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A Study of CNTO 136 (Sirukumab) Administered Subcutaneously in Japanese Patients With Active Rheumatoid Arthritis Unresponsive to Methotrexate or Sulfasalazine

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: NCT01689532
Recruitment Status : Completed
First Posted : September 21, 2012
Results First Posted : October 27, 2016
Last Update Posted : October 27, 2016
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Janssen Pharmaceutical K.K.

Tracking Information
First Submitted Date  ICMJE September 18, 2012
First Posted Date  ICMJE September 21, 2012
Results First Submitted Date  ICMJE July 8, 2016
Results First Posted Date  ICMJE October 27, 2016
Last Update Posted Date October 27, 2016
Study Start Date  ICMJE November 2012
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 6, 2016)
Number of Participants With Treatment Emergent Adverse Events (TEAE) [ Time Frame: Baseline upto Week 68 ]
A TEAE was defined as an event that occurred in the treatment period during which it emerged (that is [i.e.] started or worsened in severity, relation, or other attribute), and even if the event continued to be present.
Original Primary Outcome Measures  ICMJE
 (submitted: September 18, 2012)
  • The number of patients with adverse events [ Time Frame: Up to 68 weeks ]
  • Neutrophil count [ Time Frame: Up to 68 weeks ]
  • Platelet count [ Time Frame: Up to 68 weeks ]
  • Hepatobiliary laboratory abnormalities [ Time Frame: Up to 68 weeks ]
  • Lipid parameter abnormalities [ Time Frame: Up to 68 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2016)
  • Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Response [ Time Frame: At Weeks 16 and 24 ]
    The ACR 20 Response is defined as greater than or equal to (>=) 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS; 0-10 millimeter [mm], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and serum C-Reactive Protein (CRP).
  • Percentage of Participants Achieving American College of Rheumatology (ACR) 50 Response [ Time Frame: At Weeks 16 and 24 ]
    The ACR 50 Response is defined as >=50 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=50 percent improvement in 3 of following 5 assessments: patient's assessment of pain using VAS (0-10 mm, 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by HAQ-DI and serum CRP.
  • Percentage of Participants Achieving American College of Rheumatology (ACR) 70 Response [ Time Frame: At Weeks 16 and 24 ]
    The ACR 70 Response is defined as >=70 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=70 percent improvement in 3 of following 5 assessments: patient's assessment of pain using VAS (0-10 mm, 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by HAQ-DI and CRP.
  • Percentage of Participants Achieving American College of Rheumatology (ACR) 90 Response [ Time Frame: At Weeks 16 and 24 ]
    The ACR 90 Response is defined as >=90 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=90 percent improvement in 3 of following 5 assessments: patient's assessment of pain using VAS (0-10 mm, 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by HAQ-DI and CRP.
  • Percent Change From Baseline in Number of Swollen Joints at Weeks 16 and 24 [ Time Frame: Baseline, Weeks 16 and 24 ]
    Sixty six (66) joints were assessed for swelling by investigator to determine the number of joints that were considered swollen. A negative change from baseline in swollen joint count indicates improvement.
  • Percent Change From Baseline in Number of Tender Joints at Weeks 16 and 24 [ Time Frame: Baseline, Weeks 16 and 24 ]
    Sixty eight (68) joints were assessed for tenderness to determine the number of joints that were considered tender. A negative change from baseline in the tender joint count indicates improvement.
  • Percent Change From Baseline in Patient's Assessment of Pain at Weeks 16 and 24 [ Time Frame: Baseline, Weeks 16 and 24 ]
    Participants assessed their average pain during the past week on a visual analogue scale (VAS). The scale ranged from 0 (no pain) to 10 (the worst possible pain).
  • Percent Change From Baseline in Patient's Global Assessment of Disease Activity at Weeks 16 and 24 [ Time Frame: Baseline, Weeks 16 and 24 ]
    Participants rated their disease activity using the Visual Analog Scale (VAS) on a scale of 0 (very well) to 10 (very poor).
  • Percent Change From Baseline in Physician's Global Assessment of Disease Activity at Weeks 16 and 24 [ Time Frame: Baseline, Weeks 16 and 24 ]
    Physician's Global Assessment of Disease Activity was assessed using the VAS on a scale of 0 (no arthritis activity) to 10 (extremely active arthritis).
