A Phase 3 interventional study of Placebo and Placebo in Arthritis, Rheumatoid, sponsored by Janssen Research & Development, LLC. Completed at 160 sites in 18 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-01-11.
Sponsored by Janssen Research & Development, LLC · Phase 3, Interventional, and Treatment
The purpose of this study is to assess the efficacy of sirukumab as measured by the reduction of the signs and symptoms of rheumatoid arthritis (RA) and inhibition of radiographic progression in patients with active RA who are unresponsive to treatment with disease-modifying antirheumatic drugs (DMARD).
Patients will be randomly assigned to treatment groups, and they and study personnel will not know the identity of the treatments given. Some patients will receive a placebo, which resembles a medication, but does not contain an active substance. This helps to determine if the study agent is effective. Patients will receive placebo or sirukumab by injection under the skin. The expected duration of the study is 120 weeks, which includes 104 weeks of treatment. Participants who complete participation in the study will be eligible for inclusion into the long-term safety and efficacy study, if enrollment at a participating site is available to them. If they do not participate in the long-term study, they will continue into the safety follow-up for approximately 16 weeks. The placebo-controlled portion of the study is through Week 52, when placebo patients will cross over to one of two sirukumab dose regimens. Patient safety will be monitored throughout the study.
3,554 studies on the registry are indexed under Arthritis; 317 are open to participants now.
This study's enrollment of 1,670 is above the median of 90 across 2,377 interventional studies indexed under Arthritis.
Browse Arthritis studies →Janssen Research & Development, LLC is the lead sponsor of 912 studies on the registry; 76 are open to participants now.
Of its 278 completed or terminated interventional studies of FDA-regulated products, 131 (47%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Drug: Placebo · Drug: Sirukumab
Drug: Sirukumab
Drug: Placebo · Drug: Sirukumab
Form=solution for injection, route=subcutaneous use; every 2 weeks from Week 0 through Week 50.
Form=solution for injection, route=subcutaneous use; Weeks 2, 6, and every 4 weeks through Week 104.
Type=exact, unit=mg, number=50 or 100, form=solution for injection, route=subcutaneous use; every 2 weeks for 100 mg and every 4 weeks for 50 mg, Week 52 through Week 104.
Type=exact, unit=mg, number=100, form=solution for injection, route=subcutaneous use; Weeks 0, 2, and every 2 weeks through Week 104.
Type=exact, unit=mg, number=50, form=solution for injection, route=subcutaneous use; Weeks 0, 4, and every 4 weeks through Week 104.
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Week 16
ACR 20 response is greater than or equal to (\>=) 20 percent (%) improvement in both tender joint count (68) and swollen joint count (66) and \>= 20% improvement in 3 of following 5 assessments:Participant's assessment of pain using visual analog scale (VAS) (0-10 scale, 0=no pain and 10=worst possible pain),Participant's global assessment of disease activity by using VAS (scale ranges from 0 to 10, \[0 = very well to 10 = very poor\]), Physician's global assessment of disease activity using VAS (scale ranges from 0 to 10, \[0=no arthritis activity to 10=extremely active arthritis\]), Participant's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) (scale ranges from 0= no difficulty to 3= inability to perform a task in that area), and Serum C-reactive protein (CRP). Participants were analyzed according to randomized treatment groups they were assigned, regardless of treatments they actually received. Here, TF= treatment failure.
Time frame: Week 16
Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Score at Week 52
The van der Heijde-modified Sharpe (vdH-S) score is defined as a measurement of progression in structural damage. It is the sum of joint erosion (32 joints of the hands and 12 joints of the feet) score and joint space narrowing (JSN) (30 joints of the hands and 12 joints of the feet) score. The joint erosion assessment is scored according to the surface area involved, from 0 to 5, with 0 indicating no erosion and 5 indicating complete collapse of bone whereas the JSN assessment including subluxation, is scored from 0 (normal) to 4 (bony ankylosis or complete luxation). The total score ranges from 0 (best) to 448 (worst) with higher scores indicating more joint damage. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received. Here, EE= early escape.
Time frame: Baseline, Week 52
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24
The Health Assessment Questionnaire-Disability Index (HAQ-DI) score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Baseline, Week 24
Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24
An American College of Rheumatology (ACR) 50 response is defined as \>= 50 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and \>= 50% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, \[0 = very well to 10 = very poor\]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, \[0=no arthritis activity to 10=extremely active arthritis\]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area), and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Week 24
Percentage of Participants With Disease Activity Index Score 28 (DAS28) (C-reactive Protein (CRP) Remission at Week 24
The DAS28 based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. The Disease Activity Index Score 28 (DAS28) C-reactive protein (CRP) remission is defined as a DAS28 (CRP) value of less than 2.6 at a visit. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Week 24
Percentage of Participants With Major Clinical Response (MCR) at Week 52
MCR- participant achieving ACR 70 response for 6 continuous months (24 weeks) in the study period (i.e., through Week 52). An ACR 70 response is defined as \>= 70% improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and \>= 70% improvement in 3 of the following 5 assessments Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (scale ranges from 0 to 10, \[0 = very well to 10 = very poor\]), Physician's global assessment of disease activity using VAS (scale ranges from 0 to 10, \[0=no arthritis to 10=extremely active arthritis\]), Participant's assessment of physical function as measured by HAQ-DI (scale ranges from 0= no difficulty, to 3= inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Week 52
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response Through Week 52
An ACR 20 response is defined as \>= 20 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and \>= 20% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, \[0 = very well to 10 = very poor\]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, \[0=no arthritis activity to 10=extremely active arthritis\]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area), and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Week 2, 4, 6, 8, 12, 18, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Percentage of Participants With an American College of Rheumatology (ACR) 50 Response
An ACR 50 response is defined as \>= 50 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and \>= 50% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, \[0 = very well to 10 = very poor\]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, \[0=no arthritis activity to 10=extremely active arthritis\]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 28, 32, 36, 40, 44, 48 and 52
Percentage of Participants With an American College of Rheumatology (ACR) 70 Response Through Week 52
An ACR 70 response is defined as \>= 70 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and \>= 70% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, \[0 = very well to 10 = very poor\]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, \[0=no arthritis activity to 10=extremely active arthritis\]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Percentage of Participants With an American College of Rheumatology (ACR) 90 Response Through Week 52
An ACR 90 response is defined as \>= 90 percent (%) improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and \>= 90% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, \[0 = very well to 10 = very poor\]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, \[0=no arthritis activity to 10=extremely active arthritis\]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Percentage of Participants With Disease Activity Index Score 28 (DAS28) C-reactive Protein (CRP) Response Through Week 52
DAS28 based on C-Reactive Protein (CRP), a statistically derived index combining tender joints (28), swollen joints (28), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both upper right extremity and upper left extremity as well as knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. Good responders: improvement from baseline greater than (\>) 1.2 with DAS28 less than or equal to (\<=) 3.2; moderate responders: improvement from baseline \>1.2 with DAS28 \>3.2 to \<=5.1 or improvement from baseline \>0.6 to \<=1.2 with DAS28 \<=5.1; non-responders: improvement from baseline \<=0.6 or improvement from baseline \>0.6 and \<=1.2 with DAS28 \>5.1. Participants were analyzed according to randomized treatment groups they were assigned to, regardless of treatments they actually received.
Time frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Change From Baseline in Disease Activity Index Score 28 (DAS28) C-reactive Protein (CRP) Through Week 52
The DAS28 based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. A negative change from baseline in DAS28 (CRP) (that is, a decrease from baseline) indicates improvement from baseline. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Percentage of Participants With Disease Activity Index Score 28 (DAS28) (C-reactive Protein (CRP) Remission Through Week 52
The DAS28 based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. The Disease Activity Index Score 28 (DAS28) C-reactive protein (CRP) remission is defined as a DAS28 (CRP) value of less than 2.6 at a visit. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 28, 32, 36, 40, 44, 48 and 52
Change From Baseline in Simplified Disease Activity Index (SDAI) Score Through Week 52
The SDAI score is a derived score combining tender joints (28 joints), swollen joints (28 joints), patient's global assessment of disease activity, physician's global assessments of disease activity, and CRP. The total score range is from 0 to 86 with a lower score indicating less disease activity. A negative change from baseline indicates an improvement and a positive change from baseline indicates a worsening. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Change From Baseline in Clinical Disease Activity Index (CDAI) Score Through Week 52
The CDAI score is a derived score of 4 components: tender joints (28 joints), swollen joints (28 joints), patient's global assessment of disease activity, and physician's global assessments of disease activity. The total score ranges from 0 to 76 with a lower score indicating less disease activity. A negative change in CDAI score indicates an improvement in disease activity and a positive change in score indicates a worsening of disease activity. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Percentage of Participants With Simplified Disease Activity Index Based (SDAI-based) American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) Remission Through Week 52
Participant having SDAI-based ACR/EULAR remission at a visit if SDAI score is of \<= 3.3. SDAI derived by combining 5 disease assessments: tender joint (28), swollen joint (28) counts, participants global assessment of disease activity using VAS (scale ranges from 0 to 10 \[0 =very well to 10 = very poor\]), physicians global assessment of disease activity using VAS (scale ranges from 0 to 10 \[0=no arthritis to 10=extremely active arthritis\]) and CRP. 28 joints evaluated for swelling and tenderness are same set of 28 joints used in DAS28 includes shoulder, elbow, wrist, MCP1, MCP2, MCP3, MCP4, MCP5, PIP1, PIP2, PIP3, PIP4, PIP5 joints of upper right and left extremities and knee joints of lower right and left extremities. Change from baseline in SDAI score measures change in disease activity, where negative change= improvement and positive change= worsening. Participants were analyzed according to randomized treatment groups they were assigned regardless of treatments actually received.
