A Phase I/II Observer-blind, Randomized, Placebo-controlled, Multi-center Trial to Evaluate the Safety and Immunogenicity of Different Formulations of Monovalent Influenza A/Hong Kong/125/2017-like (H7N9) Virus Vaccine With AS03 Adjuvant System, Given as a Two-dose Series to Adults 18 to 64 Years of Age and 65 Years of Age and Older
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 833
- 试验地点
- 1
- 主要终点
- Number of Participants With Any Solicited Systemic Events
研究概览
简要总结
Study to evaluate the safety and immunogenicity of H7N9 antigen in combination with full or half doses of AS03 adjuvant system in healthy adults.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy participants as established by medical history and clinical examination before entering into the study.
- •A male or female ≥ 18 years of age at the time of first vaccination.
- •Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the diary cards and COVID-19 assessment card, return for follow-up visits, or return the diary cards and COVID-19 assessment card in a timely manner using the pre stamped envelope received at the site).
- •Written or witnessed/thumb printed informed consent obtained from the participant prior to performance of any study specific procedure.
- •Female participants of non-childbearing potential may be enrolled in the study. Non childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion hysterectomy, bilateral ovariectomy or post-menopause.
- •Female participants of childbearing potential may be enrolled in the study, if the participant:
- •has practiced adequate contraception for 1 month prior to vaccination, and
- •has a negative pregnancy test on the day of vaccination, and
- •has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.
排除标准
- •Current diagnosis or history of autoimmune disorder(s).
- •History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
- •Hypersensitivity to latex.
- •Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality that appears uncontrolled, as determined by history or physical examination.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
- •Recurrent history or uncontrolled neurological disorders or seizures.
- •History of Guillain-Barré syndrome.
- •Diagnosed with narcolepsy; or history of narcolepsy in a participant's parent, sibling or child.
- •Diagnosed with cancer, or treatment for cancer within 3 years.
- •Persons with a history of cancer who are disease-free without treatment for 3 years or more are eligible.
- •Persons with a history of histologically-confirmed basal cell carcinoma of the skin successfully treated with local excision only are accepted and are eligible, but other histologic types of skin cancer are exclusionary.
- •Women who are disease-free 3 years or more after treatment for breast cancer and receiving long-term prophylaxis (for example, with tamoxifen) are eligible.
- •Documented human immunodeficiency virus-positive participant.
- •Any clinically significant* hematological laboratory abnormality.
- •*The investigator should use his/her clinical judgement to decide which abnormalities are clinically significant.
- •Bedridden participants.
- •Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.
- •Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study vaccine/product during the period beginning 30 days before the first dose of study vaccine/product (Day -29 to Day 1), or planned use during the study period.
- •Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
- •Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the first dose of study vaccine/product or planned administration during the study period.
- •Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first vaccine/product dose. For corticosteroids, this will mean prednisone equivalent ≥ 20 mg/day. Inhaled and topical steroids are allowed.
- •Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational vaccine/product (drug or medical device).
- •Pregnant or lactating female.
- •Female planning to become pregnant or planning to discontinue contraceptive precautions within 2 months after completion of the vaccination series.
- •History of or current chronic alcohol consumption and/or drug abuse.
- •Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.
- •Any study personnel or immediate dependents, family, or household member.
研究组 & 干预措施
FLU-Q-PAN H7N9 Formulation 1_B Group
Healthy male and female participants who received two doses of FLU-Q-PAN H7N9 Formulation 1 vaccine and AS03B adjuvant. Participants received the first dose at Day 1 and the second dose at Day 22.
干预措施: FLU-Q-PAN H7N9 Formulation 1 (Biological)
FLU-Q-PAN H7N9 Formulation 1_B Group
Healthy male and female participants who received two doses of FLU-Q-PAN H7N9 Formulation 1 vaccine and AS03B adjuvant. Participants received the first dose at Day 1 and the second dose at Day 22.
干预措施: AS03B (Biological)
FLU-Q-PAN H7N9 Formulation 1_A Group
Healthy male and female participants who received two doses of FLU-Q-PAN H7N9 Formulation 1 vaccine and AS03A adjuvant. Participants received the first dose at Day 1 and the second dose at Day 22.
