NCT01932242已完成1 期
A Double-Blind, Randomized, Placebo-Controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of Repeat Administration of Intravenous ETI-204 in Adult Volunteers
Elusys Therapeutics4 个研究点 分布在 1 个国家目标入组 70 人开始时间: 2013年7月23日最近更新:
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 70
- 试验地点
- 4
- 主要终点
- Number of Participants Who Experienced Adverse Events
研究概览
简要总结
To evaluate the safety, tolerability, pharmacokinetics and immunogenicity of repeat administration (two doses) of intravenous (IV) ETI-204.
详细描述
A double-blind, randomized, placebo-controlled, study in 70 healthy adult subjects. The total duration of the study for each subject will be approximately 220 days divided as follows:
- Screening: Days -28 to -2
- Three In-Unit Stays: Days -1 to 2; Days 13 to 15; and Days 119 to 121
- Out-of-Unit Visit Days: Day 8 (±2 days); Day 28 (±3 days); Day 43 (±3 days); Day 71 (±3 days); Day 85 (±3 days); Day 128 (±3 days); Day 134 (±3 days); Day 149 (±3 days); and Day 163 (±3 days)
- Final Visit: Day 191 (±3 days)
Subjects will be randomized in a 1:1 ratio to one of the following two treatment sequences:
- Sequence A: ETI-204 on Days 1 and 14 and placebo on Day 120
- Sequence B: ETI-204 on Days 1 and 120 and placebo on Day 14
Subjects who qualify for entry into the study following completion of the Screening visit will arrive at the clinical research unit (CRU) on Day -1. The next day, Day 1, qualified subjects will be randomized and will receive a single IV dose of ETI-204. Subjects will be pretreated with 50 mg oral diphenhydramine approximately 30 minutes prior to the start of the study drug infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Study drug will be prepared by an unblinded pharmacist not involved with the conduct of the study. The pharmacist will assign the correct study drug (16 mg/kg ETI-204 or placebo) to each subject according to the randomization scheme.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Females or males ≥ 18 years of age
- •All females, regardless of childbearing potential, must have a negative serum beta human chorionic gonadotropin (β-hCG) pregnancy test at Screening and Day -1
- •Females of childbearing potential (i.e., not postmenopausal or surgically sterile) must agree to practice abstinence or to use a medically accepted method of contraception from the time of Screening through 30 days after the final study visit. Acceptable methods of contraception include diaphragm with spermicide; sponge with spermicide; condom with spermicide; or intrauterine device with condom or spermicide. The following contraceptive methods are acceptable only when used with a condom and spermicide: birth control pills, birth control patches, vaginal ring, hormone under the skin, or hormone injections
- •Postmenopausal females, defined as females who have had amenorrhea for at least 12 months either naturally or following cessation of all exogenous hormonal treatments, and have a follicle-stimulating hormone (FSH) level of > 40 mIU/mL at Screening
- •Females who have undergone surgical sterilization, including hysterectomy, bilateral oophorectomy, bilateral salpingectomy, tubal ligation, or tubal essure
- •Males must agree to practice abstinence or use a condom with spermicide and refrain from sperm donation during the study and for 30 days after the final study visit
- •Provide written informed consent
- •Willing to comply with study restrictions
排除标准
- •Pregnant or lactating woman
- •Clinically significant comorbidity that would interfere with completion of the study procedures or objectives or compromise the subject's safety
- •Seated systolic blood pressure (BP) ≥ 150 mmHg or ≤ 90 mmHg or diastolic BP ≥ 95 mmHg
- •Use of H1 receptor antagonists (i.e. antihistamines) within 5 days prior to Day 1
- •Evidence of drug or alcohol abuse as determined by the Investigator within 6 months of Day 1
- •Positive test result for drugs of abuse (with the exception of medically prescribed drugs) at Screening or on Day -1
- •Positive test for alcohol at Screening; exclusion is at the Investigator's discretion; subjects who test positive for alcohol at Day -1 are excluded from the study
- •Treatment with an investigational agent within 30 days or five half-lives of the investigational agent at Day 1 (whichever is longer)
- •Congenital or acquired immunodeficiency syndrome
- •Prior solid organ or bone marrow transplant
- •Positive test for Hepatitis B (surface antigen), Hepatitis C, or human immunodeficiency virus (HIV) at Screening
- •History of prior treatment for anthrax exposure or prior anthrax infection
- •Prior immunization with any approved or investigational anthrax vaccine or prior treatment with an approved or investigational anthrax treatment (i.e., ETI-204, raxibacumab, or anthrax immune globulin)
- •Military personnel deployed in 1990 or after, unless the subject can provide documentation demonstrating they have not previously received any approved or investigational anthrax vaccine
- •Use of systemic steroids, immunosuppressive agents, anticoagulants, or anti-arrhythmics within 1 year prior to Day
- •A single short course (i.e., less than 14 days) of systemic steroid therapy is allowed provided it concluded more than 6 months prior to Day 1
- •Donation or loss of > 500 mL of blood within 30 days or plasma within 7 days of Day 1
- •Prior stroke, epilepsy, relapsing or degenerative central nervous system disease, or relapsing or degenerative ocular disease
- •Myocardial infarction or acute coronary syndrome in the past 5 years, active angina pectoris, or heart failure (New York Heart Association scale > 1)
- •History of chronic liver disease
- •Calculated creatinine clearance (CrCl) of < 30 mL/min using the Cockcroft-Gault equation (see Section 5.1)
- •Any clinically significant abnormality, in the Investigator's opinion, on electrocardiogram (ECG) or clinical laboratory tests (hematology, clinical chemistry, or urinalysis) at Screening; Out of range results may be repeated to confirm.
- •History of allergic or hypersensitivity reactions to other therapeutic antibodies or immunoglobulins
- •History of any malignant neoplasm within the last 5 years, with the exception of adequately treated, localized or in situ non-melanoma carcinoma of the skin (e.g., basal cell carcinoma) or the cervix
- •Subjects who, in the opinion of the Investigator, are not suitable candidates for enrollment or who may not comply with the requirements of the study
研究组 & 干预措施
Sequence A
Experimental
An intravenous dose of 16 mg/kg ETI-204 infused over 90 minutes on Days 1 and 14 and an intravenous dose of ETI-204-Placebo infused over 90 minutes on Day 120.
干预措施: Placebo (Other)
Sequence B
Experimental
An intravenous dose of 16 mg/kg ETI-204 infused over 90 minutes on Days 1 and 120 and an intravenous dose of ETI-204-Placebo infused over 90 minutes on Day 14.
干预措施: Placebo (Other)
Sequence B
Experimental
An intravenous dose of 16 mg/kg ETI-204 infused over 90 minutes on Days 1 and 120 and an intravenous dose of ETI-204-Placebo infused over 90 minutes on Day 14.
干预措施: ETI-204 (Biological)
Sequence A
Experimental
An intravenous dose of 16 mg/kg ETI-204 infused over 90 minutes on Days 1 and 14 and an intravenous dose of ETI-204-Placebo infused over 90 minutes on Day 120.
干预措施: ETI-204 (Biological)
结局指标
主要结局
Number of Participants Who Experienced Adverse Events
时间窗: Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm.
Safety was assessed for all subjects in the safety population by collecting and monitoring vital signs, laboratory tests, ECGs, physical examinations, skin assessments, infusion site assessments and adverse events.
次要结局
- Maximum Observed Plasma Concentration of ETI-204 (Cmax) After a Dose of 16 mg/kg on Day 120 (Sequence B)(On Day 120 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.)
- Volume of Distribution (Vd) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B) or Two Doses on Days 1 and 14 (Sequence A)(On Days 1 and 14 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.)
- Volume of Distribution (Vd) After a Dose of 16 mg/kg ETI-204 on Day 120 (Sequence B)(On Day 120 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.)
- Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax) After a Dose of 16 mg/kg on Day 1(Sequence B) or Two Doses on Days 1 and 14 (Sequence A)(On Days 1 and 14 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.)
- Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax) After a Dose of 16 mg/kg on Day 120 (Sequence B)(On Day 120 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.)
- Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-last) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B) or Two Doses on Days 1 and 14 (Sequence A)(On Days 1 and 14 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.)
- Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-last) After a Dose of 16 mg/kg ETI-204 on Day 120 (Sequence B)(On Day 120 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.)
- Area Under the Concentration-Time Curve From Time Zero to 120 Days (AUC0-120days) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B)(On Day 1 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.)
- Terminal Half-life (t1/2) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B) or Two Doses on Days 1 and 14 (Sequence A)(On Days 1 and 14 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.)
- Maximum Observed Plasma Concentration of ETI-204 (Cmax) After a Dose of 16 mg/kg on Day 1(Sequence B) or Two Doses on Days 1 and 14 (Sequence A)(On Days 1 and 14 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.)
- Area Under the Concentration-Time Curve From Time Zero to 191 Days (AUC0-191days) After a Dose of 16 mg/kg ETI-204 on Days 1 and 14 (Sequence A)(On Days 1 and 14 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.)
- Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B) or Two Doses on Days 1 and 14 (Sequence A)(On Days 1 and 14 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.)
- Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) After a Dose of 16 mg/kg ETI-204 on Day 120 (Sequence B)(On Day 120 prepose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.)
- Terminal Half-life (t1/2) After a Dose of 16 mg/kg ETI-204 on Day 120 (Sequence B)(On Day 120 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.)
- Systemic Clearance (CL) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B) or Two Doses on Days 1 and 14 (Sequence A)(On Days 1 and 14 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.)
- Number of Participants With Anti-ETI-204 Antibodies(On Days 1,14, and 120 predose and on Days 8, 43, 85, 128, 163, and 191)
- Systemic Clearance (CL) After a Dose of 16 mg/kg ETI-204 on Day 120 (Sequence B)(On Day 120 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.)
- Volume of Distribution at Steady State (Vdss) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B)(On Day 1 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.)
- Volume of Distribution at Steady State (Vdss) After a Dose of 16 mg/kg ETI-204 on Day 120 (Sequence B)(On Day 120 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.)
研究者
研究点 (4)
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