A Randomized, Phase 1, Placebo-controlled, Double-blind, Single-dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Subcutaneously and Intravenously Delivered Anifrolumab in Healthy Subjects.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Pharmacokinetics: Observed Maximum Serum Concentration (Cmax) Following Single Dose of Anifrolumab.
研究概览
简要总结
This is a Phase I, Randomized, Placebo-Controlled, Double-Blind Study to Assess the Pharmacokinetics and Safety of anifrolumab following Single-Dose administration to healthy subjects
详细描述
This is a Phase I placebo-controlled study to assess the pharmacokinetics, safety and tolerability of 2 doses of anifrolumab via the subcutaneous (SC) route of administration and 1 dose of anifrolumab via intravenous (IV) route in healthy subjects
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Provision of signed and dated, written informed consent prior to any study specific procedures.
- •Healthy male and/or female subjects aged 18 - 55 years.
- •Females must have a negative pregnancy test at screening.
- •Females with an intact cervix must have documentation of a Pap smear with no documented malignancy.
- •Have a body mass index (BMI) between 18 and 32 kg/m2, inclusive, and weigh at least 50 kg.
- •Must have adequate abdominal adipose tissue for SC injection.
- •No history of latent or active TB prior to screening.
- •A chest radiograph with no evidence of current active infection or old active TB, malignancy, or clinically significant abnormalities within 6 months prior to screening.
排除标准
- •History of any clinically significant disease or disorder which may put the subject at risk .
- •History or presence of hepatic or renal disease.
- •Any clinically significant illness, medical/surgical procedure, or trauma within 8 weeks of participation .
- •Any clinically significant chronic or recent infection requiring hospitalization or treatment with anti-infectives.
- •History of cancer, apart from squamous or basal cell carcinoma of the skin.
- •Any clinically significant lab, vital sign or ECG abnormalities as judged by the investigator.
- •Known history of a primary immunodeficiency,HIV splenectomy or an underlying condition.
- •Any positive result on screening for hepatitis B, hepatitis C or HIV antibody.
- •History of drug abuse within 1 year of participation.
- •Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 4 weeks or 5 half-lives prior to participation.
- •Previous receipt of:
- •Anifrolumab;
- •B cell-depleting therapy (including but not limited to epratuzumab, ocrelizumab, or rituximab) ≤ 52 weeks prior to screening.
- •History of allergy/hypersensitivity to drugs with a similar chemical structure or class to anifrolumab or to any human gamma globulin therapy.
- •Any live or attenuated vaccine within 8 weeks prior to participation.
研究组 & 干预措施
Placebo 300 mg SC injections
300 mg single dose placebo delivered as 2 separate 1 mL SC injections administered serially
干预措施: Anifrolumab placebo SC injection (300mg) (Drug)
Anifrolumab 300 mg SC injections
300 mg single dose anifrolumab delivered as 2 separate 1 mL SC injections administered serially
干预措施: Anifrolumab SC injection (300mg) (Drug)
Anifrolumab 300 mg IV infusion
300 mg single dose anifrolumab delivered as an IV infusion over 30 minutes
干预措施: Anifrolumab IV infusion (300mg) (Drug)
Anifrolumab 600 mg SC infusion
600 mg single dose anifrolumab or placebo delivered as 4 mL SC by infusion pump
干预措施: Anifrolumab SC infusion (600mg) (Drug)
Placebo 300 mg IV infusion
300 mg single dose placebo delivered as an IV infusion over 30 minutes
干预措施: Anifrolumab placebo IV infusion (300mg) (Drug)
Placebo 600mg SC infusion
600 mg single dose placebo delivered as 4 mL SC by infusion pump
干预措施: Anifrolumab placebo SC infusion (600mg) (Drug)
结局指标
主要结局
Pharmacokinetics: Observed Maximum Serum Concentration (Cmax) Following Single Dose of Anifrolumab.
