A Multicenter, Open-Label, Phase II Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Anifrolumab in Pediatric Participants 5 to < 18 Years of Age With Systemic Lupus Erythematosus
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 24
- 试验地点
- 32
- 主要终点
- Maximum observed serum (peak) concentration (Cmax)
研究概览
简要总结
The purpose of this study is to characterize the pharmacokinetics (PK), pharmacodynamics (PD), and safety of subcutaneous (SC) anifrolumab in pediatric participants with moderate to severe systemic lupus erythematosus (SLE) while on background standard of care (SoC) therapy.
详细描述
This is an open-label, multicenter study.
The study includes -
- Screening Period of up to 35 days
- Period A (12-week, open-label treatment period)
- Period B (a possible 12-week dosing regimen adjustment period, if required)
- Treatment Extension Period (up-to-40-week, optional)
- Period C (a 12-week safety follow-up period)
The study intervention (anifrolumab) will be administered subcutaneously using an accessorized pre-filled syringe (APFS) in 2 cohorts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of SLE.
- •Must be receiving at least one of the following SoC regimens for ≥ 4 weeks: oral glucocorticoids (≤1.0 mg/kg/day or ≤ 40 mg/day prednisone equivalent), antimalarials (hydroxychloroquine, chloroquine, or quinacrine), or a single permitted immunosuppressant (azathioprine, mycophenolate mofetil/mycophenolic acid, methotrexate, mizoribine, or tacrolimus) within specified dose limits.
- •Participant must have moderate to severe active SLE disease defined as Systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) ≥ 6 total points.
- •Body weight ≥ 15 kg.
- •Participants must agree to follow study specific contraception requirements as per local regulations.
排除标准
- •Known diagnosis of an IFN mediated autoinflammatory interferonopathy.
- •History of, or current diagnosis of, clinically significant non-SLE related vasculitides.
- •Active, severe SLE-driven renal disease with significant proteinuria.
- •Active severe or unstable neuropsychiatric SLE including but not limited to aseptic meningitis; cerebral vasculitis; myelopathy; demyelination syndromes (ascending, transverse, acute inflammatory demyelinating polyradiculopathy); acute confusional state; impaired level of consciousness; psychosis; acute stroke or stroke syndrome; cranial neuropathy; status epilepticus; cerebellar ataxia; and mononeuritis multiplex.
- •In participants ≥ 11 years of age, a history or evidence of suicidal ideation (severity of 4 [active: method and intent, but no plan] or 5 [active: method, intent, and plan]) within the past 6 months; or any suicidal behavior within the past 12 months or recurrent suicidal behavior in the lifetime of the participant based on an assessment with the Columbia suicide severity rating scale (C-SSRS).
- •History of, or current diagnosis of, catastrophic antiphospholipid syndrome (APS).
- •History of recurrent or opportunistic infection requiring hospitalization and intravenous (IV) antibiotics.
- •Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection, or a positive result for human immunodeficiency virus (HIV) infection.
- •Active hepatitis B and C infection.
- •Any active or recent herpes zoster (HZ) infection that has not completely resolved within 12 weeks prior to study entry or that emerges between screening and Day
- •Any history of severe or recurrent HZ, including non-cutaneous HZ, herpes encephalitis, ophthalmic herpes, or 2 or more prior HZ episodes.
- •Any cytomegalovirus (CMV) or Epstein Barr virus (EBV) infection that has not completely resolved.
- •History of cancer.
- •Prior receipt of anifrolumab.
- •Prior treatment with directly acting cytotoxic B-cell depleting therapeutics.
- •A known history of allergy or reaction to any component of the study intervention formulation or history of anaphylaxis to any human gamma globulin therapy, human proteins, or monoclonal antibodies (mAbs).
研究组 & 干预措施
Cohort 1 (body weight > 40 kg)
Participants with body weight > 40 kg will receive anifrolumab as an injection in APFS.
干预措施: Anifrolumab + APFS (Combination Product)
Cohort 2 (body weight ≥ 15 to ≤ 40 kg)
Participants with body weight ≥ 15 to ≤ 40 kg will receive anifrolumab as an injection in APFS.
干预措施: Anifrolumab + APFS (Combination Product)
结局指标
主要结局
Maximum observed serum (peak) concentration (Cmax)
时间窗: Cohort 1: From Day 1 to Day 8; Cohort 2: From Day 1 to Day 11
To characterize PK (Cmax) of anifrolumab in pediatric participants with SLE following SC administration.
Area under the serum concentration-time curve (AUC)
时间窗: Cohort 1: From Day 1 to Day 8; Cohort 2: From Day 1 to Day 11
To characterize PK (AUC) of anifrolumab in pediatric participants with SLE following SC administration.
Time to maximum plasma concentration (tmax)
时间窗: Cohort 1: From Day 1 to Day 8; Cohort 2: From Day 1 to Day 11
To characterize PK (tmax) of anifrolumab in pediatric participants with SLE following SC administration.
Apparent total body clearance of drug from plasma (CL/F)
时间窗: Cohort 1: From Day 1 to Day 8; Cohort 2: From Day 1 to Day 11
To characterize PK (CL/F) of anifrolumab in pediatric participants with SLE following SC administration.
Trough drug concentration at steady state (Ctrough,ss)
时间窗: At Week 12
To characterize PK (Ctrough,ss) of anifrolumab in pediatric participants with SLE following SC administration.
次要结局
- Suppression of type I IFN 21-gene signature(At Week 12 and 52)
- Change from baseline in anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies(At Week 12 and 52)
- Change from baseline in complement component 3 (C3) levels(At Week 12 and 52)
- Change from baseline in complement component 4 (C4) levels(At Week 12 and 52)
- Change from baseline in total hemolytic complement (CH50) levels(At Week 12 and 52)
- Number and percentage of participants who develop anti drug antibody (ADA) against anifrolumab(From Day 1 to Week 52)