A Multicentre, Randomised, Double-blind, Placebo-controlled, Phase 3 Study Evaluating the Efficacy and Safety of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 373
- 试验地点
- 1
- 主要终点
- Number of Participants Who Achieved the British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 52
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of an intravenous treatment regimen of anifrolumab versus placebo in adult participants with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE).
详细描述
This is a Phase 3, multicentre, multinational, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of an intravenous treatment regimen of anifrolumab versus placebo in participants with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE) while receiving standard of care (SOC) treatment. Participants must be taking either 1 or any combination of the following: oral corticosteroids (OCS), antimalarial, and/or immunosuppressants. The study will be performed in adult participants aged 18 to 70 years of age.
Approximately 360 participants receiving SOC treatment will be randomised in a 1:1 ratio to receive a fixed intravenous dose of anifrolumab 300 mg or placebo every 4 weeks for a total of 13 doses (Week 0 to Week 48), with the primary endpoint evaluated at the Week 52 visit. Investigational product will be administered as an intravenous infusion (IV) via an infusion pump over a minimum of 30 minutes, every 4 weeks.
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, Investigator)
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
- •Aged 18 through 70 years at the time of screening
- •Diagnosis of paediatric or adult SLE with a diagnosis of SLE according to the ACR 1982 revised criteria ≥24 weeks prior to signing the Informed Consent form (ICF)
- •Currently receiving at least 1 of the following:
- •Where prednisone is the single standard of care medication (ie, the subject is not concurrently receiving any medication listed in inclusion criterion 3(c)), a dose of oral prednisone ≥7.5 mg/day but ≤40 mg/day (or prednisone equivalent) for a minimum of 8 weeks prior to Day
- •In addition, the dose of oral prednisone or prednisone equivalent the subject is taking must be stable for a minimum of 2 weeks prior to randomisation
- •Where prednisone is not the single standard of care medication (ie, the subject is concurrently receiving at least one medication listed in inclusion criterion 3(c), a dose of oral prednisone (≤40 mg/day) (or prednisone equivalent) for a minimum of 2 weeks prior to signing of the ICF. In addition, the dose of oral prednisone or prednisone equivalent the subject is taking must be stable for a minimum of 2 weeks prior to randomisation.
- •Any of the following medications administered for a minimum of 12 weeks prior to signing the informed consent, and at a stable dose for a minimum of 8 weeks prior to signing the informed consent and through Day 1:
- •(i) Azathioprine ≤200 mg/day (ii) Antimalarial (eg, chloroquine, hydroxychloroquine, quinacrine) (iii) Mycophenolate mofetil ≤2 g/day or mycophenolic acid ≤1.44 g/day (iv) Oral, subcutaneous (SC), or intramuscular methotrexate ≤25 mg/week (v) Mizoribine ≤150 mg/day
- •Fulfils at least 4 of the 11 ACR modified 1982 classification criteria for SLE, at least 1 of which must be:
- •Positive antinuclear antibody (ANA) test at screening by immunofluorescent assay (IFA) at the central laboratory with titre ≥1:80; OR
- •Anti-dsDNA antibodies at screening elevated to above normal (including indeterminate), as per the central laboratory; OR
- •Anti-Smith (anti-Sm) antibody at screening elevated to above normal as per the central laboratory
- •At Screening, Disease Activity Adjudication Group confirmation of:
- •SLEDAI-2K Criteria: SLEDAI-2K score ≥6 points and "Clinical" SLEDAI-2K score ≥4 points. The "Clinical" SLEDAI-2K is the SLEDAI-2K assessment score without the inclusion of points attributable to any urine or laboratory results including immunologic measures.
- •Must not have active or latent TB on either chest radiograph or by quantiferon gold test
- •Day 1 "Clinical" SLEDAI-2K score ≥4 points
- •OCS dose stable for at least 2 weeks prior to randomisation
- •Stable SLE SOC treatment at the time of randomisation
- •Women of child-bearing potential must have a negative serum β-hCG test at and negative urine pregnancy test at randomisation prior to administration of investigational product
排除标准
- •Receipt of any investigational product (small molecule or biologic agent) within 4 weeks or 5 half-lives prior to signing of the ICF, whichever is greater
- •Receipt of any of the following:
- •(a) Intra-articular, intramuscular or IV glucocorticosteroids within 6 weeks prior to Day 1
- •History of, or current diagnosis of, a clinically significant non SLE-related vasculitis syndrome.
- •Active severe or unstable neuropsychiatric SLE
- •Active severe SLE-driven renal disease
- •Diagnosis (within 1 year of signing the ICF) of mixed connective tissue disease or any history of overlap syndromes of SLE or SSc.
- •History of, or current, inflammatory joint or skin disease other than SLE
- •History of any non-SLE disease that has required treatment with oral or parenteral corticosteroids for more than 2 weeks within the last 24 weeks prior to signing the ICF
- •Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the subject to infection, or a positive result for human immunodeficiency virus (HIV) infection confirmed by central laboratory at screening. Subjects refusing HIV testing during the screening period will not be eligible for study participation
- •Confirmed positive test for hepatitis B or hepatitis C
- •Any severe herpes infection at any time prior to Week 0 (Day 1)
- •Opportunistic infection requiring hospitalisation or intravenous antimicrobial treatment within 3 years prior to randomization
- •History of cancer, apart from:
- •Squamous or basal cell carcinoma of the skin that has been successfully treated
- •Cervical cancer in situ that has been successfully treated
研究组 & 干预措施
Anifrolumab
Anifrolumab 300 mg intravenous infusion (IV) administered every 4 weeks for a total of 13 doses.
干预措施: Anifrolumab (Biological)
Placebo
Placebo intravenous infusion (IV) administered every 4 weeks for a total of 13 doses.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants Who Achieved the British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 52
时间窗: Baseline; Week 52
Composite endpoint BICLA was defined by meeting all of the following criteria: * Reduction of all baseline British Isles Lupus Assessment Group (BILAG)-2004 A to B/C/D and baseline BILAG-2004 B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by ≥1 new BILAG-2004 A or ≥2 new BILAG-2004 B * No worsening from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), where worsening is defined as an increase from baseline of \>0 points in SLEDAI-2K * No worsening from baseline in participants' lupus disease activity, where worsening is defined by an increase ≥0.30 points on a 3-point Physician's Global Assessment (PGA) visual analogue scale (VAS) * No discontinuation of investigational product * No use of restricted medications beyond the protocol allowed threshold before assessment
次要结局
- Number of Participants Who Achieved and Maintained an Oral Corticosteroids (OCS) Dose of ≤7.5 mg/Day at Week 52 in the Sub-Group of Participants With Baseline OCS ≥10 mg/Day(Week 40; Week 52)
- Number of Participants With a Potentially Clinically Important Change From Baseline in Vital Sign Measurements(Baseline to end of study (Maximum of 60 weeks))
- Number of Participants With ≥50% Reduction in Joint Counts at Week 52 in The Sub-group of Participants With ≥6 Swollen and ≥6 Tender Joints at Baseline(Baseline; Week 52)
- Number of Participants With One or More Adverse Events (AEs)(Baseline to end of study (Maximum of 60 weeks))
- Number of Participants With a Potentially Clinically Important Change From Baseline in Clinical Laboratory Tests(Baseline to end of study (Maximum of 60 weeks))
- Number of Participants Who Achieved the British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 52 in the IFN Test-High Sub-group(Baseline; Week 52)
- Number of Participants With One or More Adverse Events of Special Interest (AESIs)(Baseline to end of study (Maximum of 60 weeks))
- Number of Participants With a ≥50% Reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 12 in The Sub-Group of Participants With Baseline CLASI Activity Score of ≥10(Baseline; Week 12)
- Annualised Flare Rate Through 52 Weeks(Baseline to Week 52)