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A Study of CNTO 136 (Sirukumab), Administered Subcutaneously, in Patients With Active Rheumatoid Arthritis Despite Disease-Modifying Antirheumatic Drug (DMARD) Therapy (SIRROUND-D)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01604343
Recruitment Status : Completed
First Posted : May 23, 2012
Results First Posted : January 11, 2018
Last Update Posted : January 11, 2018
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Arthritis, Rheumatoid Drug: Placebo Drug: Sirukumab Phase 3

Detailed Description:
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.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1670 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Study of CNTO 136 (Sirukumab), a Human Anti-IL-6 Monoclonal Antibody, Administered Subcutaneously, in Subjects With Active Rheumatoid Arthritis Despite DMARD Therapy
Actual Study Start Date : August 15, 2012
Primary Completion Date : September 2, 2015
Study Completion Date : December 6, 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Placebo then Sirukumab 50 mg or Sirukumab 100 mg Drug: Placebo
Form=solution for injection, route=subcutaneous use; every 2 weeks from Week 0 through Week 50.
Drug: Sirukumab
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.
Experimental: Sirukumab 100 mg Drug: Sirukumab
Type=exact, unit=mg, number=100, form=solution for injection, route=subcutaneous use; Weeks 0, 2, and every 2 weeks through Week 104.
Experimental: Sirukumab 50 mg + Placebo Drug: Placebo
Form=solution for injection, route=subcutaneous use; Weeks 2, 6, and every 4 weeks through Week 104.
Drug: Sirukumab
Type=exact, unit=mg, number=50, form=solution for injection, route=subcutaneous use; Weeks 0, 4, and every 4 weeks through Week 104.


Outcome Measures

Primary Outcome Measures :
  1. Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Week 16 [ Time Frame: 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.

  2. Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Score at Week 52 [ Time Frame: Baseline, 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.


Secondary Outcome Measures :
  1. Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 [ Time Frame: Baseline, 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.

  2. Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24 [ Time Frame: 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.

  3. Percentage of Participants With Disease Activity Index Score 28 (DAS28) (C-reactive Protein (CRP) Remission at Week 24 [ Time Frame: 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.

  4. Percentage of Participants With Major Clinical Response (MCR) at Week 52 [ Time Frame: 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.

  5. Percentage of Participants With an American College of Rheumatology (ACR) 20 Response Through Week 52 [ Time Frame: Week 2, 4, 6, 8, 12, 18, 20, 24, 28, 32, 36, 40, 44, 48, and 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.

  6. Percentage of Participants With an American College of Rheumatology (ACR) 50 Response [ Time Frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 28, 32, 36, 40, 44, 48 and 52 ]
    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.

  7. Percentage of Participants With an American College of Rheumatology (ACR) 70 Response Through Week 52 [ Time Frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 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.

  8. Percentage of Participants With an American College of Rheumatology (ACR) 90 Response Through Week 52 [ Time Frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 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.

  9. Percentage of Participants With Disease Activity Index Score 28 (DAS28) C-reactive Protein (CRP) Response Through Week 52 [ Time Frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 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.

  10. Change From Baseline in Disease Activity Index Score 28 (DAS28) C-reactive Protein (CRP) Through Week 52 [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 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.

  11. Percentage of Participants With Disease Activity Index Score 28 (DAS28) (C-reactive Protein (CRP) Remission Through Week 52 [ Time Frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 28, 32, 36, 40, 44, 48 and 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.

  12. Change From Baseline in Simplified Disease Activity Index (SDAI) Score Through Week 52 [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 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.

  13. Change From Baseline in Clinical Disease Activity Index (CDAI) Score Through Week 52 [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 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.

  14. 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 [ Time Frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 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.

  15. Percentage of Participants With Boolean-based American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) Remission Through Week 52 [ Time Frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 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.

  16. Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Through Week 52 [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 28, 32, 36, 40, 44, 48 and 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.

  17. 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 [ Time Frame: Week 0 Through Week 24 and 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.

  18. Percentage of Participants With Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Through Week 52 [ Time Frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 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.

  19. Percentage of Participants With Health Assessment Questionnaire-Disability Index (HAQ-DI) Score of Less Than or Equal to 0.5 [ Time Frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
    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.

  20. Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Score at Week 24 [ Time Frame: Baseline, 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.

  21. 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 [ Time Frame: Baseline, 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.

  22. 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 [ Time Frame: Baseline, 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.

  23. 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 [ Time Frame: 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.

  24. 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 [ Time Frame: 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 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.

  25. Change From Baseline in Van Der Heijde Modified Sharpe Score (vdH-S Score) by Reader at Weeks 24 and 52 [ Time Frame: Baseline, 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.

