VRC 311: A Phase 1 Open Label, Dose-Escalation Clinical Trial to Evaluate the Safety and Immunogenicity of a Virus-Like Particle (VLP) Chikungunya Vaccine, VRC-CHKVLP059-00-VP, in Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of First Vaccination
研究概览
简要总结
Background:
- Chikungunya virus (CHIKV) is transmitted by mosquitoes. It can cause fever, headache, muscle pain, fatigue, and joint pain. The disease usually does not cause death. But the joint pain, which may be directly related to the infecting virus, may be severe and last for several months. CHIKV outbreaks are most common in Africa, India, and Asia. A new experimental vaccine for CHIKV has been developed, and researchers are testing it in healthy adults. Participants cannot develop CHIKV from this vaccine.
Objectives:
- To test the safety and effectiveness of a Chikungunya virus vaccine.
Eligibility:
- Healthy individuals between 18 and 50 years of age.
Design:
- This study, including vaccine doses and followup tests, will last about 44 weeks. Participants will have three vaccination visits, six followup clinic visits, and three telephone contacts during this study. Vaccination visits will take about 4 hours. Most other clinic visits will usually take 2 hours. The telephone contacts will take about 15 minutes.
- Participants will be screened with a physical exam and medical history. Blood samples will also be collected.
- Participants will be assigned to one of three dose groups. Information about doses will be provided before the start of the vaccinations.
- Vaccine injections will be given at the start of the study, at 4 weeks, and at 20 weeks. Participants will be asked to keep an eye on the injection site for 7 days and to notify researchers if there are any side effects.
- Participants will be monitored throughout the study with blood samples and clinic visits.
详细描述
This is a Phase I, open-label, dose-escalation study to examine the safety, tolerability, and immune response to a Virus-Like Particle (VLP) Chikungunya Virus (CHIKV) vaccine in healthy adults ages 18 to 50 years old. The plan is for 25 subjects to receive 3 intramuscular vaccine injections at weeks 0, 4, and 20. The three groups will be enrolled sequentially starting with the lowest dose of 10 micrograms per injection in Group 1.
The hypothesis is that the vaccine is safe and induces immune responses to CHIKV. The primary objective is to evaluate the safety and tolerability of the investigational vaccine, VRC-CHKVLP059-00-VP, at three dosages, 10 micrograms (mcg), 20 mcg, and 40 mcg, in healthy adults. The secondary objective is to evaluate the antibody response against CHIKV VLPs four weeks after the third vaccine injection. The exploratory objectives relate to antigen-specific humoral and cellular immune responses throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
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
- •A participant must meet all of the following criteria:
- •18 to 50 years old
- •Available for clinical follow-up through Week 44
- •Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
- •Complete an Assessment of Understanding prior to enrollment and verbalize understanding of all questions answered incorrectly
- •Able and willing to complete the informed consent process
- •Willing to donate blood for sample storage to be used for future research
- •In good general health, with a BMI less than or equal to 40, without clinically significant medical history, and has satisfactorily completed screening
- •Physical examination and laboratory results without clinically significant findings within the 56 days prior to enrollment
- •Laboratory Criteria within 56 days prior to enrollment:
- •Hemoglobin greater than or equal to11.5 g/dL for women; greater than or equal to13.5 g/dL for men
- •WBC: 3,000-12,000 cells/mm(3).
- •Differential either within institutional normal range or accompanied by physician approval
- •Total lymphocyte count: greater than or equal to 800 cells/mm(3)
- •Platelets = 125,000-500,000/mm(3)
- •Alanine aminotransferase (ALT) less than or equal to 1.25 times upper limit of normal range
- •Serum creatinine less than or equal to1x upper limit of normal (less than or equal to1.3 mg/dL for females; less than or equal to1.4 mg/dL for males).
