Clarification of Abatacept Effects in SLE With Integrated Biologic and Clinical Approaches (The ABC Study)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- British Isles Lupus Assessment Group Index-based Combined Lupus Assessment (BICLA)
研究概览
简要总结
This is a randomized, double blind, placebo controlled trial of abatacept for the treatment of lupus arthritis and other manifestations of lupus. Patients with lupus and at least 3 tender and 3 swollen joints and </= 20 mg prednisone have other background immune suppressants withdrawn at entry. They can elect to receive up to a total of 320 mg depomedrol (in two or more injections) between the screening visit and the visit 2 months after dosing begins. Abatacept (125 mg) or placebo is administered in weekly subcutaneous doses. After 3 months of treatment patients who are not responding may elect to receive open label abatacept with or without additional standard of care therapies. Such patients are considered non responders. The primary endpoint is the British Isles Lupus Assessment Group Index (BILAG)-linked Combined Lupus Assessment (BICLA) which will require a clinically significant improvement in arthritis and other active features of lupus
详细描述
Research Hypothesis: Abatacept is effective in lupus arthritis and this will be discernible in a small trial with robust endpoints which incorporates withdrawal of background immune suppressants
Study Schematic: Abatacept 125 mg or placebo will be given in a 1:1 randomization subcutaneously each week for six months. All patients may elect to continue six more months on open label Abatacept. Background Immune Suppressants will be withdrawn at any time between screening and the first dosing visit. At or after screening, patients may elect 40-160 mg depomedrol shots prn not to exceed 320 mg total up to and including the Month 2 Visit (two months after the first dosing visit) After that, additional steroids or immune suppressants, if necessary, will be allowed but the patient will be considered a non-responder in the primary endpoint at six months on that basis. At of after the 3 month visit patients with significant clinical flare may also elect to receive open label Abatacept but will be considered non-responders in the primary endpoint at six months.
Primary Objective: To compare response rates between Abatacept-Treated and Placebo-Treated Patients with active lupus arthritis in a trial designed with background immune suppressant withdrawal, limited steroid rescue, and a robust, discriminatory endpoint. The trial design and primary endpoint of response by BICLA (defined below) have been pre-tested by us for safety and ability to ensure placebo group non-response, underscoring our powering of the study. This will support a rational decision about further development of abatacept for SLE at minimal cost.
Secondary clinical outcome measures used as endpoints will include: SRI 4/5, changes in joint counts, SLEDAI, BILAG, CLASI, PGA, and LFA REAL measures.
The definitions of the clinical outcome measures are as follows: BICLA: BILAG-based Combined Lupus Assessment, This is defined as British Isles Lupus Assessment Group (BILAG) index scores that were severe at entry (BILAG A scores) improving to a moderate (BILAG B) level (or better) and all features that were moderate at entry improving to a mild level (BILAG C scores) or resolved (BILAG D scores) without increase in any other BILAG feature or SLEDAI scoring (see SLEDAI definition below), as well as no more than 10% worsening in a Physician's Global Assessment or any additional treatments after the protocolized baseline rescue (e.g. no new SLE treatments after the two month visit). SLEDAI stands for the Systemic Lupus Erythematosis Disease Activity Index. SRI 4/5 is defined as SLEDAI improvement by at least 4 points (or 5 points respectively), no increase in BILAG-measured disease activity and no more than 10% worsening in a Physician's Global Assessment (PGA). CLASI stands for the Cutaneous Lupus Erythematosus Disease Area and Severity Index. PGA stands for Physician's Global Assessment. LFA REAL stands for the Lupus Foundation of America Rapid Evaluation of the Activity of Lupus. This instrument is in a pilot phase but will be tested in the ABC study.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed Written Informed Consent
- •Four 1997 revised ACR Classification Criteria for SLE
- •Active polyarticular arthritis meeting at minimum BILAG 2004 B definition with a minimum of 3 tender and 3 swollen joints observed at the screening visit
- •Men and women 18 to 70 years of age.