  26. Change From Baseline in Serum C-reactive Protein (CRP) Levels Through Week 52 [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 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.

  27. Change From Baseline in the Duration of Morning Stiffness Through Week 52 [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 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.

  28. Change From Baseline in Physical and Mental Component Summary Scores of 36-Item Short Form Health Survey (SF-36) at Weeks 24 and 52 [ Time Frame: Baseline, Week 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.

  29. 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 [ Time Frame: 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.

  30. Change From Baseline in Total Scores of Work Limitations Questionnaire (WLQ) Week 8, 16, 24, 36 and 52 [ Time Frame: Baseline, 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.

  31. Change From Baseline in EuroQol Health State Visual Analogue Scale (EQ VAS) [ Time Frame: Baseline, Week 8, 16, 24, 36 and 52 ]
    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.

  32. Change From Baseline in EuroQol EQ-5D-3L Descriptive System [ Time Frame: at Week 8, 16, 24, and 52 ]
    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.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have a diagnosis of rheumatoid arthritis (RA) for at least 3 months before screening
  • Have moderately to severely active RA with at least 6 of 68 tender joints and 6 of 66 swollen joints, at screening and at baseline
  • Have been unresponsive to single-agent or combination disease-modifying antirheumatic drugs (DMARD) therapy that includes methotrexate (MTX) or sulfasalazine (SSZ) due to lack of benefit after at least 12 weeks of DMARD, as assessed by the treating physician
  • If using oral corticosteroids, must be on a stable dose equivalent to less than or equal to 10 mg/day of prednisone for at least 2 weeks prior to the first administration of study agent. If currently not using corticosteroids, must not have received oral corticosteroids for at least 2 weeks prior to the first administration of study agent
  • If using non nonsteroidal anti-inflammatory drug (NSAIDs) or other analgesics for RA, must be on a stable dose for at least 2 weeks prior to the first administration of study agent
  • If using non-biologic DMARD such as MTX, SSZ, hydroxychloroquine, chloroquine, or bucillamine, must be on a stable dose for at least 4 weeks prior to the first administration of study agent and should have no serious toxic side effects attributable to the DMARD

Exclusion Criteria:

  • Has a history of intolerance to at least 2 or inadequate response to at least 1 anti-tumor necrosis factor alpha agent after 3 months of therapy
  • Has received infliximab, golimumab, adalimumab, or certolizumab pegol within 3 months of the first study agent administration
  • Has received etanercept or yisaipu within 6 weeks of the first study agent administration
  • Has a history of intolerance to tocilizumab that precluded further treatment with it, or inadequate response to 3 months of tocilizumab (anti-IL-6 receptor) therapy
  • Has used B-cell-depleting therapy (eg, rituximab) within 7 months of first study agent administration or have evidence during screening of abnormally low B cell level caused by previous B-cell depletion therapy
  • Has used anakinra within 4 weeks of first study agent administration
  • Has used any other biologic therapy for the treatment of RA within 3 months of the first study agent administration
  • Has received intra-articular (IA), intramuscular (IM), or intravenous (IV) corticosteroids for RA, including adrenocorticotrophic hormone during the 4 weeks prior to first study agent administration-
  • Has received leflunomide within 24 months before the first study agent administration and have not undergone a drug elimination procedure, unless the M1 metabolite is measured and is undetectable. If a drug elimination procedure is performed during screening, the M1 metabolite should be measured and found to be undetectable
  • Has a history of cyclophosphamide or cytotoxic agent use
  • Has received cyclosporine A, azathioprine, tacrolimus, mycophenolate mofetil, oral or parenteral gold, or D-penicillamine within 4 weeks of the first study agent administration
  • Has received an investigational drug (including investigational vaccines) or used an investigational medical device within 3 months or 5 half lives, whichever is longer, before the first study agent administration
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01604343


  Show 160 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
GlaxoSmithKline
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
More Information

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01604343     History of Changes
Other Study ID Numbers: CR100866
CNTO136ARA3002 ( Other Identifier: Janssen Research & Development, LLC )
2010-022242-24 ( EudraCT Number )
U1111-1135-6325 ( Other Identifier: Universal Trial Number )
First Posted: May 23, 2012    Key Record Dates
Results First Posted: January 11, 2018
Last Update Posted: January 11, 2018
Last Verified: December 2017

Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by Janssen Research & Development, LLC:
Active rheumatoid arthritis despite disease-modifying antirheumatic drug therapy
Sirukumab
Human Anti-IL-6 monoclonal antibody

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antibodies, Monoclonal
Antirheumatic Agents
Immunologic Factors
Physiological Effects of Drugs