  • Percent Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Weeks 16 and 24 [ Time Frame: Baseline, Weeks 16 and 24 ]
    The HAQ-DI is a 20-question instrument that 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 to 3 (0=no difficulty and 3=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. Here, 'n' signifies those participants who were evaluable for the specific timepoint.
  • Percent Change From Baseline in C-Reactive Protein (CRP) at Weeks 16 and 24 [ Time Frame: Baseline, Weeks 16 and 24 ]
    Serum CRP is a marker of systemic inflammation. A negative percent change from baseline in CRP represents improvement.
  • Percentage of Participants Who Achieved Major Clinical Response at Week 52 [ Time Frame: Week 52 ]
    Major clinical response is achieving ACR 70 for 6 continuous months. The ACR 70 Response is defined as >=70 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=70 percent improvement in 3 of following 5 assessments: patient's assessment of pain using VAS (0-10 mm, 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS, (The scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by HAQ-DI and CRP. Achievement of major clinical response reflects an enhanced level of therapeutic efficacy and sustained reduction of signs and symptoms of rheumatoid arthritis (RA).
  • Percentage of Participants With Disease Activity Index Score 28 (CRP) Response at Weeks 16 and 24 [ Time Frame: At Weeks 16 and 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. 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.
  • Percentage of Participants Achieving DAS28 (CRP) Remission at Week 24 [ Time Frame: 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. DAS28 (CRP) remission is defined as a DAS28 (CRP) value of less than (<) 2.6 at any study visit.
  • Change From Baseline in DAS28 (CRP) Score at Weeks 16 and 24 [ Time Frame: Baseline, Weeks 16 and 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.
  • Percentage of Participants With Simplified Disease Activity Index (SDAI) Based ACR/European League Against Rheumatism (EULAR) Remission at Weeks 16, 24 and 52 [ Time Frame: At Weeks 16, 24 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 on VAS, physician's global assessments of disease activity on VAS, and CRP. SDAI-based ACR/EULAR remission is defined as a SDAI value of <=3.3 at the visit.
  • Percentage of Participants With Boolean Based ACR/EULAR Remission at Weeks 16, 24 and 52 [ Time Frame: At Weeks 16, 24 and 52 ]
    The Boolean based ACR/EULAR remission is achieved if all of the following 4 criteria at that visit are met: tender joint count (68 joints) <=1; swollen joint count (66 joints) <=1; CRP <=1 milligram per deciliter (mg/dL); and patient's global assessment of disease activity on visual analog scale (VAS) <=1 on a 0 to 10 scale.
  • Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Weeks 16 and 24 [ Time Frame: Baseline, Weeks 16 and 24 ]
    The CDAI score is a derived score combining 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 range is 0-76. Score interpretation: Remission <=2.8; Low Disease Activity CDAI > 2.8 and <=10; Moderate Disease Activity CDAI >10 and <=22; High Disease Activity CDAI > 22.
  • Change From Baseline in Simplified Disease Activity Index (SDAI) Score at Weeks 16 and 24 [ Time Frame: Baseline, Weeks 16 and 24 ]
    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 0-86. Score interpretation: Remission SDAI <=3.3; Low Disease Activity SDAI >3.3 and <=11; Moderate Disease Activity SDAI >11 and <=26; High Disease Activity SDAI >26.
  • Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 16 and 24 [ Time Frame: Baseline, at Week 16 and 24 ]
    The HAQ-DI is a 20-question instrument that assesses the degree of difficulty a participant has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living), each scored from 0 (no difficulty) to 3 (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.
  • Percentage of Participants Achieving HAQ-DI Response at Weeks 16 and 24 [ Time Frame: At Weeks 16 and 24 ]
    The HAQ-DI is a 20-question instrument that assesses the degree of difficulty a participant has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living), each scored from 0 (no difficulty) to 3 (inability to perform a task in that area). HAQ-DI response was defined as change of > -0.22 from baseline in HAQ-DI score.
  • Percentage of Participants Maintaining HAQ-DI Response [ Time Frame: Baseline upto Week 52 ]
    The HAQ-DI is a 20-question instrument that assesses the degree of difficulty a participant has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living), each scored from 0 (no difficulty) to 3 (inability to perform a task in that area). HAQ-DI responders who maintain a change from baseline of > -0.22 in HAQ-DI score.
