≥50% improvement in swollen joint count; and ≥50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the HAQ); and CRP.
Percentage of Participants With American College of Rheumatology (ACR) 70% Improvement (ACR70) Response - by the End of Course 2	Week 1, 6, 13, and 25 (Course 1 and Course 2).	ACR70 response: ≥70% improvement in tender/painful joint count; ≥70% improvement in swollen joint count; and ≥70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the HAQ); and CRP.
Percentage of Participants With American College of Rheumatology (ACR) 70% Improvement (ACR70) Response - by the End of Course 3	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).	ACR70 response: ≥70% improvement in tender/painful joint count; ≥70% improvement in swollen joint count; and ≥70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the HAQ); and CRP.
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Swollen Joint Count - by the End of Course 2	Screening, Week 1, 6, 13, and 25 (Course 1 and Course 2).	Sixty-six joints were assessed by a blinded joint assessor for swelling. For consistency, a single assessor was preferred to perform all evaluations across the study for an individual participant. The response was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not be assessed.
Mean Change From Initial Study Baseline in Disease Activity Score (DAS28)-C-Reactive Protein (CRP) - by the End of Course 1	Baseline B3281001, Week 1, 6, 13, and 25 (Course 1).	The disease activity score (DAS) assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis Visual Analog Scale (VAS). The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP equals (=) 0.56 square root (sqrt) (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 natural log \[ln\] (CRP \[milligrams per liter, mg/L\] +1) + 0.014 (global assessment of health \[GH\]) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity.
Percentage of Participants With DAS Remission (DAS28-CRP Less Than [<] 2.6) - by the End of Course 1	Week 1, 6, 13, and 25 (Course 1).	The DAS assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis VAS. The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP = 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 (GH) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP \<2.6 implied remission.
Percentage of Participants With DAS Remission (DAS28-CRP Less Than [<] 2.6) - by the End of Course 3	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).	The DAS assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis VAS. The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP = 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 (GH) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP \<2.6 implied remission.
Outcome Measure Using HAQ-DI - by the End of Course 2	Week 1, 6, 13, and 25 (Course 1 and Course 2).	HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each question's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Activities requiring assistance (from people or assistive devices) were adjusted to ≥2 to denote more limited functional status. The questionnaire was to be completed by the participant prior to any procedures during the visit, if possible. Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty. Primary outcome reported in the table is mean HAQ-DI score at each time point, and it is on the scale of HAQ-DI score with the range from 0 to 3.
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Patient's Global Assessment of Arthritis - by the End of Course 1	Week 1, 6, 13, and 25 (Course 1).	Participants were asked the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" Their response was recorded using a 100 mm VAS between 0 (very well) and 100 (very poor).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Patient's Global Assessment of Arthritis - by the End of Course 3	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).	Participants were asked the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" Their response was recorded using a 100 mm VAS between 0 (very well) and 100 (very poor).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Physician's Global Assessment of Arthritis - by the End of Course 1	Week 1, 6, 13, and 25 (Course 1).	The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This evaluation was based on the participant's disease signs, functional capacity and physical examination, and was independent of the Patient's Global Assessment of Arthritis. The investigator's response was recorded using a 100 mm VAS by placing a mark on the scale between 0 (very good) and 100 (very poor).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Tender/Painful Joint Count - by the End of Course 3	Screening, Week 1, 6, 13, and 25 (Course 1 and Course 2), and Screening, Week 1, 13, and 25 (Course 3).	Sixty-eight joints were assessed by a blinded joint assessor to determine the number of joints that were considered tender or painful. For consistency, a single assessor was preferred to perform all evaluations across the study for an individual participant. The response to pressure/motion on each joint was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not be assessed.
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Patient's Assessment of Arthritis Pain - by the End of Course 1	Week 1, 6, 13, and 25 (Course 1).	Participants assessed the severity of their arthritis pain using a 100 millimeter (mm) 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.
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Physician's Global Assessment of Arthritis - by the End of Course 2	Week 1, 6, 13, and 25 (Course 1 and Course 2).	The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This evaluation was based on the participant's disease signs, functional capacity and physical examination, and was independent of the Patient's Global Assessment of Arthritis. The investigator's response was recorded using a 100 mm VAS by placing a mark on the scale between 0 (very good) and 100 (very poor).
Outcome Measure Using HAQ-DI - by the End of Course 1	Week 1, 6, 13, and 25 (Course 1).	HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each question's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Activities requiring assistance (from people or assistive devices) were adjusted to ≥2 to denote more limited functional status. The questionnaire was to be completed by the participant prior to any procedures during the visit, if possible. Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty. Primary outcome reported in the table is mean HAQ-DI score at each time point, and it is on the scale of HAQ-DI score with the range from 0 to 3.