干预措施: FLU-Q-PAN H7N9 Formulation 1 (Biological)
FLU-Q-PAN H7N9 Formulation 1_A Group
Healthy male and female participants who received two doses of FLU-Q-PAN H7N9 Formulation 1 vaccine and AS03A adjuvant. Participants received the first dose at Day 1 and the second dose at Day 22.
干预措施: AS03A (Biological)
FLU-Q-PAN H7N9 Formulation 2_B Group
Healthy male and female participants who received two doses of FLU-Q-PAN H7N9 Formulation 2 vaccine and AS03B adjuvant. Participants received the first dose at Day 1 and the second dose at Day 22.
干预措施: FLU-Q-PAN H7N9 Formulation 2 (Biological)
FLU-Q-PAN H7N9 Formulation 2_B Group
Healthy male and female participants who received two doses of FLU-Q-PAN H7N9 Formulation 2 vaccine and AS03B adjuvant. Participants received the first dose at Day 1 and the second dose at Day 22.
干预措施: AS03B (Biological)
FLU-Q-PAN H7N9 Formulation 2_A Group
Healthy male and female participants who received two doses of FLU-Q-PAN H7N9 Formulation 2 vaccine and AS03A adjuvant. Participants received the first dose at Day 1 and the second dose at Day 22.
干预措施: FLU-Q-PAN H7N9 Formulation 2 (Biological)
FLU-Q-PAN H7N9 Formulation 2_A Group
Healthy male and female participants who received two doses of FLU-Q-PAN H7N9 Formulation 2 vaccine and AS03A adjuvant. Participants received the first dose at Day 1 and the second dose at Day 22.
干预措施: AS03A (Biological)
FLU-Q-PAN H7N9 Formulation 3_B Group
Healthy male and female participants who received two doses of FLU-Q-PAN H7N9 Formulation 3 vaccine and AS03B adjuvant. Participants received the first dose at Day 1 and the second dose at Day 22.
干预措施: FLU-Q-PAN H7N9 Formulation 3 (Biological)
FLU-Q-PAN H7N9 Formulation 3_B Group
Healthy male and female participants who received two doses of FLU-Q-PAN H7N9 Formulation 3 vaccine and AS03B adjuvant. Participants received the first dose at Day 1 and the second dose at Day 22.
干预措施: AS03B (Biological)
FLU-Q-PAN H7N9 Formulation 3_A Group
Healthy male and female participants who received two doses of FLU-Q-PAN H7N9 Formulation 3 vaccine and AS03A adjuvant. Participants received the first dose at Day 1 and the second dose at Day 22.
干预措施: FLU-Q-PAN H7N9 Formulation 3 (Biological)
FLU-Q-PAN H7N9 Formulation 3_A Group
Healthy male and female participants who received two doses of FLU-Q-PAN H7N9 Formulation 3 vaccine and AS03A adjuvant. Participants received the first dose at Day 1 and the second dose at Day 22.
干预措施: AS03A (Biological)
Placebo Group
Healthy male and female participants who received two doses of placebo, the first dose at Day 1 and the second dose at Day 22.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Any Solicited Systemic Events
时间窗: Within the 7-day follow-up period after Dose 2
Solicited systemic events assessed were fatigue, fever, headache, muscle ache all over body, joint pain, shivering, sweating and gastrointestinal symptoms (Nausea, vomiting, diarrhea and abdominal pain). Any = occurrence of symptom regardless of intensity grade. Fever was defined as temperature ≥38°C for oral route (preferred location for measuring temperature).
Number of Participants With Any and Related Potential Immune Mediated Diseases (pIMDs)
时间窗: From Day 1 up to Day 43
pIMDs are a subset of adverse events of special interest that included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have had an autoimmune etiology.
Number of Participants With Any SAEs
时间窗: From Day 1 up to Month 13
A SAE is any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization or result in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant. Abnormal pregnancy outcomes were also considered (e.g. spontaneous abortion, fatal death, stillbirth, congenital anomalies, ectopic pregnancy) or other situations where medical or scientific judgement was exercised in deciding whether reporting was appropriate.