Time frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Percentage of Participants With Boolean-based American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) Remission Through Week 52
A participant was considered as having achieved the Boolean-based American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) remission at a visit if all of the following 4 criteria were met at that visit: Tender joint count (68 joints) less than or equal to (\<=) 1; Swollen joint count (66 joints) \<=1; CRP \<=1 milligram per deciliter (mg/dL); Patient's Global Assessment of Disease Activity \<=1 on a 0 (very well) to 10 (very poor) VAS. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Through Week 52
The Health Assessment Questionnaire-Disability Index (HAQ-DI) score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Negative change reflects an improvement and a positive change reflects a worsening. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 28, 32, 36, 40, 44, 48 and 52
Area Under the Curve (AUC) of Change From Baseline in HAQ-DI Score From Week 0 Through Week 24 and From Week 0 Through Week 52
HAQ-DI has 20-question in 8 functional areas: dressing, arising, eating, walking, hygiene, reaching, gripping, and daily living activities, scored from 0=no difficulty to 3=inability to perform task in that area. Overall score computed as sum of domain score divided by number of domains answered. Total possible score range 0= least difficulty to 3= extreme difficulty. AUC of change from baseline in HAQ-DI score is AUC of change from baseline in HAQ-DI score versus time. AUC was calculated based on measurement (observed HAQ-DI score change from baseline) at scheduled visits using trapezoidal rule.Functional status was determined as cumulative measure of HAQ-DI over 1 year by using AUC of change from baseline in HAQ-DI score through week 52. Decreases in AUC of change from baseline in HAQ-DI means greater average improvement in physical function over time. Participants analyzed according to randomized treatment groups they were assigned, regardless of treatments they actually received.
Time frame: Week 0 Through Week 24 and 52
Percentage of Participants With Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Through Week 52
HAQ-DI response was defined as change of less than -0.22 from baseline in HAQ-DI score. The HAQ-DI score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Percentage of Participants With Health Assessment Questionnaire-Disability Index (HAQ-DI) Score of Less Than or Equal to 0.5
HAQ-DI score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Score at Week 24
vdH-S score is defined as a measurement of progression in structural damage. It is the sum of joint erosion (32 joints of the hands and 12 joints of the feet) score and joint space narrowing (JSN) (30 joints of the hands and 12 joints of the feet) score. The joint erosion assessment is scored according to the surface area involved, from 0 to 5, with 0 indicating no erosion and 5 indicating complete collapse of bone whereas the JSN assessment including subluxation, is scored from 0 (normal) to 4 (bony ankylosis or complete luxation). The total score ranges from 0 (best) to 448 (worst) with higher scores indicating more joint damage. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Baseline, Week 24
Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Sub-score by Type of Damage (Erosion or JSN) at Week 24 and 52
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32\*5) and MAX JES for F- 120 (12\*10 \[5\*2 sides of foot\]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30\*4), and MAX JSS for F-48(12\*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS (i.e., JE score + JSN score) of 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Baseline, Week 24 and 52
Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Sub-score by Region Hand or Feet and Type Erosion or JSN at Week 24 and 52
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32\*5) and MAX JES for F- 120 (12\*10 \[5\*2 sides of foot\]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30\*4), and MAX JSS for F-48(12\*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS (i.e., erosion score + JSN score) of 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Baseline, Week 24 and 52
Percentage of Participants With Change From Baseline in Van Der Heijde Modified Sharpe Score (vdH-S Score) Greater Than Smallest Detectable Change (SDC) at Weeks 24 and 52
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S). JE is summary of erosion severity in 32 of hand and 12 of feet joints, scored according to the surface area, from 0 (no erosion) to 5 (complete collapse of bone) whereas the JSN is summary of severity of 30 of hand and 12 of feet joints, scored according to the subluxation from 0 (normal) to 4 (bony ankylosis or complete luxation). The SDC is smallest change in score that is considered to be assessed correctly based on limits of agreement (that is., above the measurement error). The SDC for change from baseline in vdH-S Score is determined as: SDC=1.96 \* SD / (root 2 \* root k), where SD is the standard deviation of the difference between 2 readers in change from baseline in vdH-S score; k is the number of readers. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Weeks 24 and 52
Percentage of Participants With a Change of Less Than or Equal to 0 From Baseline in Van Der Heijde Modified Sharpe (vdH-S) Score at Weeks 24 and 52
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32\*5) and MAX JES for F- 120 (12\*10 \[5\*2 sides of foot\]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30\*4), and MAX JSS for F-48(12\*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS of (i.e., erosion score + JSN score) 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Week 24 and 52
Change From Baseline in Van Der Heijde Modified Sharpe Score (vdH-S Score) by Reader at Weeks 24 and 52
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32\*5) and MAX JES for F- 120 (12\*10 \[5\*2 sides of foot\]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30\*4), and MAX JSS for F-48(12\*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS (i.e., JE score + JSN score) of 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Baseline, Weeks 24 and 52
Change From Baseline in Serum C-reactive Protein (CRP) Levels Through Week 52
Serum CRP is a marker of systemic inflammation. A negative change from baseline in CRP represents improvement. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Change From Baseline in the Duration of Morning Stiffness Through Week 52
Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness in minutes (If none was present = 0; If morning stiffness was continuing at the time of assessment or was unusual compared to the recent past, average of duration of stiffness over the past 3 days was reported; If stiffness persisted the entire day, 1440 minutes was recorded). Negative values for this outcome measure represent improvement, i.e. shortening of duration of morning stiffness. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Change From Baseline in Physical and Mental Component Summary Scores of 36-Item Short Form Health Survey (SF-36) at Weeks 24 and 52
SF-36 questionnaire is health related quality of life (QOL) instrument with 36 questions with 8 multi-item scales (evaluated limitations in): physical functioning due to health problems; usual role activities due to physical health problems; Bodily pain; General mental health (psychological distress and well-being); usual role activities due to personal or emotional problems; social functioning due to physical or mental health problems; Vitality (energy and fatigue); General health perception. Each 8 scales scored from 0 to 100 with higher scores= better health. Based on scale scores, summary scores, physical component score (PCS) and mental component score (MCS) will be derived. Scoring is derived based on algorithm developed in software provided by developer. Summary MCS and PCS score is also scaled from 0 to 100 with higher scores= better health. Participants were analyzed according to randomized treatment groups they were assigned regardless of treatments they actually received.
