Long-term Safety and Efficacy of Sirukumab in Participants With RA Completing Studies CNTO136ARA3002 or CNTO136ARA3003 (SIRROUND-LTE)
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| ClinicalTrials.gov Identifier: NCT01856309 |
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Recruitment Status :
Completed
First Posted : May 17, 2013
Results First Posted : May 6, 2019
Last Update Posted : May 6, 2019
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Sponsor:
Janssen Research & Development, LLC
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Janssen Research & Development, LLC
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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 |
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 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 : | April 30, 2018 |
| Actual Study Completion Date : | April 30, 2018 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Rheumatoid arthritis
| 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. |
Primary Outcome Measures :
- Percentage of Participants With Serious Adverse Events (SAEs) [ Time Frame: From baseline of this LTE study up to 4.3 years ]An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
- Percentage of Participants With Major Adverse Cardiovascular Events (MACE) [ Time Frame: From baseline of this LTE study up to 4.3 years ]MACE was defined as a composite of Myocardial Infarction (MI), stroke, death, hospitalization for unstable angina, and hospitalization for Transient Ischemic Attack (TIA). Adjudication of these events by the Endpoint Adjudication Committee (EAC) was performed in a blinded fashion.
- Percentage of Participants With Malignancies [ Time Frame: From baseline of this LTE study up to 4.3 years ]Percentage of participants with one or more malignancy was reported.
- Percentage of Participants With Serious Infections [ Time Frame: From baseline of this LTE study up to 4.3 years ]Percentage of participants with one or more serious infections was reported.
- Percentage of Participants With Gastrointestinal (GI) Perforations [ Time Frame: From baseline of this LTE study up to 4.3 years ]Percentage of participants with one or more GI perforations was reported. GI perforation is a hole that develops through the entire wall of the stomach, small intestine, large bowel, or gallbladder.
- Percentage of Participants With Hepatobiliary Abnormalities [ Time Frame: From baseline of this LTE study up to 4.3 years ]Percentage of participants with hepatobiliary abnormalities was reported.
- Percentage of Participants With Serious or Moderate/Severe Systemic Hypersensitivity Reactions, or Serum Sickness Adverse Events [ Time Frame: From baseline of this LTE study up to 4.3 years ]Percentage of participants with serious or moderate/severe systemic hypersensitivity reactions, or serum sickness adverse events (AEs) was reported.
Secondary Outcome Measures :
- Percentage of Participants With Toxicity Grade 4 Decrease in Neutrophils [ Time Frame: From baseline of primary studies through end of this LTE study (Approximately 5.3 years) ]Percentage of participants with toxicity grade 4 decrease in neutrophils was reported. As per National Cancer Institute's Common Terminology Criteria for Adverse Events, toxicity grade 4 was defined as decrease in neutrophils less than (<) 500 per Cubic Millimeter (mm^3) or < 0.5 * 10^9 per liter.
- Percentage of Participants With Toxicity Grade 4 Decrease in Platelets [ Time Frame: From baseline of primary studies through end of this LTE study (Approximately 5.3 years) ]Percentage of participants with toxicity grade 4 decrease in platelets was reported. As per National Cancer Institute's Common Terminology Criteria for Adverse Events, toxicity grade 4 was defined as decreased in platelets <25000/mm^3 or < 25.0 * 10^9 per liter.
- Percentage of Participants With ALT >= 3*ULN, ALT >= 5*ULN and ALT >= 8*ULN [ Time Frame: From baseline of primary studies through end of this LTE study (Approximately 5.3 years) ]Percentage of participants with Alanine Aminotranserase (ALT) >= 3*Upper Limit of Normal (ULN), ALT >= 5*ULN or ALT >= 8*ULN was reported.
- Percentage of Participants With AST >= 3*ULN, AST >= 5*ULN and AST >= 8*ULN [ Time Frame: From baseline of primary studies through end of this LTE study (Approximately 5.3 years) ]Percentage of participants with Aspartate Aminotransferase (AST) >= 3*ULN, AST >= 5*ULN and AST >= 8*ULN was reported.
- Percentage of Participants With Either ALT >= 3*ULN or AST >= 3*ULN, and Total Bilirubin >= 2*ULN [ Time Frame: From baseline of primary studies through end of this LTE study (Approximately 5.3 years) ]Percentage of participants with either ALT >= 3*ULN or AST >= 3*ULN and total bilirubin >= 2*ULN was reported.
- Percentage of Participants With Normal Total Cholesterol Value at Baseline and at Least 1 Abnormal Value Post-Baseline [ Time Frame: From baseline of primary studies through end of this LTE study (Approximately 5.3 years) ]Percentage of participants with normal total cholesterol value at baseline and at least 1 abnormal value post-baseline was reported. Abnormal total cholesterol value was defined as total cholesterol value more than (>) 200 milligrams per deciliter (mg/dL).
