A Phase I, Randomized, Double-Blinded, Controlled, Dose Escalation Study to Evaluate the Safety and Immunogenicity of Recombinant Malaria Vaccines in Healthy Adults Aged 18-50 Years Old
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Immediate adverse events (AEs) within 30 minutes after each vaccination
研究概览
简要总结
This is a clinical trial in which healthy volunteers will receive one of three investigational malaria vaccines (LYB014, LYB017, and LYB027) administered in combination with the A02B adjuvant, or the A02B adjuvant alone as the control.
详细描述
A phase I, randomized, double-blinded, controlled, dose escalation study will be conducted to observe the safety and immunogenicity of LYB014, LYB017 and LYB027 in healthy adults aged 18-50 years old. This study includes six groups: Group 1, receiving a low dose of LYB014; Group 2, receiving a high dose of LYB014; Group 3, receiving a low dose of LYB017; Group 4, receiving a high dose of LYB017; Group 5, receiving a low dose of LYB027; and Group 6, receiving a high dose of LYB027. The adjuvant alone will serve as the control for all groups. The study progressed in a sequential manner, with Group 1 and Group 3 being enrolled and vaccinated first. Sentinels were employed for each group during the first dose vaccination. Each group included 3 sentinel participants who were dosed first. When the sentinel participants completed the laboratory tests 3 days after first vaccination, the principal investigator (PI) conducted the preliminary safety assessment including the laboratory tests results and confirmed safety, then remainder of cohort (ROC) in each group could be vaccinated.The Safety Review Committee (SRC) reviewed the safety data after all participants in Group 1 and Group 3 completed the 7 days visit after the first vaccination to allow the second vaccine dose in the Group 1 and Group 3, and the first vaccination in Group 2, Group 4 and Group 5. The SRC reviewed the safety data after all participants in Group 2, Group 4 and Group 5 completed the 7 days visit after the first vaccination to allow the second vaccine dose in Group 2, Group 4 and Group 5, and the first vaccination in Group 6. The SRC reviewed the safety data after all participants in Group 6 completed the 7 days visit after the first vaccination to allow the second vaccine dose in Group 6. SRC will review the 7-day safety data after second vaccination for participants in Group 1 and Group 3, and confirm the safety (meet no criteria for suspension/termination of the study) to allow third vaccination for Group 1 and Group 3. The same holds true for Group 2, Group 4 and Group 5, and Group 6.
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)
盲法说明
During the course of the study, both the participants and the investigators will all be unaware of which vaccine was administered.
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
- •1) Healthy males or females aged 18-50 years (inclusive) at the time of screening.
- •2) Written informed consent obtained from the participant before any assessment is performed.
- •3) Participants who the investigator believes that they can and will comply with the requirements of the protocol. (e.g., complete the diary cards, and complete follow-up visits).
- •4) Participants must have a Body Mass Index (BMI) between ≥18.0 and ≤35.0 kg/m2 at screening.
- •5) Female participants who are not pregnant or lactating. Female participants with childbearing potential and their partners should use highly effective, medically accepted double-barrier contraception, or persistent lifestyle abstinence and will not have pregnancy and fertility plan and refrain from donating ovum from at least 28 days prior to study vaccination/Day 1 until study completion.
- •A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
- •Highly effective double-barrier contraception is defined as use of a condom AND one of the following from at least 28 days prior to study vaccination/Day 1 until study completion: birth control pills (The Pill), depot or injectable birth control, intrauterine device (IUD), NuvaRing®, implantable contraception (e.g., Implanon).
- •Female participants who have had bilateral tubal ligation and are willing to use a condom when sexually active with the opposite sex.
- •Note: There is no contraception requirement for female participants with non-childbearing potential (WNCBP) and WNCBP participants' male partners must use a condom from study vaccination/Day 1 until study completion. Female participants who are in same-sex relationships should use a barrier form of contraception (e.g., diaphragm) from study vaccination/Day 1 until study completion.
- •6) Males participating in this study who are involved in heterosexual sexual activity with a female partner of childbearing potential must agree to use highly effective, medically accepted double-barrier contraception (as described above), or persistent lifestyle abstinence and refrain from donating sperm from at least 28 days prior to study vaccination until study completion.
- •Note: male participants who have undergone a vasectomy and are involved in heterosexual sexual activity with a female partner of childbearing potential are recommended to use double-barrier contraception. Male participants with WNCBP partners must use a condom only from study vaccination/Day 1 until study completion. Male Participants who are in same-sex relationships should use a barrier form of contraception (e.g., condom) from study vaccination/Day 1 until study completion.
