NCT00655824终止2 期
An Open-label, International, Multi-center, Phase II, Extension Trial Investigating Long-term Efficacy and Safety of Repeated Treatment Courses of Ofatumumab, a Fully Human Monoclonal Anti-CD20 Antibody, in Adult Patients With Active Rheumatoid Arthritis Who Previously Received Ofatumumab or Placebo
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 124
- 试验地点
- 1
- 主要终点
- Time to Treatment Withdrawal
研究概览
简要总结
A 3-year open-label trial for patients who previously participated in Trial Hx-CD20-403 and who fulfill the eligibility criteria for this trial (GEN413) . Th e primary purpose of the trial is to evaluate the long-term effectiveness of repeated courses ( a maximum of 9 treatment courses) of ofatumumab in RA patients who previously received ofatumumab or placebo in Trial Hx-CD20-403.
详细描述
All patients who fulfill the eligibility criteria for this trial , will initiate at least one treatment course of ofatumumab, and depending of subsequent worsening in disease activity will be eligible to received further treatment through the 156 week treatment period: a maximum of a further 8 treatment courses will be given at individualized time intervals . The interval between each treatment course will be at least 16 weeks with the last treatment course given no later than week 130 after baseline (Visit 2A).
After each treatment course the patients will attend their next trial visit 8 weeks after Infusion 1, followed by trial visits every 4 weeks up to Week 24, and subsequently every 8 weeks until the next treatment course.
After completing the Treatment Period or after withdrawing from the Treatment Period prematurely patients will be followed every 12 weeks (Follow-up Period) until CD19+ cells &/or IgG levels have returned to baseline or normal levels.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Previously received ofatumumab or placebo in Trial Hx-CD20-
- •Patients on methotrexate therapy (7.5 - 25 mg/week, p.o., i.m., and/or s.c.).
- •Oral corticosteroids therapy (≤ 10 mg/day prednisolone or equivalent).
- •Active disease at the time of screening as defined by:
- •3 swollen joints (of 28 joints assessed) and ≥ 3 tender joints (of 28 joints assessed), DAS28≥3.2 (based on ESR)
排除标准
- •Use of DMARDs other than methotrexate or exposure to other cell depleting therapy, including investigational compounds < 6 months prior to Visit 2 A.
- •Patients who have received treatment with any non-marketed drug substance within 4 weeks prior to Visit 1 (screening).
- •Breast feeding women or women with a positive pregnancy test at Visit 1 (screening).
- •Received anti-cancer therapy, corticosteroids (intra-articular, i.m., or i.v.), or live/attenuated vaccinations, or exposure to cyclophosphamide, nitrogen mustard, chlorambucil or other alkylating agents < 5 years prior to screening.
- •Past or current malignancy, except for Cervical carcinoma Stage 1B or less, Non-invasive basal cell and squamous cell skin carcinoma, Malignant melanoma with a complete response of a duration of > 10 years, or other cancer diagnoses with a complete response of a duration of > 5 years.
- •Chronic or ongoing active infectious disease requiring systemic treatment.
- •Clinically significant cardiac disease, or history of significant cerebrovascular disease.
- •Significant concurrent, uncontrolled medical conditions, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral psychiatric disease
- •Known or suspected HIV positive, positive serology for hepatitis B (HB), positive test for Hepatitis C, or positive plasma or white cell JC virus (JCV) PCR (either compartment).
- •A circulating IgG level <lower limit of normal.
- •Known hypersensitivity to components of the investigational medicinal product.
- •Patients known or suspected of not being able to comply with a study protocol.
- •Women of child bearing potential not will to use adequate contraception during study
研究组 & 干预措施
Ofatumumab
Experimental
1000 mL dilution of 35mls ofatumumab in sterile, pyrogen free, 0.9% NaCl
干预措施: ofatumumab (Drug)
结局指标
主要结局
Time to Treatment Withdrawal
时间窗: From Baseline up to 144 weeks
Time to treatment withdrawal was defined as the time from the first infusion of ofatumumab until the date of treatment withdrawal. The sponsor discontinued the intravenous route of administration development program for rheumatoid arthritis (RA), and this study was terminated early; hence, this primary endpoint was not evaluated.
次要结局
- Assessment of Total Bilirubin (TB) and Creatinine(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Minimum Change From Baseline in Disease Activity Score Based on 28 Joints (DAS28) Over the Course of Weeks (Wk) 1 to 24 in Each Treatment Course (TC), Assessed by Erythrocyte Sedimentation Rate (ESR; Rate at Which Red Blood Cells Sediment in 1 Hour)(Baseline (last visit prior to dosing in each TC) and last visit of each TC (8 wk post infusion, then every 4 wk until Wk 24; up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Minimum Change From Baseline in DAS28 Over the Course of Weeks 1 to 24 in Each Treatment Course, Based on C-reactive Protein (CRP)(Baseline (last visit prior to dosing in each TC) and last visit of each TC (8 wk post infusion, then every 4 wk until Wk 24; up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Time to Re-treatment in Each Treatment Course(Week 16 to Week 104 of each treatment course (up to 125 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Ofatumumab Serum Concentration(Before infusion and at the end of infusion for each Treatment Course (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next TC; up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial vi)
- Number of Participants With the Indicated Global Disease Assessment Using the VAS(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Number of Participants With the Indicated Pain Score(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Number of Participants With HAHA Response(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Assessment of Heart Rate (HR)(BI and PI A and B for all TCs (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course [up to 156 weeks, follow-up phase]). TCs were individualized based on clinical status and may not correlate to trial visits/wk)
- Number of Participants Achieving American College of Rheumatology (ACR)20(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Number of Participants Achieving ACR50(Baseline of each TCand 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Number of Participants Achieving ACR70(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Number of Participants With the Indicated European League Against Rheumatism (EULAR) Response(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Number of Participants in the Indicated Categories of the Health Assessment Questionnaire (HAQ)(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Whole Blood Transcriptional Profiles(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Percentage of Cluster of Differentiation (CD)19+, 4+, 3+, and 8+ B-cell Subsets in the Blood(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- CD19+, CD4+, CD3+, and CD8+ Cell Counts, Measured in mm^3(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Ratio of CD 4+/CD8+(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Number of Participants With Rheumatoid Factor (RA Factor) >13 International Units Per Milliliter(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Number of Participants With Anti-cyclic Citrullinated Peptide Antibody (CCP) >6.9 International Units Per Liter(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Number of Participants With B-Lymphocyte Stimulator (BLyS) >2.49 Micrograms Per Liter(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Number of Participants With Interleukin 6 (IL-6) >11.9 Picograms Per Milliliter(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Assessment of Sodium, Potassium, Chloride, Bicarbonate, Calcium, and Uric Acid(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Assessment of Total Protein (TP) and Albumin(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Assessment of Blood Urea Nitrogen (BUN)(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Assessment of Alanine Aminotranferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl-transferase (GGT)(Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(BI and PI A and B for all TCs (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course [up to 156 weeks, follow-up phase]). TCs were individualized based on clinical status and may not correlate to trial visits/wk)
- Assessment of Body Temperature (BT)(BI and PI A and B for all TCs (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course [up to 156 weeks, follow-up phase]). TCs were individualized based on clinical status and may not correlate to trial visits/wk)
- Number of Participants With Normal and Abnormal Electrocardiogram Readings(8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
- Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK)(8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.)
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