- Percentage of Participants With Normal Low-Density Lipoprotein (LDL) Value at Baseline and at Least 1 Abnormal Value Post-Baseline [ Time Frame: From baseline of primary studies through end of this LTE study (Approximately 5.3 years) ]Percentage of participants with normal LDL value at baseline and at least 1 abnormal value post-baseline was reported. Abnormal LDL value was defined as LDL value > 130 mg/dL.
- Percentage of Participants With Normal High-Density Lipoprotein (HDL) Value at Baseline and at Least 1 Abnormal Value Post-Baseline [ Time Frame: From baseline of primary studies through end of this LTE study (Approximately 5.3 years) ]Percentage of participants with normal HDL value at baseline and at least 1 abnormal value post-baseline was reported. Abnormal HDL value was defined as HDL value < 40 mg/dL.
- Percentage of Participants With Normal Triglyceride Value at Baseline and at Least 1 Abnormal Value Post-Baseline [ Time Frame: From baseline of primary studies through end of this LTE study (Approximately 5.3 years) ]Percentage of participants with normal triglyceride value at baseline and at least 1 abnormal value post-baseline was reported. Abnormal triglyceride value was defined as triglyceride value > 250 mg/dL.
- Percentage of Participants Who Achieved American College of Rheumatology (ACR) 50 Response Through Week 260 [ Time Frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52, 76, 80, 104, 128, 132, 156, 180, 208, 232 and 260 ]ACR 50 response is greater than or equal to (>=) 50 percent (%) improvement in both tender joint count (68) and swollen joint count (66) and >= 50% 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 for efficacy according to assigned treatment groups from the primary studies, regardless of treatments actually received.
- Percentage of Participants With Boolean-Based American College of Rheumatology (ACR) or European League Against Rheumatism (EULAR) Remission Through Week 260 [ Time Frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52, 76, 80, 104, 128, 132, 156, 180, 208, 232 and 260 ]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 (very well ) to 10 (extremely bad) scale. Higher scores indicates worst health condition. Participants were analyzed for efficacy according to the assigned treatment groups from the primary studies, regardless of the treatments they actually received.
- Percentage of Participants With Disease Activity Index Score 28 (CRP) Remission Through Week 260 [ Time Frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52, 76, 80, 104, 128, 132, 156, 180, 208, 232 and 260 ]The Disease Activity Index Score 28 (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. DAS28 (CRP) remission is defined as a DAS28 (CRP) value of less than (<) 2.6 at any study visit. Participants were analyzed for efficacy according to the assigned treatment groups from the primary studies, regardless of the treatments they actually received.
- Change From Baseline in Clinical Disease Activity Index (CDAI) Score Through Week 260 [ Time Frame: Baseline (Week 0 of primary studies), Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52, 76, 80, 104, 128, 132, 156, 180, 208, 232 and 260 ]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 for efficacy according to the assigned treatment groups from the primary studies, regardless of the treatments they actually received.
- Percentage of Participants With Simplified Disease Activity Index Based (SDAI-based) American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) Remission Through Week 260 [ Time Frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52, 76, 80, 104, 128, 132, 156, 180, 208, 232 and 260 ]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. Participants were analyzed for efficacy according to assigned treatment groups from the primary studies, regardless of treatments actually received.
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Through Week 260 [ Time Frame: Baseline (Week 0 of primary studies), Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52, 76, 80, 104, 128, 132, 156, 180, 208, 232 and 260 ]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 for efficacy according to assigned treatment groups from the primary studies, regardless of treatments actually received.
- Percentage of Participants With Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Through Week 260 [ Time Frame: Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52, 76, 80, 104, 128, 132, 156, 180, 208, 232 and 260 ]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 for efficacy according to assigned treatment groups from the primary studies, regardless of treatments actually received.
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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
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): NCT01856309
Locations
Show 201 study locations
Sponsors and Collaborators
Janssen Research & Development, LLC
GlaxoSmithKline
Investigators
| Study Director: | Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC |
Study Documents (Full-Text)
Documents provided by Janssen Research & Development, LLC:
Documents provided by Janssen Research & Development, LLC:
Study Protocol [PDF] October 6, 2016
Statistical Analysis Plan [PDF] April 9, 2019
| Responsible Party: | Janssen Research & Development, LLC |
| ClinicalTrials.gov Identifier: | NCT01856309 |
| Other Study ID Numbers: |
CR102023 CNTO136ARA3004 ( Other Identifier: Janssen Research & Development, LLC ) 2012-001176-10 ( EudraCT Number ) |
| First Posted: | May 17, 2013 Key Record Dates |
| Results First Posted: | May 6, 2019 |
| Last Update Posted: | May 6, 2019 |
| Last Verified: | April 2019 |
| 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:
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Rheumatoid Arthritis Sirukumab CNTO 136 CNTO136ARA3002 |
SIRROUND-D CNTO136ARA3003 SIRROUND-T SIRROUND-LTE |
Additional relevant MeSH terms:
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Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases |
Autoimmune Diseases Immune System Diseases Antibodies, Monoclonal Immunologic Factors Physiological Effects of Drugs |