Immunogenicity and Safety of 2 Doses of Avian Influenza A (H5N1) Vaccine Administered 3 vs. 8 Weeks Apart - A Multi-Center Non-Inferiority Placebo-Controlled Observer-Blinded Phase 2 Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 312
- 试验地点
- 4
- 主要终点
- Percentages of participants with seroprotection against the H5N1 2.3.4.4b clade vaccine given 3 vs. 8 weeks apart
研究概览
简要总结
Given the recent circulation of avian influenza A(H5N1) clade 2.3.4.4b strains in birds and mammals in North America, Canada procured a supply of Arepanrix™ H5N1 for potential use in persons at high risk of highly pathogenic avian influenza exposure.
This vaccine received regulatory approval in 2013, to be given in two doses at least 3 weeks apart. There is limited data on the effect of various intervals between the two doses on immunogenicity and tolerability. In this study two intervals between doses will be compared (3 vs. 8 weeks apart).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Individuals in stable health (defined as no new onset or exacerbation of pre-existing chronic disease three months prior to vaccination) 18-59 years of age.
- •Able to comply with the trial procedures.
- •Informed consent signed prior to trial-specific procedures.
- •If a person is at risk of becoming pregnant, has practiced adequate contraception for 28 days prior to visit 1, and has a negative pregnancy test on the day of vaccination and has agreed to continue adequate contraception until 60 days after the final vaccination.
- •Risk of pregnancy is defined as any cis woman and/or gender divergent individual assigned female at birth or with reproductive capacity who is sexually active with individuals with sperm-producing capabilities.
- •Individual who are post-menopausal or permanently sterile (hysterectomy, bilateral salpingectomy) are not considered at risk of pregnancy. A post-menopausal state is defined as a no menses for 12 months.
- •Effective contraception methods are:
- •Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
- •Intravaginal
- •Transdermal
- •Progestogen-only hormonal contraception associated with inhibition of ovulation:
- •Injectable
- •Implantable
- •Intra-uterine device (IUD) with or without hormonal release.
- •Vasectomised partner, provided that this partner is your sole sexual partner and that the vasectomised partner has received a medical assessment of the surgical success.
- •Credible self-reported history of heterosexual abstinence prior to and for at least 28 days after the vaccine.
- •Effective contraception methods are:
- •Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
- •Intravaginal
- •Transdermal
- •Progestogen-only hormonal contraception associated with inhibition of ovulation:
- •Injectable
- •Implantable
- •Intra-uterine device (IUD) with or without hormonal release.
- •Vasectomised partner, provided that this partner is your sole sexual partner and that the vasectomised partner has received a medical assessment of the surgical success.
- •Credible self-reported history of heterosexual abstinence prior to and for at least 28 days after the vaccine.
排除标准
- •Any of the following:
- •Receipt of avian influenza A(H5N1) vaccine anytime.
- •Positive pregnancy test prior to vaccination, or breastfeeding.
- •Receipt of immunoglobulins and/or any blood products within 3 months preceding the first dose of study vaccine and for one month after the last dose of study vaccine (except Rho D).
- •Bleeding disorder or history of significant bleeding following IM injections or venipuncture.
- •Any confirmed or suspected immunosuppressive or immunodeficient state; asplenia, or immunosuppressant medication within the past 6 months except short term oral steroids (≤14 days duration) or topical steroids.
- •A significant acute disease or temperature ≥38 Co within 24 hours prior to vaccination (temporary exclusion criteria, participants can return for evaluation to be randomized/ vaccinated 72 hours after symptoms resolve).
- •Unstable chronic medical condition requiring ongoing follow-up and monitoring by a physician as determined by the investigator.
- •History of anaphylaxis or allergy to any of the constituents or trace residues of the study vaccine, including egg protein.
- •Receipt of non-study vaccine(s) 2 weeks prior to the study vaccine or planned 2 weeks after administration of the study vaccine.
研究组 & 干预措施
Group 1: H5N1 vaccines administered 3 weeks apart
Two doses of the H5N1 vaccine administered 3 weeks apart.
Normal saline will be administered as a placebo at week 8.
干预措施: H5N1 vaccine (Arepanrix) (Biological)
Group 1: H5N1 vaccines administered 3 weeks apart
Two doses of the H5N1 vaccine administered 3 weeks apart.
Normal saline will be administered as a placebo at week 8.
干预措施: Saline (as a placebo) (Other)
Group 2: H5N1 vaccines administered 8 weeks apart
Two doses of the H5N1 vaccine administered 8 weeks apart
Normal saline will be administered as a placebo at week 3.
干预措施: H5N1 vaccine (Arepanrix) (Biological)
Group 2: H5N1 vaccines administered 8 weeks apart
Two doses of the H5N1 vaccine administered 8 weeks apart
Normal saline will be administered as a placebo at week 3.
干预措施: Saline (as a placebo) (Other)
结局指标
主要结局
Percentages of participants with seroprotection against the H5N1 2.3.4.4b clade vaccine given 3 vs. 8 weeks apart
时间窗: 28 days post-administration of 2 doses of avian influenza A (H5N1 (Approximately week 12).
Percentages of participants with seroprotection against the H5N1 2.3.4.4b clade 28 days following administration of 2 doses of avian influenza A(H5N1) vaccine given 3 vs. 8 weeks apart based on serologic outcomes at visit 4 (approximately week 12). Seroprotection is defined as the proportion of subjects who were either seronegative prior to vaccination and have a protective post-vaccination HI titre of ≥ 1:40 or who were seropositive prior to vaccination and have at least a 4-fold increase in HI titre post-vaccination.
次要结局
- Immunogenicity - Percentages of participants with seroprotection, seroconversion and the geometric mean fold rise against the H5N1 2.3.4.4b clade(at baseline, at 3 weeks, at 8 weeks, 12 weeks, 26 weeks and through study completion (average of 1 year).)
- Immunogenicity - Percentages of participants with seroprotection, seroconversion and the geometric mean fold rise against the H5N1 2.3.4.4b clade(6 and 12 months after the first dose of avian influenza A (H5N1) vaccine)
- Immunogenicity - Percentages of participants with seroconversion and the geometric mean fold rise against the H5N1 2.3.4.4b clade vaccine given 3 vs. 8 weeks apart.(28 days post-administration of 2 doses of avian influenza A (H5N1))
- Incidence of Grade 3 & 4 Adverse Events(Up to 12 months after the first dose of avian influenza A (H5N1) vaccine)
- Immunogenicity - GMT of HI against the H5N1 2.3.4.4b clade vaccine given 3 vs. 8 weeks apart.(28 days post-administration of 2 doses of avian influenza A (H5N1) vaccine)
研究者
Joanne Langley
Principal Investigator
Canadian Immunization Research Network