Time frame: Baseline, Week 24 and 52
Percentage of Participants With Greater Than or Equal to 4-Point Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 8, 16, 24, 36 and 52
The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) is a questionnaire that assesses self-reported tiredness, weakness, and difficulty conducting usual activities due to fatigue. The questionnaire consists of 13 questions that assess a participant's level of fatigue and tiredness over the last 7 days. Each question is graded on a 5-point scale (0 - 4); and accordingly, the total FACIT-Fatigue scores can range from 0 to 52, with lower score reflecting more fatigue and higher scores reflecting less fatigue. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Week 8, 16, 24, 36 and 52
Change From Baseline in Total Scores of Work Limitations Questionnaire (WLQ) Week 8, 16, 24, 36 and 52
The Work Limitations Questionnaire (WLQ) was used to measure the impairment in work-related productivity, with reference to the previous two weeks. Each work-related question is scored from 0 to 4 and the total score ranges from 0-100, with lower scores signifying fewer limitations at work. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Baseline, Week 8, 16, 24, 36 and 52
Change From Baseline in EuroQol Health State Visual Analogue Scale (EQ VAS)
The EuroQol Health State Visual Analogue Scale (EQ VAS) records the respondent's self-rated health on a vertical line, VAS where the endpoints are labeled as 0= 'Worst imaginable health state' and 100= 'Best imaginable health state'. The EQ VAS can be used as a quantitative measure of health outcome as judged by the individual respondents. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: Baseline, Week 8, 16, 24, 36 and 52
Change From Baseline in EuroQol EQ-5D-3L Descriptive System
The EQ-5D-3L Descriptive System comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 indicating "full health" and 0 representing dead. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
Time frame: at Week 8, 16, 24, and 52
| Milestone | Placebo | Placebo to 50 mg q4w Due to EE/LE/CO | Sirukumab 50 mg q4w | Placebo to 100 mg q2w Due to EE/LE/CO | Sirukumab 100 mg q2w |
|---|---|---|---|---|---|
| Started | 556 | 0 | 557 | 0 | 557 |
| Participants re-randomized at week 18 | 187 | 0 | 0 | 0 | 0 |
| Participants re-randomized at week 40 | 24 | 0 | 0 | 0 | 0 |
| Completed | 458 | 0 | 481 | 0 | 470 |
| Not completed | 98 | 0 | 76 | 0 | 87 |
| Withdrew: Lost to follow-up | 5 | 0 | 4 | 0 | 3 |
| Withdrew: Withdrawal by subject | 19 | 0 | 12 | 0 | 16 |
| Withdrew: Adverse event | 25 | 0 | 41 | 0 | 42 |
| Withdrew: Death | 5 | 0 | 2 | 0 | 4 |
| Withdrew: Lack of efficacy | 24 | 0 | 5 | 0 | 14 |
| Withdrew: Physician decision | 4 | 0 | 1 | 0 | 2 |
| Withdrew: Pregnancy | 1 | 0 | 1 | 0 | 0 |
| Withdrew: Other | 15 | 0 | 10 | 0 | 6 |
| Milestone | Placebo | Placebo to 50 mg q4w Due to EE/LE/CO | Sirukumab 50 mg q4w | Placebo to 100 mg q2w Due to EE/LE/CO | Sirukumab 100 mg q2w |
|---|---|---|---|---|---|
| Started | 0 | 243 | 481 | 241 | 470 |
| Treated | 0 | 242 | 481 | 241 | 470 |
| Completed | 0 | 200 | 414 | 195 | 429 |
| Not completed | 0 | 43 | 67 | 46 | 41 |
| Withdrew: Lost to follow-up | 0 | 2 | 4 | 2 | 1 |
| Withdrew: Withdrawal by subject | 0 | 7 | 12 | 8 | 4 |
| Withdrew: Adverse event | 0 | 12 | 26 | 21 | 27 |
| Withdrew: Death | 0 | 4 | 2 | 5 | 0 |
| Withdrew: Lack of efficacy | 0 | 6 | 11 | 2 | 3 |
| Withdrew: Physician decision | 0 | 1 | 0 | 0 | 2 |
| Withdrew: Pregnancy | 0 | 0 | 1 | 2 | 1 |
| Withdrew: Other | 0 | 11 | 11 | 6 | 3 |
| Milestone | Placebo | Placebo to 50 mg q4w Due to EE/LE/CO | Sirukumab 50 mg q4w | Placebo to 100 mg q2w Due to EE/LE/CO | Sirukumab 100 mg q2w |
|---|---|---|---|---|---|
| Started | 109 | 27 | 105 | 36 | 114 |
| Safety population | 109 | 26 | 105 | 36 | 114 |
| Completed | 79 | 20 | 72 | 26 | 85 |
| Not completed | 30 | 7 | 33 | 10 | 29 |
| Withdrew: Lost to follow-up | 3 | 1 | 2 | 1 | 1 |
| Withdrew: Withdrawal by subject | 12 | 4 | 11 | 3 | 14 |
| Withdrew: Other | 15 | 2 | 20 | 6 | 14 |
ACR 20 response is greater than or equal to (\>=) 20 percent (%) improvement in both tender joint count (68) and swollen joint count (66) and \>= 20% improvement in 3 of following 5 assessments:Participant's assessment of pain using visual analog scale (VAS) (0-10 scale, 0=no pain and 10=worst possible pain),Participant's global assessment of disease activity by using VAS (scale ranges from 0 to 10, \[0 = very well to 10 = very poor\]), Physician's global assessment of disease activity using VAS (scale ranges from 0 to 10, \[0=no arthritis activity to 10=extremely active arthritis\]), Participant's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) (scale ranges from 0= no difficulty to 3= inability to perform a task in that area), and Serum C-reactive protein (CRP). Participants were analyzed according to randomized treatment groups they were assigned, regardless of treatments they actually received. Here, TF= treatment failure.
| Percentage of Participants | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Week 16 | 26.4 | 54.8 | 53.5 |
The van der Heijde-modified Sharpe (vdH-S) score is defined as a measurement of progression in structural damage. It is the sum of joint erosion (32 joints of the hands and 12 joints of the feet) score and joint space narrowing (JSN) (30 joints of the hands and 12 joints of the feet) score. The joint erosion assessment is scored according to the surface area involved, from 0 to 5, with 0 indicating no erosion and 5 indicating complete collapse of bone whereas the JSN assessment including subluxation, is scored from 0 (normal) to 4 (bony ankylosis or complete luxation). The total score ranges from 0 (best) to 448 (worst) with higher scores indicating more joint damage. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received. Here, EE= early escape.
| Units on a Scale | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Score at Week 52 | 3.69 ± 9.245 | 0.50 ± 2.961 | 0.46 ± 3.258 |
The Health Assessment Questionnaire-Disability Index (HAQ-DI) score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Units on Scale | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 | -0.2179 ± 0.53081 | -0.4262 ± 0.57631 | -0.4610 ± 0.56784 |
An American College of Rheumatology (ACR) 50 response is defined as \>= 50 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and \>= 50% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, \[0 = very well to 10 = very poor\]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, \[0=no arthritis activity to 10=extremely active arthritis\]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area), and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Percentage of Participants | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24 | 12.4 | 30.2 | 33.2 |
The DAS28 based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. The Disease Activity Index Score 28 (DAS28) C-reactive protein (CRP) remission is defined as a DAS28 (CRP) value of less than 2.6 at a visit. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Percentage of Participants | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Percentage of Participants With Disease Activity Index Score 28 (DAS28) (C-reactive Protein (CRP) Remission at Week 24 | 5.6 | 26.0 | 25.5 |
