A Randomized, Observer-Blinded, Dose-Escalation Phase 1 Study to Assess the Safety and Immunogenicity of Three Different Dose Levels of a Live-Attenuated Chikungunya Virus Vaccine Candidate (VLA1553) in Healthy Volunteers Aged 18 To 45 Years
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 3
- 主要终点
- Frequency of solicited systemic reactions
研究概览
简要总结
Randomized, observer-blinded, multicenter, dose-escalation Phase 1 clinical study investigating three dose levels of VLA1553 after a single immunization.
120 study participants will be enrolled into the study to receive three different doses (30 subjects in the low and medium and 60 subjects in the high dose group). Vaccination will be given intramuscularly on Day 0. As safety precaution, the study will begin with enrolment of 20 sentinel subjects in an open-label fashion. Thereafter, subjects will be enrolled in a blinded, randomized manner in the three study arms.
A re-vaccination will be given at Month 6 or Month 12 to confirm that a single vaccination will be sufficient to induce high titer neutralizing antibodies and protect subjects from CHIKV viremia.
Study participants will be followed up until 13 months after initial vaccination.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged 18 to 45 years on the Day of screening;
- •Has a BMI of ≥ 18.5 and < 30 kg/m2 on the Day of screening;
- •Understanding of the study and its procedures, agrees to its provisions, and gives written informed consent prior to any study-related procedures;
- •Generally healthy as determined by the Investigator's clinical judgement based on medical history, physical examination and screening laboratory tests;
- •If female, subject is of non-childbearing potential. The definition of non-childbearing potential includes the following:
- •Surgically sterile (e.g., hysterectomy with or without oophorectomy; fallopian tube ligation; endometrial ablation), at least 30 days prior to signature of the Informed Consent form;
- •At least 5 years post-menopause (i.e., 6 years post last menstrual period), or menopause confirmed by follicle-stimulating hormone (FSH) testing.
排除标准
- •History of known CHIKV infection;
- •Plans to travel to areas with active CHIKV transmission during the course of the study or history of travel to an endemic CHIKV area within 4 weeks prior to study enrollment;
- •Participation in a clinical study involving an investigational CHIKV vaccine;
- •Receipt of an inactivated vaccine within 4 weeks or live vaccine within 8 weeks prior to vaccination in this study;
- •Positive test results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV);
- •(1) Abnormal laboratory liver function values (≥ grade 1), (2) any grade 1 abnormal lab values deemed clinically relevant by the Investigator, and (3) any ≥ grade 2 abnormal lab values irrespective of clinical significance at screening;
- •Clinically significant abnormal ECG at screening;
- •History of significant cardiovascular, respiratory (including asthma), metabolic, neurological, hepatic, rheumatic, autoimmune, hematological, gastrointestinal or renal disorder;
- •History of immune-mediated or clinically significant arthritis/arthralgia;
- •History of malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved a cure;
- •Disease or recent or current treatment that can be expected to influence immune response as specified in the protocol;
- •History of severe hypersensitivity reactions or anaphylaxis;
- •History of any vaccine related contraindicating event (e.g., anaphylaxis, allergy to components of the candidate vaccine, other known contraindications);
- •Acute febrile infections within two weeks prior to vaccination;
- •Subject is of childbearing potential or lactating at the time of enrollment;
- •Blood donation within 30 days or receipt of blood-derived products (e.g. plasma) within 90 days prior to vaccination in this study or during the course of the study;
- •A rash, dermatological condition or tattoos that would, in the opinion of the Investigator, interfere with injection site reaction rating;
- •Known or suspected problem with alcohol or drug abuse as determined by the Investigator;
- •Any condition that, in the opinion of the Investigator, may compromise the subjects well-being, might interfere with evaluation of study endpoints, or would limit the subject's ability to complete the study;
- •Participation in another clinical study involving an investigational medicinal product within 30 days prior to study enrollment or during the course of this study;
- •Member of the team conducting the study or in a dependent relationship with one of the study team members. Dependent relationships include close relatives (i.e., children, partner/spouse, siblings, parents) as well as employees of the Investigator or site personnel conducting the study.
研究组 & 干预措施
VLA1553 high dose
VLA1553 with 3.2x10^5 TCID50/ 1 mL Re-vaccination at Month 6 or Month 12 with VLA1553 with 3.2x10^5 TCID50/ 1 mL
干预措施: VLA1553 (Biological)
VLA1553 low dose
VLA1553 with 3.2x10^3 TCID50/ 100 µL (microliter). Re-vaccination at Month 12 with VLA1553 with 3.2x10^5 TCID50/ 1 mL (milliliter)
干预措施: VLA1553 (Biological)
VLA1553 medium dose
VLA1553 with 3.2x10^4 TCID50/ 1 mL Re-vaccination at Month 12 with VLA1553 with 3.2x10^5 TCID50/ 1 mL
干预措施: VLA1553 (Biological)
结局指标
主要结局
Frequency of solicited systemic reactions
时间窗: up to Day 14 after single vaccination
Systemic reactions including fever, nausea/vomiting, headache, fatigue, myalgia (muscle pain), arthralgia (joint pain) and rash will be reported in a standardized manner
Severity of solicited injection site reactions
时间窗: up to Day 14 after single vaccination
Any measurable injection site reaction will be measured by size and includes injection site pain, tenderness, erythema/redness, induration and swelling. They will be rated according to the Severity Grading Scale of Injection Site Reactions (FDA Guidance on Toxicity Grading Scales for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA 2007)
Frequency of solicited injection site reactions
时间窗: up to Day 14 after single vaccination
Any measurable injection site reaction will be measured by size and includes injection site pain, tenderness, erythema/redness, induration and swelling.
Severity of solicited systemic reactions
时间窗: up to Day 14 after single vaccination
Systemic reactions including fever, nausea/vomiting, headache, fatigue, myalgia (muscle pain), arthralgia (joint pain) and rash will be reported in a standardized manner. They will be rated according to the FDA Guidance on Toxicity Grading Scales
次要结局
- Severity of solicited injection site reactions(until Day 14, Day 28 and throughout the study period)
- Frequency of solicited systemic reactions(until Day 14, Day 28 and throughout the study period)
- Assessment of viremia after each vaccination(on Days 3, 7, 14 and beyond Day 14 after re-vaccination)
- Frequency of any adverse event (AE)(until Day 14, Day 28 and throughout the study period)
- Frequency of solicited injection site reactions(until Day 14, Day 28 and throughout the study period)
- Immune response as measured by CHIKV-specific neutralizing antibody titer as determined by micro-neutralization (μNT) assay.(Day 28, Day 84, Month 6, Month 12, and 28 days after re-vaccination)
- Severity of any adverse event (AE)(until Day 14, Day 28 and throughout the study period)
- Severity of solicited systemic reactions(until Day 14, Day 28 and throughout the study period)