  • Area Under 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: Baseline, Weeks 24 and 52 ]
    HAQ-DI consisted of 20-question in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living), each scored from 0 (no difficulty) to 3 (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. AUC of change from baseline in HAQ-DI score is the AUC of change from baseline in HAQ-DI score versus the time. AUC was calculated based on the measurement (i.e., observed HAQ-DI score change from baseline) at scheduled visits using the trapezoidal rule. Functional status was determined as a cumulative measure of HAQ-DI over 1 year by using the AUC of the change from baseline in HAQ-DI score through week 52. Decreases in AUC of change from baseline in HAQ-DI indicate a greater average improvement in physical function over time.
  • Change From Baseline in Duration of Morning Stiffness at Weeks 16 and 24 [ Time Frame: Baseline, Weeks 16 and 24 ]
    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.
  • Change From Baseline in Mental Component Scores of 36-Item Short Form Health Survey (SF-36) at Weeks 16, 24 and 52 [ Time Frame: Baseline, Weeks 16, 24 and 52 ]
    The SF-36 is a survey of participant health. It consists of 8 individual domains, which are weighted sums of the questions in their section. The 8 domains are: vitality (VT), physical functioning (PF), bodily pain (BP), general health (GH), Role-Physical (RP), Role-Emotional (RE), social functioning (SF) and mental health (MH). Each of these 8 scales (domains) is scored from 0 to 100 with higher scores indicating better health. Based on the scale scores, the summary mental component score (MCS) is derived. Scales contributing most to the scoring of the SF-36 MCS include the VT, SF, RE and MH. Other domains not noted contribute to the scoring but to a lesser degree. The scoring is derived based on an algorithm that has been developed in a software provided by the developer. The summary MCS score is also scaled from 0 to 100 with higher scores indicating better health.
  • Change From Baseline in Physical Component Scores of 36-Item Short Form Health Survey (SF-36) at Weeks 16, 24 and 52 [ Time Frame: Baseline, Weeks 16, 24 and 52 ]
    The SF-36 is a survey of participant health. It consists of 8 individual domains, which are weighted sums of the questions in their section. The 8 domains are: vitality (VT), physical functioning (PF), bodily pain (BP), general health (GH), Role-Physical (RP), Role-Emotional (RE), social functioning (SF) and mental health (MH). Each of these 8 scales (domains) is scored from 0 to 100 with higher scores indicating better health. Based on the scale scores, the summary physical component score (PCS) is derived. Scales contributing most to the scoring of the SF-36 PCS include the PF, RP, BP and GH. Other domains not noted contribute to the scoring but to a lesser degree. The scoring is derived based on an algorithm that has been developed in a software provided by the developer. The summary PCS score is also scaled from 0 to 100 with higher scores indicating better health.
  • Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) Visual Analog Scale (VAS) Score at Weeks 16, 24 and 52 [ Time Frame: Baseline, Weeks 16, 24 and 52 ]
    The EQ-5D VAS records the participant's self-rated health on a vertical, VAS, with 0 representing the worst imaginable health state and 100 representing the best imaginable health state. The EQ VAS is used as a quantitative measure of health outcome as judged by the individual participant.
  • Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) Index Score at Weeks 16, 24 and 52 [ Time Frame: Baseline, Weeks 16, 24 and 52 ]
    Change from Baseline to end point in Euro Quality of life (Qol)-5 Dimension Questionnaire (EQ-5D). A higher score indicates an improvement in health in the Health Status Index. The EuroQol-5 is a five dimensional health state classification. 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2012)
  • The number of patients who achieve ACR 20 response [ Time Frame: Up to 68 weeks ]
    American College of Rheumatology (ACR) 20 response is at least a 20% improvement in rheumatoid arthritis (RA) symptoms.
  • The number of patients who achieve ACR 50 response [ Time Frame: Up to 68 weeks ]
    ACR 50 response is at least a 50% improvement in RA symptoms.
  • The number of patients who achieve ACR 70 response [ Time Frame: Up to 68 weeks ]
    ACR 70 response is at least a 70% improvement in RA symptoms.
  • The number of patients who achieve ACR 90 response [ Time Frame: Up to 68 weeks ]
    ACR 90 response is at least a 90% improvement in RA symptoms.
  • Major clinical response [ Time Frame: Up to 68 weeks ]
    Major clinical response is achieving ACR 70 for 6 continuous months.
  • Percent improvement from baseline in ACR components [ Time Frame: Up to 68 weeks ]
  • The number of patients with DAS28 (CRP) response [ Time Frame: Up to 68 weeks ]
    The Disease Activity Index (DAS28, using CRP [C-reactive protein]) is a measure of tender and swollen joints (28 joints each) and the patient's assessments of disease activity. A score of higher than 5.1 indicates high disease activity, and a score below 3.2 indicates low disease activity.
