A Double-blind, Randomized, Placebo Controlled, Parallel Group, Multi-center, Phase III Trial of Ofatumumab Investigating Clinical Efficacy in Adult Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate Therapy
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 265
- 试验地点
- 1
- 主要终点
- Number of Participants With a 20% Improvement From Baseline in Their American College of Rheumatology (ACR) Score (ACR20) at Week 24
研究概览
简要总结
This is a phase III, double-blind, randomized, multicenter, and parallel group trial with a duration of 24 weeks, followed by a 120 week Open-label Period. the primary purpose of the study is to demonstrate the efficacy of ofatumumab in reducing clinical signs and symptoms in adult RA patients after a single course of ofatumumab.
详细描述
This study consists of a Double-blind , placebo controlled, and parallel group part with eligible patients enrolled into a 24 week Double-Blind Period, and randomized in a 1:1 ratio to receive ofatumumab (700mg x 2 infusions) or placebo ( saline x 2 infusions) in addition to their background methotrexate treatment. Patients who completed the 24 week Double-Blind period without receiving rescue DMARD treatment will be eligible to proceed into the 120 week Open-Label Period to receive repeat treatment courses with ofatumumab. In the Open-label Period ofatumumab treatment courses will be given at individualized time intervals only if a clinical response has been achieved following the previous treatment course, and followed by a subsequent worsening in disease activity . Patients who have completed the Open-Label Period or have withdrawn will enter a maximum 2 year Follow-up Period, or until their Bcells return to normal or to baseline levels, whichever occurs earlier.
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
- Double (Participant, Investigator)
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
ofatumumab
1000 mL dilution of 35ml of ofatumumab in sterile, pyrogen free 0.9% NaCl. Each Treatment Cycle consisting of two 700mg IV infusions taken 14 days apart. A total of 8 infusions cycles given over a 144 week period
干预措施: ofatumumab (Drug)
1000 ml Saline
1000 mL dilution of 35ml of ofatumumab in sterile, pyrogen free 0.9% NaCl. Each Treatment Cycle consisting of two IV infusions taken 14 days apart. Only one placebo treatment cycle provided over a 24 week period
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With a 20% Improvement From Baseline in Their American College of Rheumatology (ACR) Score (ACR20) at Week 24
时间窗: Baseline and Week 24
The ACR score was based on improvement from baseline in tender (TJC) and swollen joint counts (SJC). A participant had achieved ACR20 if he experienced \>=20% improvement from baseline in TJC and SJC and a \>=20% improvement from baseline in 3 out of 5 of the following assessments: participant pain assessment on a 100 millimeter (mm) visual analog scale (VAS), participant global assessment on a 100 mm VAS scale, physician global assessment on a 100 mm VAS scale, participant self-assessed disability, and C-reactive protein.
次要结局
- Mean DAS28 at Weeks 4, 8, 12, 16, 20, and 24 Using Erythrocyte Sedimentation Rate (ESR) as the Acute Phase Reactant(Weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in DAS28 at Weeks 4, 8, 12, 16, 20, and 24 Using ESR as the Acute Phase Reactant(Baseline and Weeks 4, 8, 12, 16, 20, and 24)
- Number of Participants With Clinical Remission at Week 24(Week 24)
- Number of Participants With a 20% Improvement From Baseline in Their American College of Rheumatology (ACR) Score (ACR20) at Weeks 4, 8, 12, 16, and 20(Baseline and Weeks 4, 8, 12, 16, and 20)
- Number of Participants With a 50% Improvement From Baseline in Their ACR Score (ACR50) at Weeks 4, 8, 12, 16, 20, and 24(Baseline and Weeks 4, 8, 12, 16, 20, and 24)
- Number of Participants With a 70% Improvement From Baseline in Their ACR Score (ACR70) at Weeks 4, 8, 12, 16, 20, and 24(Baseline and Weeks 4, 8, 12, 16, 20, and 24)
- Median ACRn at Weeks 4, 8, 12, 16, 20, and 24(Weeks 4, 8, 12, 16, 20, and 24)
- Mean Disease Activity Score Based on 28 Joints (DAS28) at Weeks 4, 8, 12, 16, 20, and 24 Using C-reactive Protein (CRP) as the Acute Phase Reactant (APR)(Weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in DAS28 at Weeks 4, 8, 12, 16, 20, and 24 Using CRP as the Acute Phase Reactant(Baseline and Weeks 4, 8, 12, 16, 20, and 24)
- Number of Participants With the Indicated European League Against Rheumatism (EULAR) Response at Weeks 4, 8, 12, 16, 20, and 24 Using CRP as the Acute Phase Reactant(Weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in Swollen Joint Count at Week 24(Baseline and Week 24)
- Change From Baseline in the Participant-assessed Pain Score at Week 24(Baseline and Week 24)
- Number of Participants Classified as Responders at Week 24 According to the Self-Assessed Health Assessment Questionnaire Disability Index (HAQ-DI)(Week 24)
- Change From Baseline in Tender Joint Count at Week 24(Baseline and Week 24)
- Number of Participants With the Indicated European League Against Rheumatism (EULAR) Response at Weeks 4, 8, 12, 16, 20, and 24 Using ESR as the Acute Phase Reactant(Weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in Participant-assessed Global Disease Score at Week 24(Baseline and Week 24)
- Change From Baseline in the Physician-assessed Global Disease Score at Week 24(Baseline and Week 24)
- Change From Baseline in HAQ-DI Score at Week 24(Baseline and Week 24)