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Patient's Global Assessment of Arthritis - by the End of Course 2	Week 1, 6, 13, and 25 (Course 1 and Course 2).	Participants were asked the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" Their response was recorded using a 100 mm VAS between 0 (very well) and 100 (very poor).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Swollen Joint Count - by the End of Course 3	Screening, Week 1, 6, 13, and 25 (Course 1 and Course 2), and Screening, Week 1, 13, and 25 (Course 3).	Sixty-six joints were assessed by a blinded joint assessor for swelling. For consistency, a single assessor was preferred to perform all evaluations across the study for an individual participant. The response was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not be assessed.
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Patient's Assessment of Arthritis Pain - by the End of Course 2	Week 1, 6, 13, and 25 (Course 1 and Course 2).	Participants assessed the severity of their arthritis pain using a 100 millimeter (mm) 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.
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Physician's Global Assessment of Arthritis - by the End of Course 3	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).	The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This evaluation was based on the participant's disease signs, functional capacity and physical examination, and was independent of the Patient's Global Assessment of Arthritis. The investigator's response was recorded using a 100 mm VAS by placing a mark on the scale between 0 (very good) and 100 (very poor).
Outcome Measure Using HAQ-DI - by the End of Course 3	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).	HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each question's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Activities requiring assistance (from people or assistive devices) were adjusted to ≥2 to denote more limited functional status. The questionnaire was to be completed by the participant prior to any procedures during the visit, if possible. Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty. Primary outcome reported in the table is mean HAQ-DI score at each time point, and it is on the scale of HAQ-DI score with the range from 0 to 3.
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Patient's Assessment of Arthritis Pain - by the End of Course 3	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).	Participants assessed the severity of their arthritis pain using a 100 millimeter (mm) 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.
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Health Assessment Questionnaire - Disability Index (HAQ-DI) - by the End of Course 1	Week 1, 6, 13, and 25 (Course 1).	HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each question's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Activities requiring assistance (from people or assistive devices) were adjusted to ≥2 to denote more limited functional status. The questionnaire was to be completed by the participant prior to any procedures during the visit, if possible. Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty. Primary outcomes reported post baseline mean percent (%) changes in HAQ-DI score. Post baseline values are reported on the % change from initial study Baseline scale.
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Health Assessment Questionnaire - Disability Index (HAQ-DI) - by the End of Course 2	Week 1, 6, 13, and 25 (Course 1 and Course 2).	HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each question's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Activities requiring assistance (from people or assistive devices) were adjusted to ≥2 to denote more limited functional status. The questionnaire was to be completed by the participant prior to any procedures during the visit, if possible. Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty. Primary outcomes reported post baseline mean percent (%) changes in HAQ-DI score. Post baseline values are reported on the % change from initial study Baseline scale.
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Health Assessment Questionnaire - Disability Index (HAQ-DI) - by the End of Course 3	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).	HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each question's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Activities requiring assistance (from people or assistive devices) were adjusted to ≥2 to denote more limited functional status. The questionnaire was to be completed by the participant prior to any procedures during the visit, if possible. Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty. Primary outcomes reported post baseline mean percent (%) changes in HAQ-DI score. Post baseline values are reported on the % change from initial study Baseline scale.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (71): Clínica Medellín S.A. Sede Centro
🇨🇴
Medellín, Antioquia, Colombia
Clinica de La Costa Ltda.
🇨🇴
Barranquilla, Atlantico, Colombia
IPS Centro Integral De Reumatologia del Caribe, CIRCARIBE S.A.S
🇨🇴
Barranquilla, Atlantico, Colombia
CLIDITER, S.A de C.V.
🇲🇽
Mexico City, Distrito Federal, Mexico
Hospital Angeles Clinica Londres
🇲🇽
Mexico City, Distrito Federal, Mexico
C.T. Scanner de Mexico, S.A. de C.V. (CT ONLY)
🇲🇽
Mexico City, Distrito Federal, Mexico
Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi, S.C.
🇲🇽
San Luis Potosi, Mexico
AVA-PETER Ltd.
🇷🇺
St Petersburg, Russian Federation
"AVA-PETER" Ltd - Affiliate Address
🇷🇺
St. Petersburg, Russian Federation
Laboratory of LLC AVA-PETER
🇷🇺
St. Petersburg, Russian Federation
St. Petersburg State Healthcare Institution "Clinical Rheumatology Hospital 25"
🇷🇺
St. Petersburg, Russian Federation
Hospital Bernardette (Emergencies)
🇲🇽
Guadalajara, Jalisco, Mexico
LLC Scientific and Research Medical Complex "Your Health"
🇷🇺
Kazan, Republic OF Tatarstan, Russian Federation
LLC Consulting and Diagnostic Rheumatological Center "Healthy Joints"
🇷🇺
Novosibirsk, Russian Federation
State Institution of Healthcare "Samara Regional Clinical Hospital named after V.D. Seredavin"
🇷🇺
Samara, Russian Federation
Justus J. Fiechtner, MD, PC
🇺🇸
Lansing, Michigan, United States
Clinical Pharmacology Study Group
🇺🇸
Worcester, Massachusetts, United States
Desert Medical Advances
🇺🇸
Palm Desert, California, United States
Arthrocare, Arthritiscare & Research, PC
🇺🇸
Gilbert, Arizona, United States
North Shore-LIJ Health System - Division of Rheumatology and Allergy-Clinical
🇺🇸
Great Neck, New York, United States
IPS Rodrigo Botero S.A.S.
