A Phase III Randomized, Placebo-Controlled, Double-Blind Clinical Trial to Evaluate the Efficacy and Safety of Subcutaneous Abatacept in Combination With Glucocorticoid Treatment Compared to Glucocorticoid Monotherapy in Adults With Giant Cell Arteritis
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Patients in sustained remission
研究概览
简要总结
To investigate the safety and efficacy of abatacept with steroid treatment in comparison to steroid treatment alone in up to a 28 week taper of steroid treatment to sustain remission of Giant Cell Arteritis in adults.
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, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •New headache (new onset or new type of localized pain in the head)
- •Elevated ESR (≥ 50 mm/h by the Westergren method) or CRP ≥ 1 mg/dL
- •Temporal artery abnormality (i.e. temporal artery tenderness to palpation or decreased pulsation, unrelated to arteriosclerosis of cervical arteries)
- •Temporal artery biopsy showing vasculitis characterized by a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cells
- •Large vessel biopsy showing vasculitis characterized by a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cells or characteristic changes of large vessel stenosis or aneurysm secondary to GCA as seen by arteriography (Magnetic Resonance Imaging/ Magnetic Resonance Angiography), ultrasound (eg, halo sign on color duplex sonography), or CT scan
- •Patients must be treated with prednisone or prednisolone of 20-60 mg/day (prednisone equivalent) and be on a dose between 20-60 mg/day for at least 2 weeks prior to enrollment into the study
排除标准
- •Rheumatic disease other than GCA such as Takayasu's Arteritis, granulomatosis with polyangiitis (Wegener's), rheumatoid arthritis, systemic lupus erythematosus
- •Patients with unilateral blindness (partial or complete) or who have unstable or recurrent visual symptoms attributable to GCA within 4 weeks of randomization
- •Patients with a history of dissection of aorta
- •Patients with a history of myocardial infarction, stroke or transient ischemic attack attributable to GCA within the 3 months of screening
- •Patients who have been treated with intravenous ("pulse") doses of glucocorticoids defined as methylprednisolone > 1000 mg/day if given within 6 weeks of randomization
- •Patients who will require oral or IV glucocorticoid treatment during the trial for conditions other than GCA
- •Patients at risk of tuberculosis
- •Other protocol defined inclusion/exclusion criteria could apply
研究组 & 干预措施
Placebo Monotherapy- 28 Weeks
Glucocorticoid therapy (28-week taper of oral prednisone daily) in combination with placebo subcutaneous injection (1 mL pre-filled syringe weekly)
干预措施: Placebo (Other)
Abatacept Combination Therapy
Abatacept subcutaneous injection (125 mg/mL prefilled syringe weekly) in combination with glucocorticoid therapy (up to 28-week taper of oral prednisone daily)
干预措施: Abatacept (Drug)
Abatacept Combination Therapy
Abatacept subcutaneous injection (125 mg/mL prefilled syringe weekly) in combination with glucocorticoid therapy (up to 28-week taper of oral prednisone daily)
干预措施: Glucocorticoid Treatment (Drug)
Placebo Monotherapy- 28 Weeks
Glucocorticoid therapy (28-week taper of oral prednisone daily) in combination with placebo subcutaneous injection (1 mL pre-filled syringe weekly)
干预措施: Glucocorticoid Treatment (Drug)
Placebo Monotherapy- 52 Weeks
Glucocorticoid therapy (52 week taper of oral prednisone daily) in combination with subcutaneous placebo weekly
干预措施: Placebo (Other)
Placebo Monotherapy- 52 Weeks
Glucocorticoid therapy (52 week taper of oral prednisone daily) in combination with subcutaneous placebo weekly
干预措施: Glucocorticoid Treatment (Drug)
结局指标
主要结局
Patients in sustained remission
时间窗: 40 weeks (week 12 to week 52)
Assessment based on 2-sided stratified Cochran-Mantel-Haenszel (CMH) chi-square test, stratified by baseline glucocorticoid dose group (20-\< 30, 30-\< 40, 40-\< 50 and 50-60 mg/day) and GCA diagnosis (New vs Relapse) at a 5% significance level. Remission is defined as the absence of clinical signs and symptoms of active disease attributable to GCA.
次要结局
- Physician's Global Assessment of Disease Activity according to visual analog scale (VAS)(Up to 52 weeks)
- Subject Assessment of Disease Activity according to visual analog scale (VAS)(Up to 52 weeks)
- Short Form questionnaire-36 (SF-36)(Up to 52 weeks)
- Erythrocyte sedimentation rate (ESR)(52 weeks)
- All adverse events and serious adverse events (AEs/SAEs)(52 weeks)
- Laboratory test abnormalities(52 weeks)
- EuroQOL 5 Dimensions (EQ-5D-3L)(Up to 52 weeks)
- Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue Short Form 8a(Up to 52 weeks)
- Time from Week 12 to first relapse after achieving remission(40 weeks (week 12 to week 52))
- C-reactive protein (CRP)(52 weeks)
- Cmin (μg/mL): Trough level serum concentration of abatacept prior to the administration of the subcutaneous injection(104 weeks)
- Positive abatacept response relative to baseline(52 weeks)
- Cumulative glucocorticoid dose(52 weeks)
- Resource Utilization(Up to 52 weeks)