A Phase I Randomized, Observer-blind, Controlled, Dose Escalation Trial of the Safety and Tolerability of a Single Intramuscular Dose of a PAL Adjuvant (FB-631) Co-administered With Seasonal TIV (2013-2014) in Healthy Adults.
试验速览
- 阶段
- 1 期
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- Safety
研究概览
简要总结
This is a phase 1, research study is looking at the safety and acceptability of a new vaccine adjuvant (immune booster) called PAL when combined with the seasonal flu vaccine (Fluviral) to test the safety and effectiveness of new vaccines and medications on healthy volunteers.
The study will enroll approximately 48 healthy adult participants, and occur over 3 years. In the first six months/180 days of the study participants will have visits to the study site during which safety and immunogenicity outcomes will be measured. From Day 181 to Year 3, participants will be contacted by telephone or email to collect information on any adverse events.
详细描述
This is a phase 1, dose-ranging, randomized (5:1), observer-blind, controlled study of the safety and immune response to intramuscular injection of PapMV (Papaya Mosaic Virus) rVLP (Recombinant Virus-Like Particles) which is PAL adjuvant, or "PAL" combined with Trivalent Influenza Vaccines (TIV) at one of four dose levels of PAL, combined with one of two dose levels of TIV, or active control (TIV). The study will enroll approximately 48 healthy adult participants, and occur over 3 years. In the first six months/180 days (Epoch 1) of the study participants will have visits to the study site during which safety and immunogenicity outcomes will be measured. In Epoch 2 (Day 181 to Year 3) participants will be contacted by telephone or email to collect unsolicited adverse events.
This is a controlled clinical trial. The control group will receive the standard dose of TIV, 0.5 mL, which consists of 15 μg haemagglutinin (HA) of each influenza strain recommended by the World Health Organization (WHO) for the 2013-2014 influenza season in the northern hemisphere. An active control is used so that the attributable risk of adverse events can be estimated, and so that outcome measures can be assessed in a blinded fashion. Only adults in stable health will be eligible in order to minimize participant risk. Only non-pregnant females of childbearing age are eligible, and they must agree to continue adequate contraception for 180 days after injection. Study holding rules and a safety evaluation by a Safety Review Committee (SRC) will be in place. The study will follow a staggered dose-escalation design, with each of four steps introducing a new dose of the adjuvant (30, 60, 120 and 240 μg respectively).
The first dose level of PAL adjuvant FB-631 is 0.5 X 60 µg (i.e., 30 µg), which is half the dose that was found to be most immunogenic in animal studies. The adjuvant is co-administered with 0.25 mL of TIV, which is half the dose of TIV that is routinely administered to adults (i.e. 7.5 μg of each of the three influenza subtypes contained in the vaccine). The next dose level is 60µg of FB-631 combined with 0.25 mL TIV. The third dose level is 120 μg of FB-631 with 0.25 mL TIV. In the fourth and final step the dose of adjuvant is 240 μg of PAL adjuvant combined with 0.25 mL TIV (8 participants) or 0.125 mL TIV (i.e. 3.75 μg HA of each influenza subtype contained in the vaccine) (8 participants).
Any safety signal observed in the study will lead to a hold until the decision of Safety Review Committee to continue, modify or suspend the conduct of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Good general health status, as determined by history and physical examination no greater than 30 days prior to administration of the first test article.
- •Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of Diary Cards, return for follow-up visits).
- •If female of child-bearing potential and heterosexually active, has practiced adequate contraception for 30 days prior to injection and has a negative pregnancy test on the day of injection and has agreed to continue adequate contraception until 180 days after injection. (Please refer to the glossary for the definition of child-bearing potential and adequate contraception).
排除标准
- •Use of any investigational or non-registered product (drug or vaccine) other than the study product within 28 days preceding the dose of study product, or planned use during the study period.
- •Planned administration/ administration of a vaccine/product not foreseen by the study protocol within the period starting 28 days before injection and ending 28 days after.
- •Planned administration/ administration of the seasonal influenza vaccine recommended by local public health authorities within the period starting 120 days before injection and ending 121 days after. (Note: enrolment should be completed 120 days before the annual seasonal influenza vaccine campaigns in October and December)
- •Administration of immunoglobulins and/or any blood products within the 3 months preceding the dose of study product or planned administration during the study period.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. (Laboratory testing for HIV, Hepatitis C and Hepatitis B will be performed during the screening visit).
- •Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drug within 6 months prior to the product dose
- •Family history of congenital or hereditary immunodeficiency.
- •History of or current autoimmune disease.
- •Known or suspected hypersensitivity to Fluviral, to thimerosal, or to any other ingredient in the formulation or component of the container.
- •Pregnant or lactating female.
- •Any hematological (hemoglobin level, white blood cell [WBC], and platelet count) and biochemical (alanine aminotransferase [ALT], aspartate aminotransferase [AST], blood urea nitrogen [BUN] and creatinine) abnormality as per local laboratory normal values considered clinically significant by the investigator.
- •Any acute or chronic, clinically significant disease, as determined by physical examination or laboratory screening tests.
- •Any other condition that the investigator judges may interfere with study procedures (e.g. drawing blood) or findings (e.g. immune response).
结局指标
主要结局
Safety
时间窗: 3 years
The occurrence of adverse events from injection to Day 1095 (36 months/three years, in all participants, in all groups:
次要结局
- Immunogenicity of TIV combined with PAL(6 months)
- Immune responses(6 months)
- Solicited and General Adverse Events(up to 6 months)
- Immunogenicity(6 months)
- Hematological laboratory values(up to 6 months)
- Induced immune responses(6 months)
- Unsolicited Adverse Events(3 years)