MCR- participant achieving ACR 70 response for 6 continuous months (24 weeks) in the study period (i.e., through Week 52). An ACR 70 response is defined as \>= 70% improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and \>= 70% improvement in 3 of the following 5 assessments Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (scale ranges from 0 to 10, \[0 = very well to 10 = very poor\]), Physician's global assessment of disease activity using VAS (scale ranges from 0 to 10, \[0=no arthritis to 10=extremely active arthritis\]), Participant's assessment of physical function as measured by HAQ-DI (scale ranges from 0= no difficulty, to 3= inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Percentage of Participants | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Percentage of Participants With Major Clinical Response (MCR) at Week 52 | 1.8 | 5.4 | 9.0 |
An ACR 20 response is defined as \>= 20 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and \>= 20% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, \[0 = very well to 10 = very poor\]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, \[0=no arthritis activity to 10=extremely active arthritis\]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area), and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Percentage of Participants | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Week 2 | 7.4 | 18.3 | 15.4 |
| Week 4 | 14.2 | 36.3 | 33.8 |
| Week 6 | 20.3 | 45.8 | 46.9 |
| Week 8 | 25.9 | 47.2 | 51.3 |
| Week 12 | 27.3 | 53.1 | 53.3 |
| Week 18 | 29.3 | 54.4 | 56.9 |
| Week 20 | 29.5 | 53.7 | 52.8 |
| Week 24 | 27.0 | 53.7 | 56.0 |
| Week 28 | 31.5 | 53.1 | 57.3 |
| Week 32 | 29.5 | 53.3 | 56.7 |
| Week 36 | 28.4 | 54.0 | 58.2 |
| Week 40 | 28.8 | 53.3 | 53.3 |
| Week 44 | 27.7 | 49.2 | 54.0 |
| Week 48 | 26.8 | 50.1 | 54.8 |
| Week 52 | 26.6 | 49.9 | 54.8 |
An ACR 50 response is defined as \>= 50 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and \>= 50% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, \[0 = very well to 10 = very poor\]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, \[0=no arthritis activity to 10=extremely active arthritis\]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Percentage of Participants | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Week 2 | 1.1 | 3.2 | 2.0 |
| Week 4 | 2.5 | 9.2 | 9.9 |
| Week 6 | 4.1 | 15.6 | 14.0 |
| Week 8 | 7.7 | 20.3 | 18.9 |
| Week 12 | 10.1 | 24.6 | 28.0 |
| Week 16 | 10.8 | 30.0 | 26.2 |
| Week 18 | 11.7 | 31.2 | 31.2 |
| Week 20 | 13.5 | 32.7 | 33.4 |
| Week 28 | 15.1 | 31.6 | 33.0 |
| Week 32 | 14.0 | 33.6 | 35.0 |
| Week 36 | 12.2 | 33.4 | 34.5 |
| Week 40 | 13.3 | 31.1 | 33.4 |
| Week 44 | 14.2 | 31.4 | 33.9 |
| Week 48 | 14.4 | 32.9 | 34.8 |
| Week 52 | 13.8 | 30.3 | 35.5 |
An ACR 70 response is defined as \>= 70 % improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and \>= 70% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, \[0 = very well to 10 = very poor\]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, \[0=no arthritis activity to 10=extremely active arthritis\]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Percentage of Participants | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Week 2 | 0.4 | 0.7 | 0.4 |
| Week 4 | 0.5 | 2.0 | 3.1 |
| Week 6 | 1.6 | 4.7 | 4.5 |
| Week 8 | 1.6 | 7.2 | 7.2 |
| Week 12 | 3.1 | 10.4 | 10.6 |
| Week 16 | 4.0 | 13.5 | 13.5 |
| Week 18 | 4.3 | 12.6 | 14.7 |
| Week 20 | 4.0 | 13.1 | 16.0 |
| Week 24 | 3.4 | 14.9 | 16.3 |
| Week 28 | 5.2 | 16.0 | 16.5 |
| Week 32 | 4.7 | 17.4 | 17.2 |
| Week 36 | 4.7 | 15.8 | 16.2 |
| Week 40 | 5.0 | 16.9 | 17.6 |
| Week 44 | 5.2 | 16.3 | 17.1 |
| Week 48 | 6.8 | 18.5 | 17.8 |
| Week 52 | 5.4 | 16.5 | 18.5 |
An ACR 90 response is defined as \>= 90 percent (%) improvement in both tender joint count (68 joints) and swollen joint count (66 joints) and \>= 90% improvement in 3 of the following 5 assessments: Participant's assessment of pain using VAS (0-10 scale, 0=no pain and 10=worst possible pain), Participant's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, \[0 = very well to 10 = very poor\]), Physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, \[0=no arthritis activity to 10=extremely active arthritis\]), Participant's assessment of physical function as measured by HAQ-DI (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and Serum CRP. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Percentage of Participants | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Week 2 | 0 | 0 | 0 |
| Week 4 | 0 | 0.2 | 0.2 |
| Week 6 | 0.2 | 0.2 | 0.2 |
| Week 8 | 0.2 | 1.1 | 0.5 |
| Week 12 | 0.5 | 2.2 | 1.8 |
| Week 16 | 0.9 | 2.5 | 2.9 |
| Week 18 | 1.1 | 2.5 | 2.5 |
| Week 20 | 0.5 | 3.6 | 4.1 |
| Week 24 | 0.5 | 3.4 | 5.2 |
| Week 28 | 0.4 | 4.5 | 4.7 |
| Week 32 | 1.1 | 4.1 | 5.7 |
| Week 36 | 0.9 | 4.8 | 5.4 |
| Week 40 | 0.7 | 5.4 | 6.1 |
| Week 44 | 0.5 | 5.0 | 6.6 |
| Week 48 | 0.7 | 4.7 | 6.3 |
| Week 52 | 1.3 | 4.5 | 5.6 |
DAS28 based on C-Reactive Protein (CRP), a statistically derived index combining tender joints (28), swollen joints (28), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both upper right extremity and upper left extremity as well as knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. Good responders: improvement from baseline greater than (\>) 1.2 with DAS28 less than or equal to (\<=) 3.2; moderate responders: improvement from baseline \>1.2 with DAS28 \>3.2 to \<=5.1 or improvement from baseline \>0.6 to \<=1.2 with DAS28 \<=5.1; non-responders: improvement from baseline \<=0.6 or improvement from baseline \>0.6 and \<=1.2 with DAS28 \>5.1. Participants were analyzed according to randomized treatment groups they were assigned to, regardless of treatments they actually received.
| Percentage of Participants | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Week 2 | 18.5 | 72.0 | 72.4 |
| Week 4 | 28.1 | 80.1 | 78.3 |
| Week 6 | 36.7 | 82.4 | 80.3 |
| Week 8 | 38.5 | 81.7 | 81.3 |
| Week 12 | 43.7 | 83.3 | 81.3 |
| Week 16 | 42.6 | 80.4 | 79.5 |
| Week 18 | 41.5 | 79.7 | 79.4 |
| Week 20 | 41.5 | 73.8 | 72.5 |
| Week 24 | 37.9 | 71.5 | 72.2 |
| Week 28 | 41.2 | 69.7 | 72.2 |
| Week 32 | 41.4 | 68.2 | 70.6 |
| Week 36 | 39.7 | 67.7 | 69.8 |
| Week 40 | 39.2 | 66.8 | 67.9 |
| Week 44 | 37.6 | 63.2 | 64.6 |
| Week 48 | 36.7 | 61.9 | 64.6 |
| Week 52 | 35.6 | 62.5 | 64.3 |
The DAS28 based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. A negative change from baseline in DAS28 (CRP) (that is, a decrease from baseline) indicates improvement from baseline. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Units on a Scale | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Change at Week 2 | -0.319 ± 0.7677 | -1.316 ± 0.7776 | -1.284 ± 0.7605 |
| Change at Week 4 | -0.515 ± 0.9287 | -1.638 ± 0.9759 | -1.627 ± 0.9529 |
| Change at Week 6 | -0.707 ± 1.0599 | -1.886 ± 1.0622 | -1.888 ± 1.0340 |
| Change at Week 8 | -0.754 ± 1.1013 | -2.016 ± 1.1183 | -2.031 ± 1.1138 |
| Change at Week 12 | -0.881 ± 1.1727 | -2.187 ± 1.1995 | -2.185 ± 1.1950 |