  • The number of patients with DAS28 (CRP) remission [ Time Frame: Up to 68 weeks ]
    DAS28 (CRP) remission is defined as a value of <2.6 at a visit.
  • Change from baseline in DAS28 (CRP) [ Time Frame: Up to 68 weeks ]
  • The number of patients with SDAI-based ACR/EULAR remission [ Time Frame: Up to 68 weeks ]
    The Simplified Disease Activity Index (SDAI) is a derived score combining tender joints (28 joints), swollen joints (28 joints), Patient's Global Assessment of Disease Activity (GH), Physician's global assessments of disease activity (PGH), and CRP. SDAI-based ACR/EULAR remission is defined as a SDAI value of ≤ 3.3 at the visit.
  • The number of patients with Boolean-based ACR/EULAR remission [ Time Frame: Up to 68 weeks ]
    Boolean-based ACR/EULAR remission is defined as meeting all of the following 4 criteria at a visit: Tender joint count (68 joints) ≤ 1; Swollen joint count (68 joints) ≤ 1; CRP ≤ 1 mg/dL; Patient's Global Assessment of Disease Activity on VAS ≤ 1 on a 0 to 10 scale.
  • Change from baseline in SDAI [ Time Frame: Up to 68 weeks ]
  • Change from baseline in CDAI [ Time Frame: Up to 68 weeks ]
    The Clinical Disease Activity Index (CDAI) score is a derived score combining tender joints (28 joints), swollen joints (28 joints), GH, and PGH. Scores range from 0 (remission) to 76 (high activity).
  • Change from baseline in HAQ-DI score [ Time Frame: Up to 68 weeks ]
    The Health Assessment Questionnaire - Disability Index (HAQ-DI) 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.
  • AUC of change from baseline in HAQ-DI score from Week 0 through Week 24 and from Week 0 through Week 52 [ Time Frame: Up to 52 weeks ]
    AUC is "area under the curve," an assessment of blood concentration of study agent over time.
  • Proportion of HAQ-DI responders (ie, those who have a change from baseline of > 0.22 in HAQ-DI score) [ Time Frame: Up to 68 weeks ]
  • Proportion of HAQ-DI responders in sirukumab treatment groups who maintain a change from baseline of > 0.22 in HAQ-DI score [ Time Frame: Up to 68 weeks ]
  • Change from baseline in duration of morning stiffness [ Time Frame: Up to 68 weeks ]
  • Change from baseline in physical and mental component scores and in domain scores of SF-36 [ Time Frame: Up to 68 weeks ]
    36-Item Short Form Questionnaire (SF-36) is 8 multi-item scales that are scored from 0 to 100 with higher scores indicating better health.
  • Change from baseline in EQ VAS [ Time Frame: Up to 68 weeks ]
    The EuroQoL Group visual analogue scale (EQ VAS) is a self-rated health assessment. Scores range from 0 (worst health imaginable) to 100 (best health imaginable).
  • Change from baseline in EQ-5D index [ Time Frame: Up to 68 weeks ]
    The EQ-5D is a standardized measure of health status with 3 levels: 1=no problems, 2=some problems, and 3=extreme problems.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of CNTO 136 (Sirukumab) Administered Subcutaneously in Japanese Patients With Active Rheumatoid Arthritis Unresponsive to Methotrexate or Sulfasalazine
Official Title  ICMJE A Multicenter, Randomized, Double-blind, Parallel Group Study of CNTO 136 (Sirukumab), a Human Anti-IL-6 Monoclonal Antibody, Administered Subcutaneously as Monotherapy, in Japanese Subjects With Active Rheumatoid Arthritis Unresponsive to Methotrexate or Sulfasalazine
Brief Summary The purpose of this study is to evaluate the safety and efficacy of sirukumab as a single therapy in Japanese patients with moderately to severely active rheumatoid arthritis (RA) who have not responded to treatment with methotrexate (MTX) or sulfasalazine (SSZ).