- •Women of childbearing potential and men with partners of childbearing potential must use an acceptable method of birth control throughout the study
- •Women of childbearing potential must have a negative urine pregnancy test at screening and Study Day 1 (baseline visit) and may not be breast feeding
排除标准
- •Current severe, organ-threatening disease (e.g. acute nephritis appropriate for induction therapy, CNS lupus (excepting chorea, cranial neuropathy, and resolving optic neuritis) or any lupus condition requiring cyclophosphamide, biologic therapy, or IV bolus steroids of >/= 500 mg.
- •Subjects who are incapable of understanding or completing study-related assessments.
- •Subjects with any condition, whether or not related to SLE, which, in the opinion of the investigator, might place a subject at unacceptable risk for participation in the study.
- •Subjects with a history of cancer in the last 5 years, other than non-melanoma skin cell cancers cured by local resection or carcinoma in situ.
- •Subjects who currently abuse drugs or alcohol.
- •Subjects with acute herpes zoster or cytomegalovirus (CMV) within 2 months of screening.
- •Subjects who have received any live vaccines within 3 months of first dose.
- •Subjects with any serious bacterial infection within the last 3 months, unless treated and resolved with antibiotics, or any chronic bacterial infection (eg, chronic pyelonephritis, osteomyelitis, or bronchiectasis).
- •Subjects at risk for tuberculosis (TB).
- •Subjects known to be positive for hepatitis B surface antigen or hepatitis C unless negative by PCR or RIBA
- •Acute hemolytic anemia with hemoglobin < 7.0 g/dL or known change in Hg by 2.0 g/dL within four months
- •WBC < 2500/mm3 (< 3 x 109/L) unless due to chronic stable lupus activity
- •Platelets < 40,000/mm3 (< 3 x 109/L) (If less than 100,000 must have been stable (within a range of 10,000/mm3 ) within two months of screening or in two tests during the screening period.
- •Serum creatinine > 2 times the ULN
- •Serum ALT or AST > 2.5 times the ULN
- •Any other laboratory test results that, in the opinion of the investigator, might place a subject at unacceptable risk for participation in the study.
- •Known allergy/sensitivity to the study agent or carrier.
- •Treatment with investigational drug within 28 days (or 5 terminal half-lives) of the Day 1 dose.
- •Cyclophosphamide within 3 months of Day 1 or bolus IV steroids >/=500 mg within 1 month
- •Prednisone > 20 mg qd after the screening visit
研究组 & 干预措施
Placebo
Patients receive placebo instead of Abatacept in a double blind fashion. Otherwise participation is the same, including that at the time of treatment failure they may elect any standard of care treatment and/or to begin taking open label abatacept but this rescue will define non-response in the primary endpoint at six months.
干预措施: Placebo (Other)
Abatacept
Patients receive Abatacept 125 mg subcutaneously weekly for six months. An optional continuation up until 12 months is allowed. Background immune suppressants are withdrawn at the beginning of the study and the option of depomedrol up to 320 mg total (in divided doses) is allowed at any time up through the visit 2 months after study medication is started. After this additional rescue is allowed with any standard of care treatment and/or open label abatacept (since patients are blinded) but this additional rescue will define non-response in the primary endpoint at six months.
干预措施: Abatacept (Biological)
结局指标
主要结局
British Isles Lupus Assessment Group Index-based Combined Lupus Assessment (BICLA)
时间窗: 6 months
The British Isles Lupus Assessment Group Index is a scoring system for progress of disease activity over the prior month with a scoring system that rates each organ system as "A" or severe, "B" or moderate, "C" or mild vs no activity in the past month. To meet the BICLA endpoint requires all baseline severe features (BILAG A) improving to moderate (BILAG B), mild or resolved, and all baseline BILAG B features improving to mild or resolved without increase in any other feature on either the BILAG or a different measure called the SLEDAI (SLE Disease Activity Index). Furthermore there must be no increase in Physician's Global Assessment or any rescue medications after the month 2 visit. Only those meeting all of these criteria meet the primary endpoint.
次要结局
未报告次要终点