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临床试验/NCT00603525
NCT00603525终止3 期

A Double-blind, Randomized, Placebo Controlled, Parallel Group, Multi-center, Phase III Trial of Ofatumumab Investigating Clinical Efficacy in Patients With Active Rheumatoid Arthritis Who Have Previously Had an Inadequate Response to One or More TNF Antagonist Therapies

GlaxoSmithKline1 个研究点 分布在 1 个国家目标入组 169 人开始时间: 2008年1月最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
3 期
状态
终止
入组人数
169
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
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

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 and safety of ofatumumab in reducing clinical signs and symptoms in adult RA patients who had an inadequate response to TNF-α antagonist therapy.

详细描述

This study consist 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 either ofatumumab or placebo in addition to their background methotrexate treatment. Patients who complete the 24 week Double-blind Period without receiving rescue DMARD treatment will then 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Patients who have completed the Open-label Period or have been withdrawn will then enter a maximum 2 year Follow-up Period, or until there B-cells return to normal or to baseline levels, whichever occurs earlier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

  • •Age ≥ 18 years;
  • •Active disease at the time of screening as defined by:
  • •≥ 8 swollen joints (of 66 joints assessed) and ≥ 8 tender joints (of 68 joints assessed), C-Reactive Protein (CRP) ≥ 1.0 mg/dL or Erythrocyte Sedimentation Rate (ESR) ≥ 22 mm/hour, DAS28≥3.2 (based on ESR);
  • •Inadequate response to previous or current TNF-alpha antagonist treatment;
  • •Treatment with methotrexate (MTX), 7.5-25 mg/week, for at least 12 weeks and at a stable dose for at least 4 weeks.

排除标准

  • •Patients with a history of a rheumatic autoimmune disease other than RA or with significant systemic involvement secondary to RA;
  • •Previous exposure to biologic anti-rheumatic therapies, including investigational compounds;
  • •Exposure to TNF-alpha antagonist treatment < 12 weeks prior to visit 2;
  • •Chronic or ongoing active infectious disease requiring systemic treatment;
  • •Clinically significant cardiac disease; History of significant cerebrovascular disease;
  • •Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral psychiatric disease, or evidence of demyelinating disease;
  • •Known HIV positive; Serologic evidence of Hepatitis B infection; Positive test for Hepatitis C; Positive plasma / white cell JC Virus PCR;
  • •Serum IgG < lower limit of normal;
  • •Breast feeding women or women with a positive pregnancy test at screening;
  • •Current participation in any other interventional clinical study;
  • •Patients known or suspected of not being able to comply with a study protocol.

研究组 & 干预措施

Ofatumumab

Experimental

1000 mL dilution of 35ml of ofatumumab in sterile, pyrogen free 0.9% NaCl. Each treatment cycle consisting of two IV infusion taken 14 days apart. A total of 8 infusion cycles given over a 144 week period

干预措施: Ofatumumab (Drug)

1000 ml Saline

Placebo Comparator

1000 mL sterile, pyrogen free 0.9% NaCl. A treatment cycle consisting of two IV infusion 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

  • 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)
  • 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)
  • Mean DAS28 at Weeks 4, 8, 12, 16, 20, and 24 Using Erythrocyte Sedimentation Rate (ESR) as the Acute Phase Reactant (ARP)(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 the Indicated European League Against Rheumatism (EULAR) Response 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 ESR as the Acute Phase Reactant(Baseline and Weeks 4, 8, 12, 16, 20, and 24)
  • Median of the Largest Integer n, for Which a Participant Met the ACR Criteria Requiring an Improvement of n% (ACRn) at Weeks 4, 8, 12, 16, 20, and 24(Weeks 4, 8, 12, 16, 20, and 24)
  • Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Weeks 4, 8, 12, 16, 20, and 24(Weeks 4, 8, 12, 16, 20, and 24)
  • Change From Baseline in Tender Joint Count at Week 24(Baseline and Week 24)
  • Change From Baseline in Swollen Joint Count 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 Participant-assessed Pain Score Using Visual Analogue Scale (VAS) at Week 24(Baseline and Week 24)
  • Change From Baseline in Participant-assessed Global Disease Score Using VAS at Week 24(Baseline and Week 24)
  • Change From Baseline in the Physician-assessed Global Disease Score Using VAS 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 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)
  • 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)
  • Biomarker Levels for Anti-CCP, RF-IgA, RF-IgG, and RF-IgM at Baseline and Week 4(Baseline and Week 4)
  • Number of Participants With Positive Human Anti-human Antibodies (HAHA) at Week 24(Baseline and Week 24)
  • Change From Baseline in Levels of IgA, IgG and IgM at Week 12 and Week 24(Baseline, Week 12, and Week 24)
  • Minimum 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 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 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)
  • Minimum Change From Baseline 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 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))
  • Time to Retreatment, by Ofatumumab Treatment Course(From Baseline 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))
  • Number of Participants With a CD19+ Cell Count Greater Than or Equal to the Lower Limit of Normal or the Baseline Value at Indicated the 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 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 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 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 Immunoglobulin Values Outside the Reference 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 Positive John Cunningham (JC) Virus Test Results at Baseline or Any Visit Post-baseline During the DB and OL Periods(From basline 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 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))

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (1)

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