Long-term Safety and Efficacy of Sirukumab in Participants With RA Completing Studies CNTO136ARA3002 or CNTO136ARA3003 (SIRROUND-LTE)

Study Description

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Brief Summary:

The purpose of this study is to evaluate the long-term safety and efficacy of CNTO 136 (sirukumab) in participants with rheumatoid arthritis (RA) who are unresponsive to treatment with modifying antirheumatic drugs (DMARDs) or anti-TNF alpha agents.

Condition or disease	Intervention/treatment	Phase
Arthritis, Rheumatoid	Drug: Sirukumab 100 mg; Drug: Sirukumab 50 mg; Drug: Placebo	Phase 3

Detailed Description:

This is a multicenter, long-term study of sirukumab (CNTO 136) that will be conducted in two groups of participants at the same time (parallel-group study). The maximum duration of participation in this study is 208 weeks, followed by approximately 16 weeks of safety and efficacy follow-up after the administration of the final study agent injection of sirukumab. Participant safety will be monitored throughout the study.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	1820 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	A Multicenter, Parallel-group Study of Long-term Safety and Efficacy of CNTO 136 (Sirukumab) for Rheumatoid Arthritis in Subjects Completing Treatment in Studies CNTO136ARA3002 (SIRROUND-D) and CNTO136ARA3003 (SIRROUND-T)
Actual Study Start Date :	August 7, 2013
Actual Primary Completion Date :	May 1, 2018
Estimated Study Completion Date :	February 21, 2020

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Sirukumab 100 mg	Drug: Sirukumab 100 mg; Sirukumab 100 mg subcutaneously (SC) at Weeks 0 (administered as the last dose in CNTO136ARA3002 or CNTO136ARA3003), 2, and every 2 weeks through Week 156 for participants who completed CNTO136ARA3002 and through Week 208 for participants who completed CNTO136ARA3003.
Experimental: Sirukumab 50 mg / placebo	Drug: Sirukumab 50 mg; Sirukumab 50 mg SC at Weeks 0 (administered as the last dose in CNTO136ARA3002 or CNTO136ARA3003), 4, and every 4 weeks through Week 156 for participants who completed CNTO136ARA3002 and through Week 208 for participants who completed CNTO136ARA3003.; Drug: Placebo; Between sirukumab 50 mg injections, placebo SC injections will be administered at Weeks 2, 6, and every 4 weeks until the study becomes open-label, and placebo injections are discontinued.

Outcome Measures

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Primary Outcome Measures :

1. The number of participants with cardiovascular serious adverse events (SAEs) [ Time Frame: Up to 224 weeks ]
2. The number of participants with malignancies [ Time Frame: Up to 224 weeks ]
3. The number of participants with serious infections [ Time Frame: Up to 224 weeks ]
4. The number of participants with gastrointestinal perforations [ Time Frame: Up to 224 weeks ]

Secondary Outcome Measures :

