A Phase 1, Randomized, Double-blind, Placebo-controlled Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Subcutaneous ANX009 in Normal Healthy Volunteers (NHV)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Safety: Number of Participants Who Experienced Treatment-Emergent Adverse Events
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmakokinetics and pharmacodynamics of single and repeated doses of ANX009
详细描述
In this first in human, phase 1, randomized, double-blind, placebo-controlled study, single and multiple ascending doses of ANX009 or placebo will be administered to 48 healthy subjects.
Single Ascending Dose (SAD): Each SAD subject will participate for approximately 4 weeks (3 nights in-clinic confinement).
Multiple Ascending Dose: Each MAD subject will participate for approximately 6 weeks (17 nights in-clinic confinement).
All subjects will be contacted (in clinic visit or phone call) 6 months after study completion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and non-pregnant, non-lactating female volunteers ≥18 to 59 years of age.
- •Females must be postmenopausal, surgically sterilized or willing and able to use highly effective methods of contraception from screening through the final study visit.
- •Males with a partner of childbearing potential must agree to use contraception from Screening through the final study visit.
- •Documented history within 5 years of screening of previous vaccination against encapsulated bacterial pathogens (MAD cohorts only).
- •Complete the full sequence of protocol-related doses, procedures and evaluations.
- •No alcohol and drugs of abuse at screening and baseline or through study completion.
- •Discontinue use of nutritional supplements and prescription and over-the-counter medications (vitamins are allowed).
- •No new tattoos/piercings or elective surgery from screening through the End of Study visit
- •Ability to understand and provide written informed consent.
排除标准
- •Subjects must not meet any of the following criteria:
- •Clinically significant, ongoing illness or medical condition that would jeopardize the safety of the subject, limit participation, or compromise the interpretation of the safety data derived from the subject.
- •Clinically significant findings on the screening or Baseline ECG or physical examination.
- •Clinically significant abnormalities on screening or Baseline laboratory assessments.
- •An ANA titer ≥ 1:
- •History of any autoimmune disease.
- •History of meningitis or septicemia.
- •Clinically significant infection that required medical intervention (not including antibiotic prophylaxis) within 1 month prior to study drug dosing.
- •Known genetic deficiencies of the complement cascade system or immunodeficiency.
- •Treatment with an investigational therapeutic agent within 30 days prior to study drug dosing.
- •Use of immunosuppressants or corticosteroids within 30 days prior to study drug dosing.
- •Active alcohol abuse, drug abuse or substance abuse.
- •Hypersensitivity to any of the excipients in the ANX009 drug product or active substance.
- •History of previous sensitivities or allergic or anaphylactic reactions to previous medication injections.
- •Positive for HIV Ab, Hepatitis C Ab or Hepatitis B surface antigen (HBsAg) at screening.
- •Body weight less than 50 kg or greater than 125 kg.
- •BMI less than 18 or greater than 30 (Asians greater than 27).
- •Current smoker defined as any occasional or daily smoking of tobacco products
研究组 & 干预措施
ANX009, Single Ascending Doses
Single dose of ANX009 with a 7-day follow-up before escalation to the next dose level.
干预措施: ANX009 (Drug)
Placebo, Single Ascending Doses
Single doses of matching placebo
干预措施: Placebo (Drug)
ANX009, Multiple Ascending Doses
ANX009 once daily on Days 1-14
干预措施: ANX009 (Drug)
Placebo, Multiple doses
Matching placebo once daily on Days 1-14
干预措施: Placebo (Drug)
结局指标
主要结局
Safety: Number of Participants Who Experienced Treatment-Emergent Adverse Events
时间窗: [Time Frame: Up to Day 29 for SAD; up to Day 43 for MAD]
Incidence and severity of treatment-emergent adverse events (AEs). AEs will be coded using MedDRA and severity of AEs will be graded using National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE).
次要结局
- Pharmacodynamics: Total Amount of Complement Protein in Blood (CH50)(Up to Week 6)
- Pharmacodynamics: Amount of C1 in Blood (C1q)(Up to Week 6)
- Pharmacokinetic: Maximum Observed Serum Concentration (Cmax) of ANX009(Pre-dose, immediately after dose, and 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose on Day 1 (SAD and MAD) and 36, 48, and 72 hours post-dose Day 1 (SAD))
- Pharmacokinetic: Time to Maximum Observed Serum Concentration (Tmax) of ANX009(Pre-dose, immediately after dose, and 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose on Day 1 (SAD and MAD) and 36, 48, and 72 hours post-dose Day 1 (SAD))
- Pharmacokinetic: Area Under the ANX009 Serum Concentration-Time Curve to Last Sample (AUC 0-t) and extrapolated through infinity (AUC 0-inf)(Pre-dose, immediately after dose, and 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose on Day 1 (SAD and MAD) and 36, 48, and 72 hours post-dose Day 1 (SAD))
- Pharmacokinetic: Terminal Half-Life (t1/2) of ANX009(Pre-dose, immediately after dose, and 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose on Day 1 (SAD and MAD) and 36, 48, and 72 hours post-dose Day 1 (SAD))