| Change at Week 16 | -0.908 ± 1.2834 | -2.264 ± 1.2443 | -2.282 ± 1.2283 |
| Change at Week 18 | -0.895 ± 1.2986 | -2.286 ± 1.2690 | -2.335 ± 1.2314 |
| Change at Week 20 | -0.920 ± 1.2973 | -2.367 ± 1.3368 | -2.380 ± 1.3158 |
| Change at Week 24 | -0.912 ± 1.3180 | -2.356 ± 1.3599 | -2.402 ± 1.3048 |
| Change at Week 28 | -0.979 ± 1.3752 | -2.417 ± 1.4068 | -2.440 ± 1.3245 |
| Change at Week 32 | -1.010 ± 1.3904 | -2.451 ± 1.4141 | -2.479 ± 1.3304 |
| Change at Week 36 | -1.019 ± 1.4020 | -2.461 ± 1.3951 | -2.497 ± 1.3231 |
| Change at Week 40 | -0.985 ± 1.4054 | -2.462 ± 1.4180 | -2.459 ± 1.3901 |
| Change at Week 44 | -0.994 ± 1.4117 | -2.442 ± 1.4364 | -2.477 ± 1.4381 |
| Change at Week 48 | -1.026 ± 1.4755 | -2.482 ± 1.4630 | -2.488 ± 1.3783 |
| Change at Week 52 | -0.992 ± 1.4431 | -2.491 ± 1.4305 | -2.476 ± 1.4109 |
The DAS28 based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. The Disease Activity Index Score 28 (DAS28) C-reactive protein (CRP) remission is defined as a DAS28 (CRP) value of less than 2.6 at a visit. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Percentage of Participants | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Week 2 | 0.5 | 2.5 | 2.7 |
| Week 4 | 1.6 | 7.9 | 9.3 |
| Week 6 | 3.1 | 10.2 | 12.6 |
| Week 8 | 3.2 | 13.6 | 17.8 |
| Week 12 | 4.3 | 18.3 | 19.6 |
| Week 16 | 5.8 | 21.2 | 21.9 |
| Week 18 | 6.1 | 22.8 | 23.7 |
| Week 20 | 5.8 | 26.4 | 25.5 |
| Week 28 | 7.7 | 27.5 | 27.1 |
| Week 32 | 7.7 | 29.6 | 28.4 |
| Week 36 | 8.5 | 29.1 | 28.0 |
| Week 40 | 7.2 | 27.8 | 27.3 |
| Week 44 | 8.5 | 28.2 | 27.5 |
| Week 48 | 9.0 | 29.6 | 30.2 |
| Week 52 | 8.8 | 30.0 | 29.1 |
The SDAI score is a derived score combining tender joints (28 joints), swollen joints (28 joints), patient's global assessment of disease activity, physician's global assessments of disease activity, and CRP. The total score range is from 0 to 86 with a lower score indicating less disease activity. A negative change from baseline indicates an improvement and a positive change from baseline indicates a worsening. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Units on a Scale | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Change at Week 2 | -4.5129 ± 9.68032 | -9.1095 ± 9.64598 | -7.9649 ± 9.58765 |
| Change at Week 4 | -7.3134 ± 11.87959 | -13.3976 ± 12.00410 | -12.2156 ± 11.65262 |
| Change at Week 6 | -9.5833 ± 13.15531 | -16.1013 ± 12.80166 | -15.4404 ± 12.18642 |
| Change at Week 8 | -10.0752 ± 13.54599 | -17.6624 ± 12.98109 | -17.1302 ± 12.92830 |
| Change at Week 12 | -11.5975 ± 14.53181 | -19.6639 ± 13.67016 | -19.0635 ± 13.63444 |
| Change at Week 16 | -11.3507 ± 15.72864 | -20.3221 ± 14.14177 | -20.0652 ± 13.85171 |
| Change at Week 18 | -10.6805 ± 16.31549 | -20.1215 ± 14.75683 | -20.4858 ± 13.72370 |
| Change at Week 20 | -11.0425 ± 16.42770 | -20.8300 ± 15.31245 | -20.8508 ± 14.44400 |
| Change at Week 24 | -11.1443 ± 16.37909 | -20.7459 ± 15.48312 | -21.0858 ± 14.57962 |
| Change at Week 28 | -11.7828 ± 17.04652 | -21.3535 ± 15.98762 | -21.5524 ± 14.69362 |
| Change at Week 32 | -12.0835 ± 17.11297 | -21.8176 ± 16.15549 | -21.8530 ± 14.58393 |
| Change at Week 36 | -12.2107 ± 17.24703 | -21.9077 ± 15.95251 | -22.1040 ± 14.54871 |
| Change at Week 40 | -11.9185 ± 17.32206 | -21.7862 ± 16.12260 | -21.6692 ± 15.33635 |
| Change at Week 44 | -11.8730 ± 17.41934 | -21.4843 ± 16.33985 | -21.5514 ± 15.78476 |
| Change at Week 48 | -11.9055 ± 17.91398 | -21.7238 ± 16.45520 | -21.7991 ± 15.34514 |
| Change at Week 52 | -11.7647 ± 17.61074 | -21.9130 ± 16.32611 | -21.7344 ± 15.64620 |
The CDAI score is a derived score of 4 components: tender joints (28 joints), swollen joints (28 joints), patient's global assessment of disease activity, and physician's global assessments of disease activity. The total score ranges from 0 to 76 with a lower score indicating less disease activity. A negative change in CDAI score indicates an improvement in disease activity and a positive change in score indicates a worsening of disease activity. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Units on a Scale | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Change at Week 2 | -4.38 ± 9.210 | -6.82 ± 9.350 | -5.65 ± 9.014 |
| Change at Week 4 | -7.09 ± 11.241 | -11.13 ± 11.699 | -9.88 ± 11.166 |
| Change at Week 6 | -9.24 ± 12.407 | -13.79 ± 12.416 | -13.10 ± 11.599 |
| Change at Week 8 | -9.72 ± 12.714 | -15.37 ± 12.593 | -14.79 ± 12.438 |
| Change at Week 12 | -11.19 ± 13.625 | -17.36 ± 13.223 | -16.74 ± 13.098 |
| Change at Week 16 | -10.86 ± 14.716 | -18.04 ± 13.651 | -17.75 ± 13.261 |
| Change at Week 18 | -10.24 ± 15.245 | -17.82 ± 14.291 | -18.17 ± 13.204 |
| Change at Week 20 | -10.57 ± 15.338 | -18.53 ± 14.809 | -18.57 ± 13.910 |
| Change at Week 24 | -10.68 ± 15.302 | -18.45 ± 14.936 | -18.80 ± 14.075 |
| Change at Week 28 | -11.27 ± 15.926 | -19.06 ± 15.395 | -19.27 ± 14.168 |
| Change at Week 32 | -11.55 ± 15.950 | -19.57 ± 15.549 | -19.56 ± 14.095 |
| Change at Week 36 | -11.70 ± 16.099 | -19.66 ± 15.455 | -19.80 ± 14.084 |
| Change at Week 40 | -11.46 ± 16.236 | -19.54 ± 15.640 | 19.3 ± 14.833 |
| Change at Week 44 | -11.41 ± 16.126 | -19.24 ± 15.888 | -19.26 ± 15.264 |
| Change at Week 48 | -11.47 ± 16.594 | -19.47 ± 15.951 | -19.50 ± 14.871 |
| Change at Week 52 | -11.38 ± 16.348 | -19.67 ± 15.834 | -19.44 ± 15.115 |
Participant having SDAI-based ACR/EULAR remission at a visit if SDAI score is of \<= 3.3. SDAI derived by combining 5 disease assessments: tender joint (28), swollen joint (28) counts, participants global assessment of disease activity using VAS (scale ranges from 0 to 10 \[0 =very well to 10 = very poor\]), physicians global assessment of disease activity using VAS (scale ranges from 0 to 10 \[0=no arthritis to 10=extremely active arthritis\]) and CRP. 28 joints evaluated for swelling and tenderness are same set of 28 joints used in DAS28 includes shoulder, elbow, wrist, MCP1, MCP2, MCP3, MCP4, MCP5, PIP1, PIP2, PIP3, PIP4, PIP5 joints of upper right and left extremities and knee joints of lower right and left extremities. Change from baseline in SDAI score measures change in disease activity, where negative change= improvement and positive change= worsening. Participants were analyzed according to randomized treatment groups they were assigned regardless of treatments actually received.
| Percentage of Participants | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Week 2 | 0.2 | 0 | 0 |
| Week 4 | 0.4 | 0.2 | 1.3 |
| Week 6 | 0.4 | 1.6 | 2.3 |
| Week 8 | 0.7 | 2.9 | 2.9 |
| Week 12 | 1.6 | 4.8 | 5.2 |
| Week 16 | 2.2 | 5.4 | 6.6 |
| Week 18 | 1.6 | 6.3 | 6.8 |
| Week 20 | 1.6 | 7.5 | 7.7 |
| Week 24 | 2.3 | 8.1 | 9.5 |
| Week 28 | 2.3 | 9.0 | 8.4 |
| Week 32 | 2.9 | 9.7 | 10.2 |
| Week 36 | 1.8 | 10.1 | 10.6 |
| Week 40 | 2.5 | 11.5 | 11.5 |
| Week 44 | 2.5 | 9.7 | 11.7 |
| Week 48 | 3.8 | 11.3 | 10.4 |
| Week 52 | 3.2 | 11.5 | 10.6 |
