A Phase I, Open-label, Single-Arm, Multiple-Dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Anifrolumab in Chinese Participants With Systemic Lupus Erythematosus (SLE)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 15
- 试验地点
- 3
- 主要终点
- Time to maximum observed plasma concentration (Tmax) of anifrolumab.
研究概览
简要总结
To assess the pharmacokinetic parameters of anifrolumab in Chinese participants with active systemic lupus erythematosus(SLE).
详细描述
This is a Phase I, open-label, single-arm, multiple-dose study to evaluate the pharmacokinetics (PK), pharmacodynamics(PD), safety and tolerability profile of intravenously administered anifrolumab in Chinese participants with active SLE despite receiving standard of care (SOC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 to 60 years.
- •Body weight ≥ 40 kg.
- •Confirmed diagnosis of SLE(1997 ACR revised criteria) for ≥ 24 weeks.
- •Must be receiving at least one of the following SOC regimens at screening:
- •oral prednisone monotherapy: ≥ 7.5 mg/day and ≤ 40 mg/day, stable for > 2 weeks;
- •Immunosuppressant(s) with or without OCS: antimalarials, AZA, MMF, MTX, mizoribine permitted; stable for ≥ 8 weeks; maximum dose required;
- •Oral prednisone plus immunosuppressant: start date, stability and maximum dose required.
- •At least one of these antibodies positive: ANA, anti-dsDNA and anti-Smith.
- •At screening, SLEDAI-2K score ≥ 6 points.
- •Chest imaging shows no clinically significant abnormalities (unless due to SLE).
- •No evidence or medical history of active TB, indeterminate TB should be referred to a TB specialist.
- •All participants should use effective contraception methods as protocol requests.
排除标准
- •History or current diagnose of clinically significant non-SLE related vasculitis, severe or unstable neuropsychiatric SLE, active severe SLE-driven renal disease, catastrophic anti-phospholipid syndrome, inflammatory joint or skin disease other than SLE, non-SLE disease that has required treatment of certain dosage of corticosteroid.
- •History or evidence of suicidal ideation or suicidal behavior.
- •History or current diagnose of MTCD or overlap syndrome, unless overlap with RA or MTCD which has developed into SLE.
- •History of recurrent infection requiring hospitalization and IV antibiotics, or opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years of randomization, or clinically significant chronic infection within 3 months, or recent infection still under treatment.
- •History of immunodeficient condition, HIV positive included.
- •Confirmed HBsAg positive, or HBcAb positive and HBV DNA detectable.
- •History of severe case of herpes zoster.
- •Herpes zoster, CMV or EB infection which has not completely resolved within 12 weeks before screening.
- •Acute COVID-19 infection or history of severe COVID-
- •History of cancer, apart from cured squamous or basal cell carcinoma and cervical cancer in situ.
- •Women participants with abnormal pap smear results.
- •Prior receipt of anifrolumab ,or any commercially available biologic agent, or protein kinase inhibitor or any investigational product within 5 half-lives, including B cell-depleting therapy, belimumab, JAK or BTK inhibitor.
- •Known history of allergy to any component of the IP formulation or protein related products.
- •Receipt of any of the following:
- •Intramuscular or IV glucocorticosteroids within 6 weeks;
- •Any live or attenuated vaccine within 8 weeks;
- •Any restricted medication listed in protocol;
- •Blood transfusion within 4 weeks.
- •Certain laboratory test results requirements.
- •Concurrent enrolment in another clinical study.
- •History or current alcohol, drug or chemical abuse within 1 year.
- •Major surgery within 8 weeks or planned elective major surgery.
- •Blood donation or blood loss more than 400 mL within 3 months.
研究组 & 干预措施
Anifrolumab
All eligible participants will receive anifrolumab via intravenous (IV) infusion pump.
干预措施: Anifrolumab (Biological)
结局指标
主要结局
Time to maximum observed plasma concentration (Tmax) of anifrolumab.
时间窗: Day 1 to Day 141
To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.
Maximum observed plasma concentration (Cmax) of anifrolumab.
时间窗: Day 1 to Day 141
To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.
The volume of plasma cleared of drug per unit time (CL) of anifrolumab.
时间窗: Day 1 to Day 141
To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.
Pre-dose trough concentration (Ctrough) of anifrolumab.
时间窗: Day 1 to Day 141
To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.
Area under plasma concentration-time curve over dosing interval (AUC[tau]) of anifrolumab.
时间窗: Day 1 to Day 141
To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.
次要结局
- Incidence of adverse events(From Screening, Day 1 to Day 141)
- 21-gene Type I interferon PD signature(Screening, Day 29, 85, 113, 141)
- Anti-drug antibodies (ADA)(Day 1, 85, 113, 141)
- Incidence of abnormal vital signs(From Screening, Day 1 to Day 141)
- Incidence of abnormal laboratory parameters(Day 29, 57, 85, 113, 141)