🇨🇴
Medellin, Antioquia, Colombia
QPS Labs
🇺🇸
Newark, Delaware, United States
Bronson Internal Medicine and Rheumatology
🇺🇸
Battle Creek, Michigan, United States
The Chaim Sheba Medical Center
🇮🇱
Tel Hashomer, Israel
UCLA Clinical & Translational Research Center
🇺🇸
Los Angeles, California, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Rheumatology Associates of North Alabama, PC
🇺🇸
Huntsville, Alabama, United States
Centre de Recherche Saint-Louis
🇨🇦
Quebec, Canada
CHI St. Vincent Medical Group Hot Springs
🇺🇸
Hot Springs, Arkansas, United States
New England Research Associates, LLC
🇺🇸
Trumbull, Connecticut, United States
PMG Research of Hickory LLC
🇺🇸
Hickory, North Carolina, United States
West Tennessee Research Institute
🇺🇸
Jackson, Tennessee, United States
Clinique Medicale du Phare (ECG Only)
🇨🇦
Rimouski, Quebec, Canada
UCLA David Geffen School of Medicine
🇺🇸
Los Angeles, California, United States
PMG Research of Hickory, LLC
🇺🇸
Hickory, North Carolina, United States
Rheumatology Research Unit
🇦🇺
Maroochydore, Queensland, Australia
Dartmouth - Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
Southwest Rheumatology Research, LLC
🇺🇸
Mesquite, Texas, United States
Centre de Rhumatologie de l'Est du Quebec
🇨🇦
Rimouski, Quebec, Canada
Private Office
🇲🇽
Guadalajara, Jalisco, Mexico
Dr. Jan Fourie Medical Centre
🇿🇦
KwaZulu Natal, South Africa
Metroplex Clinical Research Center
🇺🇸
Dallas, Texas, United States
Arthritis Clinic
🇺🇸
Jackson, Tennessee, United States
Schlosspark-Klinik GmbH, Internal Medicine II
🇩🇪
Berlin, Germany
Rodrigo Botero S.A.S.
🇨🇴
Medellin, Antioquia, Colombia
Arthritis Associates, PLLC
🇺🇸
Hixson, Tennessee, United States
Mix Supplier S.A.
🇨🇴
Medellín, Antioquia, Colombia
Centro de Reumatologia y Ortopedia
🇨🇴
Barranquilla, Atlantico, Colombia
Organizacion Clinica General Del Norte S.A.
🇨🇴
Barranquilla, Atlantico, Colombia
Hospital Angeles, Centro Medico del Potosi
🇲🇽
San Luis Potosi, Mexico
State Institution of Healthcare "Regional Clinical Hospital for Wars' Veterans"
🇷🇺
Kemerovo, Russian Federation
Local Ethics Committee of LLC AVA-PETER
🇷🇺
St Petersburg, Russian Federation
Division of Rheumatic & Musculoskeletal Diseases
🇬🇧
Leeds, United Kingdom
Panorama Medical Centre - Room 136
🇿🇦
Cape Town, South Africa
Illnois Bone & Joint Institute
🇺🇸
Morton Grove, Illinois, United States
Klein & Associates, M.D., P.A.
🇺🇸
Cumberland, Maryland, United States
Altoona Center for Clinical Research
🇺🇸
Duncansville, Pennsylvania, United States
The Arthritis Group
🇺🇸
Philadelphia, Pennsylvania, United States
Clinical Research Center of Reading, LLC
🇺🇸
Wyomissing, Pennsylvania, United States
Pharmacie Matte et Petit
🇨🇦
Quebec, Canada
Congregación de las Hermanas Franciscanas Misioneras de María Auxiliadora-Clinica La Asuncion
🇨🇴
Barranquilla, Atlantico, Colombia
IPS Centro Integral de Reumatologia del Caribe, CIRCARIBE S.A.S.
🇨🇴
Barranquilla, Atlantico, Colombia
State Budget Institution of Healthcare "Samara Regional Clinical Hospital named after V.D. Seredavin
🇷🇺
Samara, Russian Federation
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
University of Nevada School of Medicine
🇺🇸
Las Vegas, Nevada, United States
Health Research of Oklahoma
🇺🇸
Oklahoma City, Oklahoma, United States
Apocell, Inc
🇺🇸
Houston, Texas, United States
University of South Florida - College of Medicine Carol and Frank Morsani Center
🇺🇸
Tampa, Florida, United States
Covance Central Laboratory Services
🇺🇸
Indianapolis, Indiana, United States
Cincinnati Rheumatic Disease Study Group
🇺🇸
Cincinnati, Ohio, United States
Bluegrass Community Research, Inc.
🇺🇸
Lexington, Kentucky, United States