排除标准
- •1) Tympanic temperature > 37.5°C at screening or prior to first vaccination. 2) Received a live attenuated vaccine within 28 days before first vaccination or received other vaccines within 14 days before first vaccination.
- •3) Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period.
- •4) Prior receipt of an investigational malaria vaccine or any other investigational vaccine likely to impact on interpretation of the trial data.
- •5) Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.
- •6) Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed).
- •7) Any acute disease or acute attack of chronic diseases or using antipyretic, analgesic or anti-allergic drugs (e.g., acetaminophen, ibuprofen, aspirin, loratadine, cetirizine, etc.) within 24 h prior to the first vaccination.
- •8) Allergies to any component of the investigational vaccine. 9) Any history of anaphylaxis in relation to vaccination. 10) History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ, the above two types of carcinomas must be fully resolved for at least 3 months before screening).
- •11) History of serious psychiatric or neurological condition likely to affect participation in the study (except history of childhood or febrile seizures; history of anxiety, depression, or attention-deficit/hyperactivity disorder (ADHD) that remains stable, with no required medication for the conditions for at least 6 months prior to screening, and no clinically significant worsening requiring intervention).
- •12) Congenital or acquired autoimmune disease. 13) Any other serious chronic illness requiring hospital specialist supervision.
- •14) A positive urine drug test (except positive cotinine results due to casual and social smoking) or alcohol breath test at screening or Day
- •15) Weekly cigarette consumption exceeding 5 cigarettes, and unwilling to completely abstain from smoking during their stay at the clinical site.
- •16) Positive test for hepatitis C virus (HCV), hepatitis B surface antigen (HbsAg), human immunodeficiency virus (HIV) at screening.
- •17) History of clinical malaria (any species). 18) Travel to a malaria endemic region during the study period or within 4 weeks prior to first vaccination.
- •19) Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis.
- •20) Have donated blood or plasma within 7 days prior to screening. 21) Any other significant disease, disorder or finding which may significantly increase the risk to the participant because of participation in the study, affect the ability of the participant to participate in the study or impair interpretation of the study data.
- •22) Other conditions that may impact the participant's safety or influence the assessment of vaccine response, as determined by the investigator.
研究组 & 干预措施
Low dose of LYB014
Young adults (18-59 years old) will receive three injections of low dose LYB014 at 28-day intervals.
干预措施: LYB014 low dose (Biological)
High dose of LYB014
Young adults (18-59 years old) will receive three injections of high dose LYB014 at 28-day intervals.
干预措施: LYB014 high dose (Biological)
Low dose of LYB017
Young adults (18-59 years old) will receive three injections of low dose LYB017 at 28-day intervals.
干预措施: LYB017 low dose (Biological)
High dose of LYB017
Young adults (18-59 years old) will receive three injections of high dose LYB017 at 28-day intervals.
干预措施: LYB017 high dose (Biological)
Low dose of LYB027
Young adults (18-59 years old) will receive three injections of low dose LYB027 at 28-day intervals.
干预措施: LYB027 low dose (Biological)
High dose of LYB027
Young adults (18-59 years old) will receive three injections of high dose LYB027 at 28-day intervals.
干预措施: LYB027 high dose (Biological)
Control A02B adjuvant
Young adults (18-59 years old) will receive three injections of A02B adjuvant at 28-day intervals.
干预措施: Control A02B adjuvant (Biological)
结局指标
主要结局
Immediate adverse events (AEs) within 30 minutes after each vaccination
时间窗: 30 mins after each vaccination
The incidence, severity and causality of any AEs within 30 minutes after each vaccination
Solicited local and systemic AEs and unsolicited AEs
时间窗: Within 7 days after each vaccination
The incidence, severity and causality of any solicited local and systemic AEs and unsolicited AEs within 7 days after each vaccination
Unsolicited AEs
时间窗: Within 28 days after each vaccination
The incidence, severity and causality of any unsolicited AEs within 28 days after each vaccination.
Serious adverse events (SAEs) and adverse events of special interest (AESIs)
时间窗: From the first vaccination through 336 days post the third vaccination
The incidence and causality of any SAEs and AESIs
次要结局
- The humoral immunogenicity (antibody response)(At baseline and 28 days post each vaccination and 84 days, 168 days and 336 days post the third vaccination.)