Detailed Description This is a randomized (patients will be assigned to treatment by chance), double-blind (study personnel and patients will not know what treatments are being given), multicenter study. The expected duration of the study is 68 weeks. This will include 52 weeks of treatment with study agent with dosing every 2 weeks and 16 weeks of safety follow-up after the last dose. Disease-modifying antirheumatic drugs (DMARDs), including MTX and SSZ, are not permitted from 4 weeks before the first dosing with study agent until Week 24. The use of DMARDs is discouraged at or any time after Week 24; however, patients who have less than 20% improvement from baseline in both swollen and tender joint counts at Week 24 will be allowed to take DMARDs. At or any time after Week 16, the initiation and/or adjustment of oral corticosteroids will be allowed for patients who have less than 20% improvement from baseline in both swollen and tender joint counts at Week 16.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Arthritis, Rheumatoid
Intervention  ICMJE
  • Drug: Sirukumab 100 mg
    Sirukumab 100 mg subcutaneous (SC) injection, at Weeks 0, 2, and every 2 weeks through Week 52.
  • Drug: Sirukumab 50 mg
    Sirukumab 50 mg SC at Weeks 0, 4, and every 4 weeks through Week 52.
  • Drug: Placebo
    Between sirukumab injections, placebo SC at Weeks 2, 6, and every 4 weeks through Week 52.
Study Arms  ICMJE
  • Experimental: Sirukumab 100 mg
    Intervention: Drug: Sirukumab 100 mg
  • Experimental: Sirukumab 50 mg and Placebo
    Interventions:
    • Drug: Sirukumab 50 mg
    • Drug: Placebo
Publications * Takeuchi T, Yamanaka H, Harigai M, Tamamura R, Kato Y, Ukyo Y, Nakano T, Hsu B, Tanaka Y. Sirukumab in rheumatoid arthritis refractory to sulfasalazine or methotrexate: a randomized phase 3 safety and efficacy study in Japanese patients. Arthritis Res Ther. 2018 Mar 7;20(1):42. doi: 10.1186/s13075-018-1536-9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 6, 2016)
122
Original Estimated Enrollment  ICMJE
 (submitted: September 18, 2012)
120
Actual Study Completion Date  ICMJE March 2015
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Be a Japanese man or woman with a diagnosis of rheumatoid arthritis (RA), according to the revised 1987 criteria of the American Rheumatism Association, for at least 3 months before screening
  • Has moderately to severely active RA with at least 6 of 68 tender joints and 6 of 66 swollen joints, at screening and at baseline
  • Has been unresponsive to adequate treatment with methotrexate (MTX), sulfasalazine (SSZ), or combination of MTX or SSZ with other disease-modifying antirheumatic drugs (DMARDs) at screening due to lack of benefit after at least 12 weeks of marketed dose of MTX or SSZ, as assessed by the treating physician. Documented lack of benefit may include inadequate improvement in joint counts, physical function, or overall disease activity
  • If using oral corticosteroids, must be on a stable dose equivalent to <=10 mg/day of prednisolone for at least 2 weeks prior to first dosing with study agent. If currently not using corticosteroids, the patient must not have received oral corticosteroids (by mouth) for at least 2 weeks prior to first dosing with study agent
  • If using nonsteroidal anti-inflammatory drugs (NSAIDs) or other analgesics (pain relievers) for RA, must be on a stable dose for at least 2 weeks prior to first dosing with study agent

Exclusion Criteria:

  • Has a history of intolerance to at least 2 or inadequate response to at least one anti-tumor necrosis factor-alpha (anti-TNF-alpha) agent after 3 months of therapy; has received anti-TNF-alpha (eg, infliximab, golimumab, adalimumab, or etanercept) within 3 months of first study agent dosing
  • 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 dosing or has evidence during screening of abnormally low B-cell level caused by previous B-cell depletion therapy; has used any other biologic therapy for the treatment of RA within 3 months of first study agent dosing; has a history of sirukumab use
  • 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 dosing
  • Has received leflunomide within 24 months before first study agent dosing and has not undergone a drug elimination procedure, unless the M1 metabolite is measured and is undetectable. Drug elimination procedure must be completed prior to obtaining informed consent
  • 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 first study agent dosing; 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 first study agent dosing
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01689532
Other Study ID Numbers  ICMJE CR100876
CNTO136ARA3001 ( Other Identifier: Janssen Pharmaceutical K.K., Japan )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Pharmaceutical K.K.
Study Sponsor  ICMJE Janssen Pharmaceutical K.K.
Collaborators  ICMJE GlaxoSmithKline
Investigators  ICMJE
Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial Janssen Pharmaceutical K.K.
PRS Account Janssen Pharmaceutical K.K.
Verification Date September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP