A Multicentre, Randomised, Double-Blind, Placebo-controlled, Phase 3 Study Evaluating the Efficacy and Safety of Subcutaneous Anifrolumab in Adult Patients With Systemic Lupus Erythematosus
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 367
- 试验地点
- 141
- 主要终点
- British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response
研究概览
简要总结
The purpose of this study is evaluating the efficacy and safety of SC antifrolumab in adult patients with moderate -to-severe SLE despite receiving standard therapy
详细描述
This is a Phase 3, multicentre, multinational, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of a subcutaneous 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 glucocorticoids, antimalarial, and/or immunosuppressants. The study will be performed in adult participants of 18 to 70 years of age.
Approximately 360 participants receiving SOC treatment will be randomised in a 1:1 ratio to receive a fixed subcutaneous dose of anifrolumab or placebo administered once weekly via an accessorized prefilled syringe and with the primary endpoint evaluated at Week 52. Subjects who complete Week 52 may enter into open-label extension (OLE). All patients who enter the OLE Period will receive a fixed subcutaneous dose of anifrolumab for up to 52 weeks. Study intervention will be administered SC via an accessorised prefilled syringe (aPFS).
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
- Single (Participant)
盲法说明
Double Blind (Participant, Care Provider and Investigator) and OLE
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
- •Patients who have a diagnosis of pediatric or adult SLE according to the ACR 1997 revised criteria for ≥ 24 weeks prior to signing the ICF
- •To be eligible a patient must have SLEDAI-2K ≥ 6 points and "Clinical" SLEDAI-2K score ≥4 points at screening
- •BILAG2004 with at least 1 of the following:
- •BILAG2004 level A disease in ≥ 1 organ system
- •BILAG2004 level B disease in ≥ 2 organ systems
- •Physician's Global Assessment (PGA) score ≥ 1.0 on a 0 to 3 VAS at Screening
- •Antinuclear antibody, and/or Anti-dsDNA and/oranti-Smith positive at Screening,
- •Must be on stable background standard therapy with DMARD, glucocorticoids or anti-malarials alone or in combinations.
排除标准
- •Active severe or unstable neuropsychiatric SLE
- •Active severe SLE-driven renal disease
- •History of any non-SLE disease that has required treatment with oral or parenteral corticosteroids for more than a total of 2 weeks within the last 24 weeks prior to signing the ICF.
- •History of recurrent infection requiring hospitalization and IV antibiotics (eg, 3 or more of the same type of infection over the previous 52 weeks).
- •Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the patient to infection, or a positive result for human immunodeficiency virus (HIV) infection confirmed by central laboratory at Screening.
- •At Screening, confirmed positive test for hepatitis B serology and positive test for hepatitis C antibody
- •Any severe case herpes zoster infection at any time prior to Week 0 (Day 1),
- •Opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years of randomization.
- •History of cancer, apart from:
- •Squamous or basal cell carcinoma of the skin treated with documented success of curative therapy ≥ 3 months prior to Week 0 (Day 1)
- •Cervical cancer in situ treated with apparent success with curative therapy ≥ 1 year prior to Week 0 (Day 1).
研究组 & 干预措施
Placebo
Solution for injection in aPFS
干预措施: Placebo (Drug)
Anifrolumab
Solution for injection in aPFS
干预措施: Medi-546 (Drug)
结局指标
主要结局
British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response
时间窗: At week 52
BICLA response is a composite binary endpoint whereby responders are defined by meeting all of the following criteria: * Improvement from baseline in disease activity as measured by BILAG-2004. Improvement is defined as a reduction of all baseline BILAG-2004 A to B/C/D and baseline BILAG-2004 B to C/D and no BILAG-2004 worsening in other organ systems, where worsening is defined as ≥ 1 new BILAG-2004 A or ≥ 2 new BILAG 2004 B. * No worsening from baseline in SLEDAI-2K, where worsening is defined as an increase from baseline of \> 0 points in SLEDAI-2K. * No worsening from baseline in the patient's lupus disease activity, where worsening is defined as an increase ≥ 0.30 points on a 3-point PGA VAS.
次要结局
- SRI4(At week 52)
- Time to first BICLA response sustained through Week 52(Baseline through to Week 52)
- BICLA response with maintained low (or reduced) use of oral corticosteroid (OCS)(At week 52)
- Time to flare(Baseline through to Week 52)
- Maintained oral corticosteroid (OCS) reduction among patients with baseline OCS ≥10 mg/day.(At week 52)
- Annualized flare rate(Baseline through to Week 52)