A 16-week Double-blind, Placebo-controlled (for Initial 2 Weeks) Randomized Period, Followed by a 24-week Open-label Extension to Assess Magnetic Resonance Image (MRI) - Verified Early Response to Certolizumab Pegol in Subjects With Active Rheumatoid Arthritis (RA)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- UCB Pharma
- 入组人数
- 41
- 试验地点
- 14
- 主要终点
- Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 2 Compared to Baseline for Certolizumab Pegol Arm
研究概览
简要总结
Phase IIIb study to determine early response to Certolizumab Pegol (CZP) with Magnetic Resonance Imaging (MRI) score Outcome Measures in Rheumatoid Arthritis (RA) Clinical Trials (OMERACT) RA MRI Scoring System (RAMRIS) in subjects with RA.
详细描述
To identify the efficacy of Certolizumab Pegol (CZP) on synovitis in dynamic MRI parameters; to make the correlation between European League Against Rheumatism (EULAR), American College of Rheumatology (ACR)p, Disease Activity Score-28 (DAS 28) responses, and Digital XRay (DXR) assessment with reduction of synovitis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with a diagnosis of adult-onset Rheumatoid Arthritis (RA) of at least 3 months duration but no longer than 15 years
- •Subjects with an active adult Rheumatoid Arthritis disease
- •Subjects who have been on Disease-Modifying Anti-Rheumatic Drug (DMARD) therapy for at least 12 weeks
排除标准
- •Subject must not have a secondary, non-inflammatory type of musculoskeletal condition (eg, osteoarthritis or fibromyalgia) that in the investigator's opinion is symptomatic enough to interfere with evaluation of the effect of study drug on the subject's primary diagnosis of Rheumatoid Arthritis (RA)
- •Subject must not have a diagnosis of any other inflammatory arthritis (eg, psoriatic arthritis or ankylosing spondylitis)
- •Subject must not have a history of an infected joint prosthesis at any time with prosthesis still in situ
- •Subject must not have received more than 1 biological agent
- •Subject must not have a history of lymphoproliferative disorder including lymphoma or signs and symptoms suggestive of lymphoproliferative disease at any time
- •Subject with known Tuberculosis (TB) disease, high risk of acquiring TB infection or latent TB infection
- •Subject must not have a known hypersensitivity to any components of the investigational medicinal product
- •Subject must not have contraindications for Magnetic Resonance Image (MRI) and contrast agent
- •Subject must not have any other condition which, in the investigator's judgement, would make them unsuitable for inclusion in the study
研究组 & 干预措施
Placebo followed by Certolizumab Pegol (CZP)
Placebo, saline solution for sc injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40
干预措施: Placebo (Other)
Placebo followed by Certolizumab Pegol (CZP)
Placebo, saline solution for sc injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40
干预措施: Certolizumab Pegol (CZP) 200 mg (Biological)
Placebo followed by Certolizumab Pegol (CZP)
Placebo, saline solution for sc injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40
干预措施: Certolizumab Pegol (CZP) 400 mg (Biological)
Certolizumab Pegol (CZP)
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
干预措施: Certolizumab Pegol (CZP) 200 mg (Biological)
Certolizumab Pegol (CZP)
Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40
干预措施: Certolizumab Pegol (CZP) 400 mg (Biological)
结局指标
主要结局
Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 2 Compared to Baseline for Certolizumab Pegol Arm
时间窗: From Baseline to Week 2
Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.
Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 4 Compared to Baseline for Certolizumab Pegol Arm
时间窗: From Baseline to Week 4
Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.
Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 1 Compared to Baseline for Certolizumab Pegol Arm
时间窗: From Baseline to Week 1
Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.
Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 16 Compared to Baseline for Certolizumab Pegol Arm
时间窗: From Baseline to Week 16
Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.
Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 8 Compared to Baseline for Certolizumab Pegol Arm
时间窗: From Baseline to Week 8
Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.
次要结局
- Percentage of Subjects Meeting the American College of Rheumatology 20 % Criteria (ACR20) at Week 16(From Baseline to Week 16)
- Percentage of Subjects Meeting the American College of Rheumatology 50 % Criteria (ACR50) at Week 16(From Baseline to Week 16)
- Change From Baseline to Week 16 in Bone Mineral Density as Measured by Digital XRay (DXR)(From Baseline to Week 16)
- C-Reactive Protein (CRP) Ratio to Baseline at Week 16(From Baseline to Week 16)
- Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With European League Against Rheumatism (EULAR) Response at Week 16(From Baseline to Week 16)
- Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Maximal Enhancement (ME)(From Baseline to Week 16)
- Change From Baseline to Week 16 in the Disease Activity Score-28 (C-Reactive Protein) (DAS28 (CRP)) Response(From Baseline to Week 16)
- Percentage of Subjects Achieving Disease Activity Score 28 (DAS28 (CRP)) Remission Status (DAS28 (CRP) < 2.6) at Week 16(From Baseline to Week 16)
- Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Initiation Rate of Enhancement (IRE)(From Baseline to Week 16)
- Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Number of Voxels (Nvox) With Plateau and Washout Pattern(From Baseline to Week 16)
- Percentage of Subjects Achieving a Good European League Against Rheumatism (EULAR) Response at Week 16(From Baseline to Week 16)
- Percentage of Subjects Meeting the American College of Rheumatology 70 % Criteria (ACR70) at Week 16(From Baseline to Week 16)
- Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With Disease Activity Score-28 (DAS28 (CRP)) Response at Week 16(From Baseline to Week 16)
- Change From Baseline to Week 16 in Tender Joint Count (TJC)(From Baseline to Week 16)
- Change From Baseline to Week 16 in Swollen Joint Count (SJC)(From Baseline to Week 16)
- Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With American College of Rheumatology 20 % Criteria (ACR20) at Week 16(From Baseline to Week 16)
- Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With American College of Rheumatology 70 % Criteria (ACR70) at Week 16(From Baseline to Week 16)
- Change From Baseline to Week 16 in Health Assessment Questionnaire - Disability Index (HAQ-DI)(From Baseline to Week 16)
- Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With American College of Rheumatology 50 % Criteria (ACR50) at Week 16(From Baseline to Week 16)
- Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With Changes in Hand Bone Mineral Density as Measured by Digital XRay (DXR) at Week 16(From Baseline to Week 16)
- Change From Baseline for the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Synovitis Score at Week 1 Placebo (PBO) Versus Certolizumab Pegol (CZP)(From Baseline to Week 1)
- Change From Baseline for the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Synovitis Score at Week 2 Placebo (PBO) Versus Certolizumab Pegol (CZP)(From Baseline to Week 2)