A participant was considered as having achieved the Boolean-based American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) remission at a visit if all of the following 4 criteria were met at that visit: Tender joint count (68 joints) less than or equal to (\<=) 1; Swollen joint count (66 joints) \<=1; CRP \<=1 milligram per deciliter (mg/dL); Patient's Global Assessment of Disease Activity \<=1 on a 0 (very well) to 10 (very poor) VAS. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Percentage of Participants | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Week 2 | 0.2 | 0.4 | 0 |
| Week 4 | 0.2 | 0.4 | 0.7 |
| Week 6 | 0 | 0.9 | 0.9 |
| Week 8 | 0.2 | 1.3 | 1.8 |
| Week 12 | 1.3 | 2.9 | 3.1 |
| Week 16 | 1.6 | 3.2 | 4.7 |
| Week 18 | 0.7 | 3.6 | 4.7 |
| Week 20 | 1.3 | 4.3 | 5.6 |
| Week 24 | 0.9 | 4.3 | 7.0 |
| Week 28 | 1.1 | 5.2 | 6.1 |
| Week 32 | 2.3 | 5.0 | 6.5 |
| Week 36 | 1.3 | 7.0 | 7.9 |
| Week 40 | 0.9 | 5.9 | 7.9 |
| Week 44 | 1.4 | 5.7 | 7.9 |
| Week 48 | 1.8 | 7.0 | 7.0 |
| Week 52 | 2.2 | 7.0 | 5.7 |
The Health Assessment Questionnaire-Disability Index (HAQ-DI) score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Negative change reflects an improvement and a positive change reflects a worsening. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Units on a Scale | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Change at Week 2 | -0.075 ± 0.3809 | -0.139 ± 0.3744 | -0.128 ± 0.3939 |
| Change at Week 4 | -0.130 ± 0.4444 | -0.244 ± 0.4498 | -0.254 ± 0.4184 |
| Change at Week 6 | -0.170 ± 0.4657 | -0.318 ± 0.4989 | -0.360 ± 0.4910 |
| Change at Week 8 | -0.172 ± 0.4824 | -0.362 ± 0.5163 | -0.388 ± 0.5163 |
| Change at Week 12 | -0.191 ± 0.5055 | -0.387 ± 0.5512 | -0.399 ± 0.5364 |
| Change at Week 16 | -0.201 ± 0.5439 | -0.409 ± 0.5736 | -0.433 ± 0.5489 |
| Change at Week 18 | -0.217 ± 0.5266 | -0.431 ± 0.5744 | -0.464 ± 0.5496 |
| Change at Week 20 | -0.209 ± 0.5275 | -0.429 ± 0.6074 | -0.474 ± 0.5797 |
| Change at Week 28 | -0.232 ± 0.5515 | -0.438 ± 0.5837 | -0.471 ± 0.5763 |
| Change at Week 32 | -0.225 ± 0.5462 | -0.441 ± 0.6017 | -0.483 ± 0.5886 |
| Change at Week 36 | -0.226 ± 0.5585 | -0.444 ± 0.5961 | -0.461 ± 0.5810 |
| Change at Week 40 | -0.230 ± 0.5586 | -0.447 ± 0.5900 | -0.431 ± 0.5921 |
| Change at Week 44 | -0.228 ± 0.5601 | -0.442 ± 0.6182 | -0.456 ± 0.5956 |
| Change at Week 48 | -0.227 ± 0.5727 | -0.447 ± 0.6207 | -0.481 ± 0.6043 |
| Change at Week 52 | -0.225 ± 0.5693 | -0.453 ± 0.6127 | -0.470 ± 0.5959 |
HAQ-DI has 20-question in 8 functional areas: dressing, arising, eating, walking, hygiene, reaching, gripping, and daily living activities, scored from 0=no difficulty to 3=inability to perform task in that area. Overall score computed as sum of domain score divided by number of domains answered. Total possible score range 0= least difficulty to 3= extreme difficulty. AUC of change from baseline in HAQ-DI score is AUC of change from baseline in HAQ-DI score versus time. AUC was calculated based on measurement (observed HAQ-DI score change from baseline) at scheduled visits using trapezoidal rule.Functional status was determined as cumulative measure of HAQ-DI over 1 year by using AUC of change from baseline in HAQ-DI score through week 52. Decreases in AUC of change from baseline in HAQ-DI means greater average improvement in physical function over time. Participants analyzed according to randomized treatment groups they were assigned, regardless of treatments they actually received.
| Units on a Scale*Day | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Week 0 Through Week 24 | -28.85 ± 69.783 | -57.99 ± 76.384 | -61.71 ± 75.189 |
| Week 0 Through Week 52 | -73.55 ± 170.636 | -145.30 ± 184.630 | -153.03 ± 180.633 |
HAQ-DI response was defined as change of less than -0.22 from baseline in HAQ-DI score. The HAQ-DI score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Percentage of Participants | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Week 2 | 34.4 | 40.6 | 37.0 |
| Week 4 | 38.1 | 49.2 | 52.2 |
| Week 6 | 42.4 | 56.2 | 58.0 |
| Week 8 | 44.1 | 56.2 | 61.0 |
| Week 12 | 44.6 | 60.1 | 60.9 |
| Week 16 | 45.5 | 60.9 | 61.9 |
| Week 18 | 45.9 | 62.7 | 65.4 |
| Week 20 | 46.2 | 61.4 | 65.4 |
| Week 24 | 46.9 | 63.0 | 65.4 |
| Week 28 | 47.8 | 64.8 | 63.4 |
| Week 32 | 46.9 | 62.8 | 63.7 |
| Week 36 | 47.3 | 63.9 | 63.7 |
| Week 40 | 47.3 | 63.7 | 61.8 |
| Week 44 | 47.3 | 62.1 | 63.2 |
| Week 48 | 47.3 | 61.8 | 64.6 |
| Week 52 | 47.1 | 63.4 | 64.5 |
HAQ-DI score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Percentage of Participants | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Week 2 | 7.9 | 12.2 | 11.5 |
| Week 4 | 9.9 | 15.6 | 16.3 |
| Week 6 | 9.5 | 18.3 | 21.2 |
| Week 8 | 10.6 | 21.7 | 21.0 |
| Week 12 | 12.2 | 22.8 | 23.3 |
| Week 16 | 13.3 | 24.6 | 26.8 |
| Week 18 | 13.7 | 24.6 | 25.9 |
| Week 20 | 13.1 | 26.0 | 27.5 |
| Week 24 | 13.1 | 25.9 | 27.5 |
| Week 28 | 13.8 | 26.2 | 28.7 |
| Week 32 | 13.7 | 26.0 | 28.7 |
| Week 36 | 13.7 | 27.5 | 27.5 |
| Week 40 | 13.7 | 27.3 | 26.2 |
| Week 44 | 13.1 | 27.8 | 27.6 |
| Week 48 | 13.8 | 28.2 | 30.0 |
| Week 52 | 12.4 | 27.5 | 29.3 |
vdH-S score is defined as a measurement of progression in structural damage. It is the sum of joint erosion (32 joints of the hands and 12 joints of the feet) score and joint space narrowing (JSN) (30 joints of the hands and 12 joints of the feet) score. The joint erosion assessment is scored according to the surface area involved, from 0 to 5, with 0 indicating no erosion and 5 indicating complete collapse of bone whereas the JSN assessment including subluxation, is scored from 0 (normal) to 4 (bony ankylosis or complete luxation). The total score ranges from 0 (best) to 448 (worst) with higher scores indicating more joint damage. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Units on a Scale | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Score at Week 24 | 1.96 ± 5.390 | 0.35 ± 2.149 | 0.30 ± 2.165 |
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32\*5) and MAX JES for F- 120 (12\*10 \[5\*2 sides of foot\]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30\*4), and MAX JSS for F-48(12\*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS (i.e., JE score + JSN score) of 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Units on a Scale | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Erosion Score: Change at Week 24 | 1.21 ± 3.348 | 0.10 ± 1.306 | 0.08 ± 1.321 |
| JSN Score: Change at Week 24 | 0.76 ± 2.540 | 0.24 ± 1.404 | 0.21 ± 1.537 |
| Erosion Score: Change at Week 52 | 2.23 ± 5.903 | 0.12 ± 1.809 | 0.08 ± 2.005 |
| JSN Score: Change at Week 52 | 1.46 ± 4.311 | 0.38 ± 1.839 | 0.38 ± 2.184 |
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32\*5) and MAX JES for F- 120 (12\*10 \[5\*2 sides of foot\]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30\*4), and MAX JSS for F-48(12\*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS (i.e., erosion score + JSN score) of 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Units on a Scale | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Change in Hand Erosion Score at Week 24 | 0.74 ± 2.406 | 0.07 ± 0.920 | 0.03 ± 0.966 |
| Change in Hand JSN Score at Week 24 | 0.51 ± 1.818 | 0.16 ± 1.025 | 0.16 ± 1.021 |
| Change in Foot Erosion Score at Week 24 | 0.46 ± 1.459 | 0.03 ± 0.682 | 0.05 ± 0.754 |
| Change in Foot JSN Score at Week 24 | 0.25 ± 1.207 | 0.09 ± 0.722 | 0.06 ± 1.152 |