1. Observations of laboratory parameters of interest (neutrophils, platelets, hepatobiliary parameters, and lipid parameters) [ Time Frame: Up to 224 weeks ]
2. Summary of toxicity grading [ Time Frame: Up to 224 weeks ]
3. Proportion of participants who achieve ACR 20 response [ Time Frame: Up to 208 weeks ]
   American College of Rheumatology (ACR) 20 response is a >=20% improvement in rheumatoid arthritis (RA) symptoms.
4. Proportion of participants who achieve ACR 50 response [ Time Frame: Up to 208 weeks ]
   ACR 50 response is a >=50% improvement in RA symptoms.
5. Proportion of participants who achieve ACR 70 response [ Time Frame: Up to 208 weeks ]
   ACR 70 response is a >=70% improvement in RA symptoms.
6. Proportion of participants with DAS28 (CRP) response [ Time Frame: Up to 208 weeks ]
   DAS28 (using CRP [C-reactive protein]) response is improvement from baseline, with >1.2 indicating a good or moderate response and <=0.6 indicating no response.
7. Proportion of participants with DAS28 (CRP) remission [ Time Frame: Up to 208 weeks ]
   DAS28 (using CRP [C-reactive protein]) remission is defined as a value of <2.6 on the Disease Activity Index, a measure of tender and swollen joints and the patient's assessment of disease activity.
8. Change from baseline in DAS28 (CRP) [ Time Frame: Up to 208 weeks ]
   DAS28 (using CRP [C-reactive protein]) is a measure of tender and swollen joints and the patient's assessment of disease activity.
9. Proportion of participants with SDAI-based ACR/EULAR remission [ Time Frame: Up to 208 weeks ]
   The Simplified Disease Activity Index (SDAI)-based ACR/EULAR (European League Against Rheumatism) remission is defined as a SDAI value of <=3.3 at a visit.
10. Proportion of participants with Boolean-based ACR/EULAR remission [ Time Frame: Up to 208 weeks ]
    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 mg/dL; and Patient's Global Assessment of Disease Activity on VAS <=1 on a 0 to 10 scale.
11. Change from baseline in SDAI [ Time Frame: Up to 208 weeks ]
    The Simplified Disease Activity Index (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.
12. Change from baseline in CDAI [ Time Frame: Up to 208 weeks ]
    Clinical Disease Activity Index (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.
13. Change from baseline in HAQ-DI [ Time Frame: Up to 208 weeks ]
    The Health Assessment Questionnaire-Disability Index (HAQ-DI) assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas, each scored from 0 (no difficulty) to 3 (inability to perform a task).
14. Proportion of HAQ-DI responders (ie, those who have a change from baseline of > 0.22 in HAQ-DI score) [ Time Frame: Up to 208 weeks ]
    The Health Assessment Questionnaire-Disability Index (HAQ-DI) assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas, each scored from 0 (no difficulty) to 3 (inability to perform a task).
15. Change from baseline in Physical Component Score (PCS) [ Time Frame: Up to 208 weeks ]
    The Physical Component Score is a summary score with higher scores indicating better health.
16. Change from baseline in Mental Component Score (MCS) [ Time Frame: Up to 208 weeks ]
    The Mental Component Score is a summary score with higher scores indicating better health.
17. Change from baseline in domain scores of 36-item short form health survey (SF-36) [ Time Frame: Up to 208 weeks ]
    The SF-36 is a medical outcome study health measure and consists of 8 multi-item scales that are scored from 0 to 100, with higher scores indicating better health.
18. Change From Baseline in Duration of Morning Stiffness [ Time Frame: Up to 208 weeks ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Completed participation in Studies CNTO136ARA3002 or CNTO136ARA3003
• Signed an informed consent form (ICF) indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study
• Signed an informed consent form (ICF) for pharmacogenetics research (how a person's genes may affect a drug's effects) in order to participate in the optional pharmacogenetics component of this study. Refusal to give consent for this component does not exclude a participant from participation in this clinical study

Exclusion Criteria:

• Withdraws consent and/or discontinues participation in study CNTO136ARA3002 or CNTO136ARA3003
• Is pregnant
• Has active diverticulitis
• Has any condition that, in the opinion of the investigator, would make participation not be in the best interest (eg, compromise the well-being) of the participant or that could prevent, limit, or confound the protocol-specified assessments

Contacts and Locations

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Sponsors and Collaborators

Janssen Research & Development, LLC

GlaxoSmithKline

Investigators

Study Director:	Janssen Research & Development, LLC Clinical Trial	Janssen Research & Development, LLC

More Information

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Responsible Party:	Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:	NCT01856309 History of Changes
Other Study ID Numbers:	CR102023; CNTO136ARA3004 ( Other Identifier: Janssen Research & Development, LLC ); 2012-001176-10 ( EudraCT Number )
First Posted:	May 17, 2013
Last Update Posted:	May 28, 2018
Last Verified:	May 2018

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Janssen Research & Development, LLC:

Rheumatoid Arthritis; Sirukumab; CNTO 136; CNTO136ARA3002	SIRROUND-D; CNTO136ARA3003; SIRROUND-T; SIRROUND-LTE

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases	Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases