A Phase 1, Open Label, Ascending Dose Cohort Study of the Pharmacokinetics of Anti-Influenza Hyperimmune Intravenous Immunoglobulin in Healthy Subjects
Despite currently available antivirals, influenza causes significant morbidity and mortality, with 226,000 excess hospitalizations and 30,000-50,000 deaths each year in the United States alone, and more therapies are needed in the armamentarium of anti-influenza medications including humoral immunity-based agents.
This study will evaluate the pharmacokinetics of an anti-influenza hyperimmune intravenous immunoglobulin. Beginning with a low dose, subjects will receive anti-influenza intravenous immunoglobulin (FLU-IVIG) and evaluated on Study Days 0, 3, 7, 14, and 28. The safety and tolerability is evaluated using symptoms, clinical laboratory tests, and pharmacokinetics. Utilizing serum antibody responses as determined by hemagglutination inhibition (HAI) assays, the dose will be escalated as immunogenicity is established....
研究概览
详细说明
Despite currently available antivirals, influenza causes significant morbidity and mortality, with 226,000 excess hospitalizations and 30,000-50,000 deaths each year in the United States alone, and more therapies are needed in the armamentarium of anti-influenza medications including humoral immunity-based agents.
This study will evaluate the pharmacokinetics of an anti-influenza hyperimmune intravenous immunoglobulin. Beginning with a low dose, subjects will receive anti-influenza intravenous immunoglobulin (FLU-IVIG) and evaluated on Study Days 0, 3, 7, 14, and 28. The safety and tolerability is evaluated using symptoms, clinical laboratory tests, and pharmacokinetics. Utilizing serum antibody responses as determined by hemagglutination inhibition (HAI) assays, the dose will be escalated as immunogenicity is established.
研究类型
阶段
- 阶段1
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
INCLUSION CRITERIA:
- Age greater than or equal to 18 years and less than or equal to 50 years
- Weight less than or equal to 100 kg
- Patients must be willing to forgo the seasonal influenza vaccine for 28 days, and the MMR and varicella vaccines for 3 months post infusion of the study drug
- Females who are able to become pregnant (i.e., are not postmenopausal, have not undergone surgical sterilization, and are sexually active with men) must agree to use at least 1 effective form of contraception from the date of the subject s signing of the informed consent form through 28 days after the dose of the study drug
EXCLUSION CRIATERIA:
- Any chronic medical problem that requires daily oral medications (except Tylenol, oral contraceptives, vitamins, and seasonal allergy medications), or other medical history that in the opinion of the investigator significantly increases the risk associated with IVIG
- Women who are breast-feeding
- Positive urine or serum pregnancy test
- Known sensitivity to IVIG
- IgA < 7 mg/dL
- Influenza HAI H1N1 > 1:20
- Receipt of any vaccination within 30 days prior to study drug administration
- Pre-existing condition that is associated with an increased risk of thrombosis such as cryoglobulinemia, hyper-triglyceridemia, or monoclonal gammopathies
- Estimated glomerular filtration rate (GFR) < 60 mL/min at screening, calculated using the MDRD formula
- Medical conditions for which receipt of up to 750 mL volume may be dangerous to the patient (e.g., decompensated congestive heart failure)
Abnormal chemistry panel
-Defined as any clinically significant baseline Grade 1 or greater toxicity, or any Grade 3 or greater toxicity (regardless of clinical significance) by the toxicity table
--Evaluating only total CO2 (bicarbonate), creatinine, alkaline phosphatase, ALT, AST, total bilirubin, and estimated GFR by the MDRD equation
Abnormal complete blood count (CBC)
-Defined as any clinically significant baseline Grade 1 or greater toxicity, or any Grade 3 or greater toxicity (regardless of clinical significance) by the toxicity table
--Evaluating only the WBC, hemoglobin, hematocrit, and platelets
- Positive serology for Hepatitis B surface antigen
- Positive serology for Hepatitis C
- Positive serology for HIV-1
- Prior treatment with any investigational drug therapy within 5 half-lives or 30 days, whichever is longer, prior to study drug administration (i.e., Day 0)
- Receipt of blood products from 30 days prior to study drug administration (i.e., Day 0) through 28 days after the dose of the study drug
- Presence of any pre-existing illness that, in the opinion of the investigator, would place the patient at an unreasonably increased risk through participation in this study
- Patients who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:非随机化
- 介入模型:阶乘赋值
- 屏蔽:无(打开标签)
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
|---|---|
|
HAI titer levels predose, at 1 hr post-infusion, and on Days 3, 7, 14 and 28
大体时间:6 months
|
6 months
|
次要结果测量
结果测量 |
大体时间 |
|---|---|
|
Type and frequency of adverse events experienced by subjects receiving anti-influenza IVIG by intravenous administration at escalating dose-levels
大体时间:6 months
|
6 months
|
合作者和调查者
出版物和有用的链接
一般刊物
- Kumar A, Zarychanski R, Pinto R, Cook DJ, Marshall J, Lacroix J, Stelfox T, Bagshaw S, Choong K, Lamontagne F, Turgeon AF, Lapinsky S, Ahern SP, Smith O, Siddiqui F, Jouvet P, Khwaja K, McIntyre L, Menon K, Hutchison J, Hornstein D, Joffe A, Lauzier F, Singh J, Karachi T, Wiebe K, Olafson K, Ramsey C, Sharma S, Dodek P, Meade M, Hall R, Fowler RA; Canadian Critical Care Trials Group H1N1 Collaborative. Critically ill patients with 2009 influenza A(H1N1) infection in Canada. JAMA. 2009 Nov 4;302(17):1872-9. doi: 10.1001/jama.2009.1496. Epub 2009 Oct 12.
- Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, Hernandez M, Quinones-Falconi F, Bautista E, Ramirez-Venegas A, Rojas-Serrano J, Ormsby CE, Corrales A, Higuera A, Mondragon E, Cordova-Villalobos JA; INER Working Group on Influenza. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med. 2009 Aug 13;361(7):680-9. doi: 10.1056/NEJMoa0904252. Epub 2009 Jun 29.
- Dwyer DE; INSIGHT Influenza Study Group. Surveillance of illness associated with pandemic (H1N1) 2009 virus infection among adults using a global clinical site network approach: the INSIGHT FLU 002 and FLU 003 studies. Vaccine. 2011 Jul 22;29 Suppl 2(0 2):B56-62. doi: 10.1016/j.vaccine.2011.04.105.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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