A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Upadacitinib in Subjects With Giant Cell Arteritis: SELECT-GCA
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 429
- 试验地点
- 172
- 主要终点
- Percentage of Participants Achieving Sustained Remission at Week 52
研究概览
简要总结
This study consists of two periods. The objective of Period 1 is to evaluate the efficacy of upadacitinib in combination with a 26-week corticosteroid (CS) taper regimen compared to placebo in combination with a 52-week CS taper regimen, as measured by the proportion of participants in sustained remission at Week 52, and to assess the safety and tolerability of upadacitinib in participants with giant cell arteritis (GCA). The objective of Period 2 is to evaluate the safety and efficacy of continuing versus withdrawing upadacitinib in maintaining remission in participants who achieved sustained remission in Period 1.
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
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of giant cell arteritis (GCA) according to the following criteria:
- •History of erythrocyte sedimentation rate (ESR) >= 50 mm/hour or high sensitivity C-reactive protein (hsCRP)/CRP >=1.0 mg/dL
- •Presence of at least one of the following: Unequivocal cranial symptoms of GCA or Unequivocal symptoms of polymyalgia rheumatica (PMR)
- •Presence of at least one of the following: temporal artery biopsy revealing features of GCA or evidence of large vessel vasculitis by angiography or cross-sectional imaging such as ultrasound, magnetic resonance imaging (MRI), computed tomography (CT) or positron emission tomography (PET).
- •Active GCA, either new onset or relapsing, within 8 weeks of Baseline.
- •Participants must have received treatment with >=40 mg prednisone (or equivalent) at any time prior to Baseline and be receiving prednisone (or equivalent) >= 20 mg once daily (QD) at Baseline.
- •Participants must have GCA that, in the opinion of the investigator, is clinically stable to allow the participant to safely initiate the protocol-defined corticosteroid (CS) taper regimen.
- •Females must either be postmenopausal or permanently surgically sterile or, practicing at least 1 specified method of birth control through the study.
排除标准
- •Prior exposure to any Janus Kinase (JAK) inhibitor.
- •Treatment with an interleukin-6 (IL-6) inhibitor within 4 weeks of study start, or prior treatment with an IL-6 inhibitor and experienced a disease flare during treatment.
- •Use of any of the following systemic immunosuppressant treatments within the specified timeframe prior to study start:
- •Anakinra within 1 week of study start.
- •Methotrexate, hydroxychloroquine, cyclosporine, azathioprine, or mycophenolate within 4 weeks of study start.
- •Oral corticosteroid (CS) for conditions other than GCA within 4 week of study start, or intravenous CS within 4 weeks of study start.
- •Greater than or equal to 8 weeks for leflunomide if no elimination procedure was followed, or adhere to an elimination procedure.
- •Cell-depleting agents or alkylating agents including cyclophosphamide within 6 months of study start.
- •Current or past history of infection including herpes zoster or herpes simplex, human immunodeficiency virus (HIV), active Tuberculosis, active or chronic recurring infection, active hepatitis B or C.
- •Female who is pregnant, breastfeeding, or considering pregnancy during the study.
研究组 & 干预措施
Placebo + 52-week CS taper
Participants received placebo tablets for upadacitinib administered orally once daily (QD) for 52 weeks and a 52-week corticosteroid (CS) taper regimen during Period 1.
干预措施: Corticosteroid (CS) (Drug)
Placebo + 52-week CS taper
Participants received placebo tablets for upadacitinib administered orally once daily (QD) for 52 weeks and a 52-week corticosteroid (CS) taper regimen during Period 1.
干预措施: Placebo (Other)
7.5 mg Upadacitinib + 26-week CS taper
Participants received 7.5 mg upadacitinib tablets administered orally once daily (QD) for 52 weeks and a 26-week corticosteroid (CS) taper regimen during Period 1.
干预措施: Upadacitinib (Drug)
7.5 mg Upadacitinib + 26-week CS taper
Participants received 7.5 mg upadacitinib tablets administered orally once daily (QD) for 52 weeks and a 26-week corticosteroid (CS) taper regimen during Period 1.
干预措施: Corticosteroid (CS) (Drug)
15 mg Upadacitinib + 26-week CS taper
Participants received 15 mg upadacitinib tablets administered orally once daily (QD) for 52 weeks and a 26-week corticosteroid (CS) taper regimen during Period 1.
干预措施: Upadacitinib (Drug)
15 mg Upadacitinib + 26-week CS taper
Participants received 15 mg upadacitinib tablets administered orally once daily (QD) for 52 weeks and a 26-week corticosteroid (CS) taper regimen during Period 1.
干预措施: Corticosteroid (CS) (Drug)
Placebo + 52-week CS taper -> Placebo
Participants who achieved sustained remission for at least 24 weeks prior to the Week 52 visit (at the end of Period 1) OR at remission at the Week 52 visit only who were assigned to placebo tablets for upadacitinib administered orally once daily (QD) in Period 1 continued to receive placebo tablets for upadacitinib administered orally once daily (QD) in Period 2.
干预措施: Placebo (Other)
7.5 mg Upadacitinib + 26-week CS taper -> 7.5 mg Upadacitinib
Participants received 7.5 mg upadacitinib tablets administered orally once daily (QD) in Period 2.
干预措施: Upadacitinib (Drug)
7.5 mg Upadacitinib + 26-week CS taper -> Placebo
Participants received placebo tablets for upadacitinib administered orally once daily (QD) in Period 2.
干预措施: Placebo (Other)
15 mg Upadacitinib + 26-week CS taper -> 15 mg Upadacitinib
Participants received 15 mg upadacitinib tablets administered orally once daily (QD) in Period 2.
干预措施: Upadacitinib (Drug)
15 mg Upadacitinib + 26-week CS taper -> Placebo
Participants received placebo tablets for upadacitinib administered orally once daily (QD) in Period 2.
干预措施: Placebo (Other)
结局指标
主要结局
Percentage of Participants Achieving Sustained Remission at Week 52
时间窗: From Week 12 to Week 52
Sustained remission is defined as having achieved absence of giant cell arteritis (GCA) signs and symptoms from Week 12 through Week 52, and adherence to the protocol-defined corticosteroid (CS) taper regimen.
次要结局
- Percentage of Participants Achieving Sustained Complete Remission From Week 12 Through Week 52(Week 12 through Week 52)
- Cumulative Corticosteroid (CS) Exposure Through Week 52(Baseline up to Week 52)
- Time to First Disease Flare Through Week 52(Baseline up to Week 52)
- Percentage of Participants Who Experience at Least 1 Disease Flare Through Week 52(Baseline up to Week 52)
- Percentage of Participants in Complete Remission at Week 52(At Week 52)
- Percentage of Participants in Complete Remission at Week 24(At Week 24)
- Change From Baseline in the 36-item Short Form Quality of Life Questionnaire (SF-36) Physical Component Summary (PCS) Score at Week 52(Baseline, Week 52)
- Number of Disease Flares Per Participant Through Week 52(Baseline up to Week 52)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) at Week 52(Baseline, Week 52)
- Assessment of Treatment Satisfaction Questionnaire for Medication (TSQM) Patient Global Satisfaction Subscale at Week 52(At Week 52)
- Rate of Corticosteroid-related Adverse Events Though Week 52(Baseline up to Week 52)