Percentage of Seroconverted Participants for Anti-HI Antibodies Against Vaccine-homologous H7N9
时间窗: At Day 43
CBER criteria for seroconversion rate (SCR) for 18 to 64 years of age is shown if LL of the 99.17% CI for the SCR meets or exceeds 40%, and for ≥65 years of age, if the LL of the 99.17% CI for the SCR meets or exceeds 30%. Seroconversion is defined as a post-vaccination antibody titer ≥40 1/DIL in the serum of participants seronegative before vaccination (i.e. titer \< assay cut-off at Day 1). For seropositive participants (i.e. titer ≥ assay cut-off at Day 1), seroconversion requires a 4-fold rise in post-vaccination HI antibody titer (but at least a titer of 40 1/DIL). The percentage of participants was calculated with Clopper-Pearson exact two-sided 99.17% CIs. Note: The cut-off value for antibody titer was defined by the laboratory before the analysis.
Number of Participants With Any Solicited Administration Site Events
时间窗: Within the 7-day follow-up period after Dose 2
Solicited administered site events assessed were pain, redness and swelling. Any Pain = occurrence of symptom regardless of intensity grade. Any Redness or any Swelling symptom = any symptom having a surface diameter \>20 mm.
Number of Participants With Any and Related MAEs
时间窗: Within the 21-day follow-up period after Dose 2
MAEs were defined as adverse events with medically-attended visits that are not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason.
Number of Participants With Any and Related Medically Attended Adverse Events (MAEs)
时间窗: Within the 21-day follow-up period after Dose 1
MAEs were defined as adverse events with medically-attended visits that are not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason.
Number of Participants With Any pIMDs
时间窗: From Day 1 up to Month 13
pIMDs are a subset of adverse events of special interest that included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have had an autoimmune etiology.
Percentage of Seroprotected Participants for Anti-hemagglutination Inhibition (HI) Antibodies Against Vaccine-homologous H7N9
时间窗: At Day 43
Center for Biologics Evaluation and Research (CBER) criteria for seroprotection rate (SPR) for 18 to 64 years of age is shown if the Lower Limit (LL) of the 99.17% confidence interval (CI) for the SPR meets or exceeds 70%, and for greater than or equal to (≥) 65 years of age if the LL of the 99.17% CI for the SPR meets or exceeds 60%. SPR is defined as the percentage of participants with an HI antibody titer ≥40 1/dilution (DIL). The percentage of participants was calculated along with Clopper-Pearson exact two-sided 99.17% CIs.
Number of Participants With Any and Related Unsolicited Adverse Events
时间窗: Within the 21-day follow-up period after Dose 2
An unsolicited AE is an AE that was not solicited using a Participant Diary and that was spontaneously communicated by a participant who has signed the informed consent. Unsolicited AEs include serious and non-serious AEs. Potential unsolicited AEs may have been medically attended (i.e. symptoms or illnesses requiring a hospitalization, or emergency room visit, or visit to/by a health care provider). Unsolicited AEs that were not medically attended nor perceived as a concern by participant are collected during interview with the participants and by review of available medical records at the next visit. An unsolicited adverse event is any event reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Number of Participants With Any and Related Serious Adverse Events (SAEs)
时间窗: From Day 1 up to Day 43
A SAE is any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization or result in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant. Abnormal pregnancy outcomes were also considered (e.g. spontaneous abortion, fatal death, stillbirth, congenital anomalies, ectopic pregnancy) or other situations where medical or scientific judgement was exercised in deciding whether reporting was appropriate.
次要结局
- HI Antibody Titers Against Vaccine-homologous H7N9(At Day 1, Day 22 and Day 43)
- Percentage of Seroprotected Participants for HI Antibodies Against Vaccine-homologous H7N9(At Day 1 and Day 22)
- Percentage of Seroconverted Participants for HI Antibodies Against Vaccine-homologous H7N9(At Day 22)
- Vaccine Response Rate (VRR) of Anti-MN Antibodies Against Vaccine-homologous H7N9 for a Subset of Participants(At Day 22 and Day 43)
- Anti-microneutralization (MN) Antibody Titers Against Vaccine-homologous H7N9 for a Subset of Participants(At Day 1, Day 22 and Day 43)
- Percentage of Seropositive Participants for HI Antibodies Against Vaccine-homologous H7N9(At Day 1, Day 22 and Day 43)
- Mean Geometric Increase (MGI) of HI Antibody Titers Against Vaccine-homologous H7N9(At Day 22 (post-Dose 1/pre-vaccination) and Day 43 (post-Dose 2/pre-vaccination))
- Percentage of Seropositive Participants for Vaccine-homologous H7N9 MN Antibody Titers for a Subset of Participants(At Day 1, Day 22 and Day 43)