时间窗: On Day 1 pre-dose and at 5 minutes (IV cohort only), 24 and 48 hours post-dose and at each follow-up visit, up to 85 days
To evaluate Cmax of anifrolumab after single administration of two doses subcutaneously and one dose intravenously. Up to 13 blood samples were collected in total.
Pharmacokinetics: Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Following Single Dose of Anifrolumab
时间窗: On Day 1 pre-dose and at 5 minutes (IV cohort only), 24 and 48 hours post-dose and at each follow-up visit, up to 85 days
To evaluate AUC(0-t) of anifrolumab after single administration of two doses subcutaneously and one dose intravenously Up to 13 blood samples were collected in total.
Pharmacokinetics: Area Under Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) Following Single Dose of Anifrolumab
时间窗: On Day 1 pre-dose and at 5 minutes (IV cohort only), 24 and 48 hours post-dose and at each follow-up visit, up to 85 days
To evaluate AUC of anifrolumab after single administration of two doses subcutaneously and one dose intravenously. Up to 13 blood samples were collected in total.
Safety: Number of Participants With Adverse Events (AEs)
时间窗: From screening to final follow-up visit, up to 16 weeks
To assess the safety and tolerability of single doses of anifrolumab
Safety: Summary of Local Injection Site Pain (SC Cohorts) Assessed in Participants
时间窗: Immediately after dosing, at 10, 20 minutes and 1 hour after injection
Local injection site pain was assessed using a 100 mm participant rated Visual Analog Scale (VAS 0mm - 100mm ungraduated scale, where 0 = "no pain" to 100 = "worst imaginable pain"). This assessment was taken for only those participants in subcutaneously dosed treatment groups; 600 mg SC and 300 mg SC, anifrolumab and placebo. For the 300 mg SC anifrolumab and 300 mg SC placebo groups which received two simultaneous injections, the average VAS score (0mm-100mm) of the two injection sites were reported.
Safety: Summary of Local Injection Site Pruritus (SC Cohorts) Assessed in Participants
时间窗: Immediately after dosing, at 10, 20 minutes and 1 hour after injection
Local injection site pruritus was assessed using a 100 mm participant rated Visual Analog Scale (VAS 0mm - 100mm ungraduated scale, where 0 = "no itching" to 100 = "worst imaginable itching"). This assessment was taken for only those participants in subcutaneously dosed treatment groups; 600 mg SC and 300 mg SC, anifrolumab and placebo. For the 300 mg SC anifrolumab and 300 mg SC placebo groups which received two simultaneous injections, the average VAS score (0mm-100mm) of the two injection sites were reported.
Safety: Summary of Erythema Injection Site Reaction (SC Cohorts) Assessed in Participants
时间窗: Immediately after dosing, at 10, 20 minutes and 1 hour after injection
Erythema was measured as the largest diameter across the needle site on the skin in millimetres (mm). This assessment was taken for only those participants in subcutaneously dosed treatment groups; 600 mg SC and 300 mg SC, anifrolumab and placebo. For the 300 mg SC anifrolumab and 300 mg SC placebo groups which received two simultaneous injections, the average of the two injection site diameters (mm) were reported.
Safety: Summary of the Induration Injection Site Reaction (SC Cohorts) Assessed in Participants
时间窗: Immediately after dosing, at 10, 20 minutes and 1 hour after injection
Induration was measured as the largest diameter across the needle site on the skin in millimetres (mm). This assessment was taken for only those participants in subcutaneously dosed treatment groups; 600 mg SC and 300 mg SC, anifrolumab and placebo. For the 300 mg SC anifrolumab and 300 mg SC placebo groups which received two simultaneous injections, the average of the two injection site diameters (mm) were reported.
次要结局
- Evaluation of Immunogenicity of Anifrolumab IV Infusions and SC Injections by the Measurement of Anti-drug Antibody (ADA).(Pre-dose and at Days 5 and Day 29, up to 85 days)