| Change in Hand Erosion Score at Week 52 | 1.43 ± 4.378 | 0.09 ± 1.296 | 0.03 ± 1.312 |
| Change in Hand JSN Score at Week 52 | 0.98 ± 3.196 | 0.25 ± 1.378 | 0.28 ± 1.808 |
| Change in Foot Erosion Score at Week 52 | 0.80 ± 2.460 | 0.03 ± 0.955 | 0.06 ± 1.302 |
| Change in Foot JSN Score at Week 52 | 0.48 ± 2.013 | 0.13 ± 0.929 | 0.10 ± 1.171 |
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S). JE is summary of erosion severity in 32 of hand and 12 of feet joints, scored according to the surface area, from 0 (no erosion) to 5 (complete collapse of bone) whereas the JSN is summary of severity of 30 of hand and 12 of feet joints, scored according to the subluxation from 0 (normal) to 4 (bony ankylosis or complete luxation). The SDC is smallest change in score that is considered to be assessed correctly based on limits of agreement (that is., above the measurement error). The SDC for change from baseline in vdH-S Score is determined as: SDC=1.96 \* SD / (root 2 \* root k), where SD is the standard deviation of the difference between 2 readers in change from baseline in vdH-S score; k is the number of readers. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Percentage of Participants | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Week 24 | 25.3 | 8.3 | 7.6 |
| Week 52 | 35.5 | 12.1 | 12.0 |
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32\*5) and MAX JES for F- 120 (12\*10 \[5\*2 sides of foot\]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30\*4), and MAX JSS for F-48(12\*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS of (i.e., erosion score + JSN score) 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Percentage of Participants | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Week 24 | 48.4 | 65.8 | 68.8 |
| Week 52 | 45.5 | 59.0 | 62.4 |
vdH-S score measures structural damage progression as sum of joint erosion(JE) and joint space narrowing(JSN) scores(S).JE is summary of erosion severity in 32 of hands(H) and 12 of feet(F) joints, scored as per surface area- from 0 (no erosion) to 5 (complete(CM) collapse of bone). Maximum (MAX) JES for H-160 (32\*5) and MAX JES for F- 120 (12\*10 \[5\*2 sides of foot\]). MAX JES is 280 whereas JSN is summary of severity of 30 of H and 12 of F joints, scored to subluxation from 0(normal) to 4(bony ankylosis or CM luxation). MAX JSNS for H-120(30\*4), and MAX JSS for F-48(12\*4). MAX JSNS is 168.Thus MAX JES-280 combined with MAX JSNS-168 gives worst possible vdH-SS (i.e., JE score + JSN score) of 448. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Units on a Scale | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Reader 1 at Week 24 | 2.06 ± 5.616 | 0.21 ± 2.495 | 0.20 ± 2.773 |
| Reader 2 at Week 24 | 1.65 ± 5.053 | 0.38 ± 1.969 | 0.33 ± 1.830 |
| Reader 1 at Week 52 | 2.99 ± 7.940 | 0.54 ± 3.285 | 0.29 ± 3.325 |
| Reader 2 at Week 52 | 2.65 ± 7.331 | 0.54 ± 2.660 | 0.35 ± 2.184 |
Serum CRP is a marker of systemic inflammation. A negative change from baseline in CRP represents improvement. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Milligram per Deciliter | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Baseline | 2.5148 ± 3.38577 | 2.4145 ± 2.62179 | 2.3952 ± 2.64241 |
| Change at Week 2 | -0.1339 ± 2.86946 | -2.2867 ± 2.44604 | -2.3198 ± 2.64772 |
| Change at Week 4 | -0.2209 ± 2.94279 | -2.2707 ± 2.41525 | -2.3406 ± 2.64584 |
| Change at Week 6 | -0.3432 ± 2.96865 | -2.3124 ± 2.44604 | -2.3451 ± 2.64678 |
| Change at Week 8 | -0.3561 ± 3.05281 | -2.2919 ± 2.41368 | -2.3392 ± 2.65864 |
| Change at Week 12 | -0.4099 ± 3.22085 | -2.3038 ± 2.43828 | -2.3274 ± 2.67383 |
| Change at Week 16 | -0.4890 ± 3.17554 | -2.2841 ± 2.43707 | -2.3166 ± 2.65115 |
| Change at Week 18 | -0.4375 ± 3.48359 | -2.3030 ± 2.45255 | -2.3114 ± 2.65919 |
| Change at Week 20 | -0.4682 ± 3.21483 | -2.2973 ± 2.44855 | -2.2798 ± 2.74939 |
| Change at Week 24 | -0.4610 ± 3.31445 | -2.2974 ± 2.45343 | -2.2891 ± 2.73480 |
| Change at Week 28 | -0.5108 ± 3.34288 | -2.2937 ± 2.45419 | -2.2820 ± 2.73435 |
| Change at Week 32 | -0.5332 ± 3.39542 | -2.2474 ± 2.63824 | -2.2907 ± 2.73375 |
| Change at Week 36 | -0.5128 ± 3.36374 | -2.2515 ± 2.62647 | -2.3085 ± 2.73396 |
| Change at Week 40 | -0.4623 ± 3.46179 | -2.2429 ± 2.64450 | -2.3032 ± 2.73402 |
| Change at Week 44 | -0.4631 ± 4.00446 | -2.2398 ± 2.65898 | -2.2895 ± 2.75035 |
| Change at Week 48 | -0.4372 ± 4.15311 | -2.2561 ± 2.62491 | -2.2944 ± 2.75776 |
| Change at Week 52 | -0.3854 ± 3.96633 | -2.2399 ± 2.64267 | -2.2976 ± 2.73878 |
Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness in minutes (If none was present = 0; If morning stiffness was continuing at the time of assessment or was unusual compared to the recent past, average of duration of stiffness over the past 3 days was reported; If stiffness persisted the entire day, 1440 minutes was recorded). Negative values for this outcome measure represent improvement, i.e. shortening of duration of morning stiffness. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Minutes | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Change at Week 2 | -22.5 ± 184.96 | -35.2 ± 212.94 | -24.0 ± 177.41 |
| Change at Week 4 | -27.2 ± 202.02 | -61.6 ± 213.09 | -45.1 ± 181.13 |
| Change at Week 6 | -35.3 ± 190.54 | -81.0 ± 207.07 | -70.3 ± 206.41 |
| Change at Week 8 | -41.7 ± 171.05 | -84.1 ± 232.34 | -79.6 ± 213.42 |
| Change at Week 12 | -53.2 ± 179.24 | -88.1 ± 220.03 | -89.4 ± 217.48 |
| Change at Week 16 | -52.2 ± 173.24 | -82.2 ± 241.75 | -84.1 ± 224.72 |
| Change at Week 18 | -60.2 ± 191.68 | -84.6 ± 239.43 | -88.5 ± 223.95 |
| Change at Week 20 | -62.0 ± 193.64 | -93.5 ± 234.10 | -90.0 ± 229.08 |
| Change at Week 24 | -63.7 ± 195.58 | -96.7 ± 228.31 | -95.5 ± 234.19 |
| Change at Week 28 | -68.3 ± 195.42 | -95.2 ± 230.36 | -98.0 ± 235.03 |
| Change at Week 32 | -68.9 ± 196.31 | -96.5 ± 230.46 | -96.5 ± 231.25 |
| Change at Week 36 | -68.8 ± 196.90 | -96.5 ± 228.71 | -95.2 ± 226.37 |
| Change at Week 40 | -68.7 ± 197.06 | -95.7 ± 243.78 | -95.9 ± 233.28 |
| Change at Week 44 | -69.9 ± 197.38 | -96.6 ± 232.42 | -97.0 ± 234.63 |
| Change at Week 48 | -69.6 ± 195.50 | -97.8 ± 238.36 | -97.0 ± 230.66 |
| Change at Week 52 | -67.3 ± 196.98 | -99.1 ± 233.82 | -97.7 ± 231.53 |
SF-36 questionnaire is health related quality of life (QOL) instrument with 36 questions with 8 multi-item scales (evaluated limitations in): physical functioning due to health problems; usual role activities due to physical health problems; Bodily pain; General mental health (psychological distress and well-being); usual role activities due to personal or emotional problems; social functioning due to physical or mental health problems; Vitality (energy and fatigue); General health perception. Each 8 scales scored from 0 to 100 with higher scores= better health. Based on scale scores, summary scores, physical component score (PCS) and mental component score (MCS) will be derived. Scoring is derived based on algorithm developed in software provided by developer. Summary MCS and PCS score is also scaled from 0 to 100 with higher scores= better health. Participants were analyzed according to randomized treatment groups they were assigned regardless of treatments they actually received.
