A Randomized, Double-blind, Placebo Controlled, Multi-centre, Exploratory, Pilot, Phase II Trial of 150mg Atacicept Given Subcutaneously in Combination With Rituximab in Subjects With Rheumatoid Arthritis.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The primary objective of this study is to assess the safety and tolerability of combined treatment with atacicept and rituximab in subjects with active rheumatoid arthritis (RA) receiving re-treatment with rituximab.
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
- •Male and female subjects
- •Greater than and equal to (>=) 18 years of age at the time of Informed Consent
- •Who have rheumatoid arthritis satisfying American College of Rheumatology (ACR) criteria with a disease history of at least 12 months
- •Subjects must have active disease defined by DAS28 >3.2
- •Subjects must have received previous treatment with rituximab and must be candidates for re-treatment with rituximab
- •Female subjects of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for 4 weeks before study day 1 (SD1), during the treatment period and for 12 months after the last dose of rituximab, and must have a negative urine pregnancy test at the screening visit and SD1
- •Other protocol defined inclusion criteria could apply
排除标准
- •Current neurological disease excluding migraine
- •Inflammatory joint disease other than rheumatoid arthritis
- •Any contraindication to rituximab as per national label
- •Use of disease-modifying anti-rheumatic drugs (DMARDs; including methotrexate) for less than 3 months or change in dosing regimen within 28 days before SD1, or methotrexate dose regimen >25 mg/week
- •Participation in any interventional clinical trial within 1 month before SD1 (or within 5 half-lives of the investigated compound before SD1, whichever is longer)
- •Prednisone dose regimen >10 mg/day (or equivalent), or change in steroid dosing regimen within 28 days before SD1
- •Active or latent tuberculosis within the year before screening or major infection requiring hospitalization or intravenous anti-infectives within 28 days before SD1
- •Serum Immunoglobulin G (IgG) below 6 gram per liter (g/L)
- •Known hypersensitivity to atacicept or to any of the components of the formulated atacicpet
- •Known hypersensitivity to rituximab, to any of the components of the formulated rituximab or to murine proteins
- •Breastfeeding or pregnancy
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
Rituximab Plus Atacicept
Rituximab will be administered as an intravenous infusion at a dose of 1000 mg at Weeks 1 and 3, followed by atacicept 150 mg subcutaneously once a week from Week 7 to 32.
干预措施: Rituximab (Biological)
Rituximab Plus Atacicept
Rituximab will be administered as an intravenous infusion at a dose of 1000 mg at Weeks 1 and 3, followed by atacicept 150 mg subcutaneously once a week from Week 7 to 32.
干预措施: Atacicept (Drug)
Rituximab Plus Placebo
Rituximab will be administered as an intravenous infusion at a dose of 1000 mg at Weeks 1 and 3, followed by placebo matched to atacicept subcutaneously once a week from Week 7 to 32.
干预措施: Rituximab (Biological)
Rituximab Plus Placebo
Rituximab will be administered as an intravenous infusion at a dose of 1000 mg at Weeks 1 and 3, followed by placebo matched to atacicept subcutaneously once a week from Week 7 to 32.
干预措施: Placebo matched to atacicept (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Baseline up to Week 64
An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Percentage of Participants With Immunoglobulin G (IgG) Level Less Than 3 Gram Per Liter (g/L)
时间窗: Week 64
Percent Change From Baseline in Anti-pneumococcus Titer at Week 32
时间窗: Baseline, Week 32
Percent change from baseline was calculated as (\[Week 32 value minus baseline value\] multiplied by 100) divided by baseline value.
Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32
时间窗: Baseline, Week 32
Vital signs assessed included blood pressure (systolic and diastolic), pulse and body temperature. Routine safety lab parameters evaluated included red blood cell (RBC), hemoglobin, hematocrit, platelets, mean cellular hemoglobin (MCH), MCH concentration, MCH volume, white blood cell (WBC), lymphocytes, monocytes, eosinophils, basophils, neutrophils, gamma glutamyl transferase (GGT), alanine aminotransferase (ALT), albumin, alkaline phosphatase (AP), aspartate aminotransferase (AST), bilirubin, calcium, creatinine, glucose, potassium, total protein, sodium, uric acid, and blood urea nitrogen. Percent change from baseline was calculated as (\[Week 32 value minus baseline value\] multiplied by 100) divided by baseline value.
Percent Change From Baseline in Anti-tetanus and Anti-diphteria Immunization Titer at Week 32
时间窗: Baseline, Week 32
Percent change from baseline was calculated as (\[Week 32 value minus baseline value\] multiplied by 100) divided by baseline value.
次要结局
- Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP), ACR50-CRP and ACR70-CRP at Week 32(Week 32)
- Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) at Week 32(Baseline, Week 32)
- Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells(Baseline, Week 3, 7, 12, 16, 26 and 32)