- Change From Baseline in CRP at Week 24(Baseline and Week 24)
- Change From Baseline in ESR at Week 24(Baseline and Week 24)
- Change From Baseline in the Short-Form 36 (SF-36v2) Norm-based Scores for Physical Component Summary and Physical Items at Week 24(Baseline and Week 24)
- Change From Baseline in the SF-36v2 Norm-based Scores for Mental Component Summary and Mental Items at Week 24(Baseline and Week 24)
- Change From Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT) Questionnaire Score at Week 24(Baseline and Week 24)
- Change From Baseline in Levels of Anti-CCP, RF-IgA, RF-IgG, and RF-IgM at Week 24(Baseline and Week 24)
- Change From Baseline in Levels of IL-6 and Serum Amyloid A at Week 24(Baseline and Week 24)
- Minimum DAS28-ESR Score During the Double-blind (DB) and Open-label (OL) Periods, by Ofatumumab Treatment Course(First 24 weeks of each treatment course (assessed up to Week 144))
- Minimum DAS28-CRP Score During the DB and OL Periods, by Ofatumumab Treatment Course(First 24 weeks of each treatment course (assessed up to Week 144))
- Minimum Change From Baseline in the DAS28-ESR Score, During the DB and OL Periods, by Ofatumumab Treatment Course(First 24 weeks of each treatment course (assessed up to Week 144))
- Minimum Change From Baseline in the DAS28-CRP Score, During the DB and OL Periods, by Ofatumumab Treatment Course(First 24 weeks of each treatment course (assessed up to Week 144))
- Number of Participants Who Achieved Remission or Low Disease Activity Based on DAS28 (Using ESR), During the DB and OL Periods, by Ofatumumab Treatment Course(First 24 weeks of each treatment course (assessed up to Week 144))
- Number of Participants Who Achieved Remission or Low Disease Activity Based on DAS28 (Using CRP), During the DB and OL Periods, by Ofatumumab Treatment Course(First 24 weeks of each treatment course (assessed up to Week 144))
- Time to Retreatment, by Ofatumumab Treatment Course(From Baseline up to Week 144)
- Number of Participants With Any On-treatment Adverse Event or Serious Adverse Event, During the DB and OL Periods, by Ofatumumab Treatment Course(First treatment (Day 0) until the participant terminated the trial, assessed up to Week 144)
- Number of Participants With a CD19+ Cell Count Greater Than or Equal to the Lower Limit of Normal or the Baseline Value at the Indicated Time Point, During the DB and OL Periods, by Ofatumumab Treatment Course(From baseline up to Week 144)
- Number of Participants With a CD3+ Cell Count Greater Than or Equal to the Lower Limit of Normal or the Baseline Value at the Indicated Time Point, During the DB and OL Periods, by Ofatumumab Treatment Course(From baseline up to Week 144)
- Number of Participants With a CD4+ Cell Count Greater Than or Equal to the Lower Limit of Normal or the Baseline Value at the Indicated Time Point, During the DB and OL Periods, by Ofatumumab Treatment Course(From baseline up to Week 144)
- Number of Participants With a CD8+ Cell Count Greater Than or Equal to the Lower Limit of Normal or the Baseline Value at the Indicated Time Point, During the DB and OL Periods, by Ofatumumab Treatment Course(From baseline up to Week 144)
- Number of Participants With Vital Sign Data Outside the Clinical Concern Range at Baseline or Any Visit Post-baseline, During the DB and OL Periods, by Ofatumumab Treatment Course(From baseline up to Week 144)
- Number of Participants With the Indicated Electrocardiogram (ECG) Findings, During the OL Period(From DB Period completion (Week 24) until the completion of the OL Period, assessed up to Week 144)
- Number of Participants With the Indicated Clinical Chemistry Values of Potential Clinical Concern at Baseline or Any Visit Post-baseline, During the DB and OL Periods, by Ofatumumab Treatment Course(From baseline up to Week 144)
- Number of Participants With the Indicated Hematology Values of Potential Clinical Concern at Baseline or Any Visit Post-baseline, During the DB and OL Periods, by Ofatumumab Treatment Course(From baseline up to Week 144)
- Number of Participants With the Indicated Biomarker Data Outside the Reference Range at Baseline or Any Post-Baseline Visit During the DB and OL Periods by Ofatumumab Treatment Course (TC)(From baseline up to Week 144)
- Number of Participants With Any Serious Adverse Event During the Follow-up Period(From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (or maximum of 2 years from Last Subject Last Visit [LSLV]))
- Number of Participants With Immunoglobulin Values Outside the Reference Range During the Follow-up Period(From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (or maximum of 2 years from LSLV))
- Time to First CD19+ B-cell Repopulation Relative to the First Dose and Last Dose of Ofatumumab(From the first dose of ofatumumab until the last Follow-up Period visit (up to Week 248))
- Number of Participants With a Positive JC Virus Test Result During the Follow-up Period(From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (or maximum of 2 years from LSLV))
- Number of Participants With the Indicated Clinical Chemistry Values of Potential Clinical Concern During the Follow-up Period(From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (maximum of 2 years))
- Number of Participants With the Indicated Hematology Values of Potential Clinical Concern During the Follow-up Period(From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (maximum of 2 years))