| Units on a Scale | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| PCS :Change at Week 24 | 2.290 ± 6.2790 | 5.358 ± 7.3312 | 5.850 ± 7.0677 |
| PCS :Change at Week 52 | 2.423 ± 6.8069 | 5.661 ± 7.7405 | 6.162 ± 7.2277 |
| MCS :Change at Week 24 | 2.892 ± 9.1766 | 4.898 ± 9.6508 | 4.216 ± 9.4819 |
| MCS :Change at Week 52 | 2.690 ± 9.5698 | 5.351 ± 9.6397 | 4.767 ± 9.7991 |
The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) is a questionnaire that assesses self-reported tiredness, weakness, and difficulty conducting usual activities due to fatigue. The questionnaire consists of 13 questions that assess a participant's level of fatigue and tiredness over the last 7 days. Each question is graded on a 5-point scale (0 - 4); and accordingly, the total FACIT-Fatigue scores can range from 0 to 52, with lower score reflecting more fatigue and higher scores reflecting less fatigue. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Percentage of Participants | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Week 8 | 41.0 | 55.8 | 54.9 |
| Week 16 | 42.4 | 58.0 | 58.9 |
| Week 24 | 43.9 | 61.4 | 59.4 |
| Week 36 | 39.7 | 57.8 | 56.2 |
| Week 52 | 41.0 | 59.1 | 60.5 |
The Work Limitations Questionnaire (WLQ) was used to measure the impairment in work-related productivity, with reference to the previous two weeks. Each work-related question is scored from 0 to 4 and the total score ranges from 0-100, with lower scores signifying fewer limitations at work. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Units on a Scale | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Week 8 | -0.812 ± 3.6230 | -1.946 ± 3.8040 | -2.202 ± 3.8437 |
| Week 16 | -0.840 ± 4.6414 | -2.406 ± 4.1403 | -2.600 ± 4.3066 |
| Week 24 | -1.019 ± 4.5328 | -2.765 ± 4.4381 | -2.884 ± 4.5873 |
| Week 36 | -0.940 ± 4.7982 | -2.921 ± 4.4205 | -2.952 ± 4.5640 |
| Week 52 | -0.732 ± 5.0288 | -3.057 ± 4.5290 | -2.936 ± 4.3940 |
The EuroQol Health State Visual Analogue Scale (EQ VAS) records the respondent's self-rated health on a vertical line, VAS where the endpoints are labeled as 0= 'Worst imaginable health state' and 100= 'Best imaginable health state'. The EQ VAS can be used as a quantitative measure of health outcome as judged by the individual respondents. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Units on a Scale | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Change at Week 8 | 5.61 ± 24.415 | 11.64 ± 26.979 | 12.24 ± 26.025 |
| Change at Week 16 | 5.83 ± 26.177 | 14.09 ± 28.581 | 14.36 ± 27.884 |
| Change at Week 24 | 6.71 ± 26.520 | 14.86 ± 28.747 | 16.41 ± 28.830 |
| Change at Week 52 | 8.30 ± 26.144 | 16.80 ± 28.595 | 17.14 ± 28.329 |
The EQ-5D-3L Descriptive System comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 indicating "full health" and 0 representing dead. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received.
| Units on a Scale | Placebo | Sirukumab 50 mg | Sirukumab 100 mg |
|---|---|---|---|
| Change at Week 8 | 0.1041 ± 0.31794 | 0.1734 ± 0.32473 | 0.1647 ± 0.30146 |
| Change at Week 16 | 0.1131 ± 0.33788 | 0.1831 ± 0.34875 | 0.1899 ± 0.31149 |
| Change at Week 24 | 0.1263 ± 0.33539 | 0.1885 ± 0.33867 | 0.2057 ± 0.32081 |
| Change at Week 52 | 0.1255 ± 0.34312 | 0.1950 ± 0.33448 | 0.2007 ± 0.32895 |
Collected over Screening up to Week 120. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Week 0 to Week 120-Placebo | — | 40/556 (7.2%) | 213/556 (38.3%) |
| W0 to W120-Placebo to Sirukumab 50 mg q4w Due to EE/LE or CO | — | 30/242 (12.4%) | 113/242 (46.7%) |
| W0 to W120- Sirukumab 50 mg q4w | — | 111/556 (20%) | 355/556 (63.8%) |
| W0 to W120- Placebo to Sirukumab 100 mg q2w Due to EE/LE or CO | — | 35/241 (14.5%) | 128/241 (53.1%) |
| W0 to W120-Sirukumab 100 mg q2w | — | 97/558 (17.4%) | 353/558 (63.3%) |
| Event | Week 0 to Week 120-Placebo | W0 to W120-Placebo to Sirukumab 50 mg q4w Due to EE/LE or CO | W0 to W120- Sirukumab 50 mg q4w | W0 to W120- Placebo to Sirukumab 100 mg q2w Due to EE/LE or CO | W0 to W120-Sirukumab 100 mg q2w |
|---|---|---|---|---|---|
| PneumoniaInfections and infestations | 0/556 | 1/242 | 11/556 | 1/241 | 10/558 |
| CellulitisInfections and infestations | 1/556 | 0/242 | 7/556 | 2/241 | 5/558 |
| Rheumatoid ArthritisMusculoskeletal and connective tissue disorders | 6/556 | 0/242 | 5/556 | 1/241 | 5/558 |
| SepsisInfections and infestations | 1/556 | 2/242 | 3/556 | 1/241 | 5/558 |
| Radius FractureInjury, poisoning and procedural complications | 0/556 | 1/242 | 1/556 | 0/241 | 5/558 |
| Aspartate Aminotransferase IncreasedInvestigations | 1/556 | 0/242 | 0/556 | 2/241 | 0/558 |
| Blood Bilirubin IncreasedInvestigations | 0/556 | 0/242 | 0/556 | 2/241 | 0/558 |
| Pulmonary EmbolismRespiratory, thoracic and mediastinal disorders | 0/556 | 1/242 | 0/556 | 2/241 | 2/558 |
| PeritonitisInfections and infestations | 1/556 | 2/242 | 3/556 | 0/241 | 0/558 |
| Road Traffic AccidentInjury, poisoning and procedural complications | 0/556 | 2/242 | 0/556 | 0/241 | 0/558 |
| Event | Week 0 to Week 120-Placebo | W0 to W120-Placebo to Sirukumab 50 mg q4w Due to EE/LE or CO | W0 to W120- Sirukumab 50 mg q4w | W0 to W120- Placebo to Sirukumab 100 mg q2w Due to EE/LE or CO | W0 to W120-Sirukumab 100 mg q2w |
|---|---|---|---|---|---|
| Alanine Aminotransferase IncreasedInvestigations | 23/556 | 34/242 | 108/556 | 41/241 | 124/558 |
| Aspartate Aminotransferase IncreasedInvestigations | 17/556 | 20/242 | 63/556 | 23/241 | 84/558 |
| Upper Respiratory Tract InfectionInfections and infestations | 63/556 | 28/242 | 76/556 | 20/241 | 72/558 |
| Injection Site ErythemaGeneral disorders | 6/556 | 11/242 | 50/556 | 31/241 | 70/558 |
| NasopharyngitisInfections and infestations | 53/556 | 16/242 | 70/556 | 19/241 | 67/558 |
| BronchitisInfections and infestations | 27/556 | 17/242 | 48/556 | 13/241 | 36/558 |
| Rheumatoid ArthritisMusculoskeletal and connective tissue disorders | 36/556 | 9/242 | 46/556 | 10/241 | 29/558 |
| HypertensionVascular disorders | 21/556 | 14/242 | 32/556 | 11/241 | 45/558 |
| NeutropeniaBlood and lymphatic system disorders | 5/556 | 9/242 | 40/556 | 8/241 | 34/558 |
| LeukopeniaBlood and lymphatic system disorders | 7/556 | 12/242 | 37/556 | 8/241 | 39/558 |
| Age, Continuous(years) | Placebo | Sirukumab 50 mg q4w | Sirukumab 100 mg q2w | Total |
|---|---|---|---|---|
| Mean | 52.9 ± 11.85 | 52.9 ± 11.8 | 53 ± 11.31 | 52.9 ± 11.65 |
| Sex: Female, Male(Participants) | Placebo | Sirukumab 50 mg q4w | Sirukumab 100 mg q2w | Total |
|---|---|---|---|---|
| Female | 436 | 447 | 452 | 1335 |
| Male | 120 | 110 | 105 | 335 |
| Region of Enrollment(Participants) | Placebo | Sirukumab 50 mg q4w | Sirukumab 100 mg q2w | Total |
|---|---|---|---|---|
| Bulgaria | 5 | 7 | 6 | 18 |
| Canada | 4 | 4 | 3 | 11 |
| Chile | 23 | 21 | 24 | 68 |
| Colombia | 17 | 13 | 11 | 41 |
| Croatia | 4 | 4 | 2 | 10 |
| Japan | 56 | 58 | 54 | 168 |
| Lithuania | 32 | 31 | 35 | 98 |
| Malaysia | 5 | 1 | 1 | 7 |
| Mexico | 33 | 41 | 41 | 115 |
| Poland | 64 | 51 | 54 | 169 |
| Republic of Korea | 21 | 16 | 31 | 68 |
| Romania | 3 | 6 | 6 | 15 |
| Russian Federation | 61 | 67 | 73 | 201 |
| Serbia | 52 | 47 | 45 | 144 |
| South Africa | 40 | 34 | 26 | 100 |
| Taiwan, Province of China | 5 | 14 | 5 | 24 |
| Ukraine | 50 | 50 | 52 | 152 |
| United States | 81 | 92 | 88 | 261 |
Showing the first 100 of 160 sites across 18 countries.
This study is completed, as verified in Dec 2017. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Janssen Research & Development, LLC