- •Negative FDA-approved HIV blood test
- •Female-Specific Criteria
- •Negative Beta-HCG pregnancy test (urine or serum) on day of enrollment for women presumed to be of reproductive potential
- •A woman of childbearing potential must agree to use an effective means of birth control from at least 21 days prior to enrollment through 12 weeks after last study vaccination
排除标准
- •A participant will be excluded if one or more of the following conditions apply:
- •Female-Specific Criteria
- •Woman who is breast-feeding or planning to become pregnant during the time projected for individual study participation
- •Systemic immunosuppressive medications or cytotoxic medications within 12 weeks prior to enrollment [with the exceptions that a short course of corticosteroids (less than or equal to10 days duration or a single injection) for a self-limited condition at least 2 weeks prior to enrollment will not exclude study participation]
- •Blood products within 16 weeks prior to enrollment
- •Immunoglobulin within 8 weeks prior to enrollment
- •Prior vaccinations with an investigational CHIKV vaccine
- •Investigational research agents within 4 weeks prior to enrollment
- •Live attenuated vaccines within 4 weeks prior to enrollment
- •Medically indicated subunit or killed vaccines, e.g. influenza, pneumococcal, or allergy treatment with antigen injections, within 2 weeks prior to enrollment
- •Current anti-TB prophylaxis or therapy
- •Subject has a history of any of the following clinically significant conditions:
- •A history of confirmed or suspected CHIKV infection
- •A history of immune-mediated or clinically significant arthritis
- •Serious reactions to vaccines that preclude receipt of study vaccinations as determined by the investigator
- •Hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms of angioedema
- •Asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the past two years or that is expected to require the use of oral or intravenous corticosteroids
- •Diabetes mellitus (type I or II), with the exception of gestational diabetes
- •Idiopathic urticaria within the past year
- •Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws
- •Malignancy that is active, or treated malignancy for which there is not reasonable assurance of sustained cure, or malignancy that is likely to recur during the period of the study
- •Seizure disorder other than: 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures that have not required treatment within the last 3 years
- •Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen
- •Psychiatric condition that may preclude compliance with the protocol; past or present psychoses; disorder requiring lithium; or within five years prior to enrollment, a history of suicide plan or attempt
- •Any medical condition (such as thyroid disease or hypertension that are not well controlled by medication, or viral hepatitis) that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent
研究组 & 干预措施
Group 3
Group 3 will receive three IM injections of VRC-CHKVLP059-00-VP (at weeks 0,4, and 20) at a dose of 40 mcg.
干预措施: VRC-CHKVLP059-00-VP (Biological)
Group 2
Group 2 will receive three IM injections of VRC-CHKVLP059-00-VP (at weeks 0,4, and 20) at a dose of 20 mcg.
干预措施: VRC-CHKVLP059-00-VP (Biological)
Group 1
Group 1 will receive three IM injections of VRC-CHKVLP059-00-VP (at weeks 0,4, and 20) at a dose of 10 mcg.
干预措施: VRC-CHKVLP059-00-VP (Biological)
结局指标
主要结局
Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of First Vaccination
时间窗: 7 days after the first vaccination
Subjects record the occurrence of solicited symptoms on a Memory Aid for 7 days after first vaccination and review the Memory Aid with clinic staff at follow a up visit. Subjects are counted once for each symptom if they indicated experiencing the symptom at any severity during the reporting period. The number reported for all local symptoms is the number reporting one or more local symptom at any severity.
Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Third Vaccination
时间窗: 7 days after the third vaccination
Subjects record the occurrence of solicited symptoms on a Memory Aid for 7 days after third vaccination and review the Memory Aid with clinic staff at follow a up visit. Subjects are counted once for each symptom if they indicated experiencing the symptom at any severity during the reporting period. The number reported for all local symptoms is the number reporting one or more local symptom at any severity.
Number of Subjects Reporting 1 or More Unsolicited Adverse Event
时间窗: 28 days after each vaccination
Unsolicited adverse events were recorded from enrollment through 28 days after the second vaccination; and from the third vaccination through 28 days after this vaccination. Between and after the indicated time periods, through the last expected study visit (i.e., 24 weeks after the third vaccination), only SAEs and new chronic medical conditions were recorded. The number of unsolicited events reported for Group 3 here is lower than the total number of adverse events in the Adverse Event Module, which reports both solicited and unsolicited adverse events.
Number of Subjects With an Any Abnormal Laboratory Result
时间窗: 44 weeks after first vaccination
Blood samples were collected for chemistry, CBC with differential, at baseline and weeks 2, 4, 6, 8, 20, 22, 24 and 44
Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Second Vaccination
时间窗: 7 days after the second vaccination
Subjects record the occurrence of solicited symptoms on a Memory Aid for 7 days after second vaccination and review the Memory Aid with clinic staff at follow a up visit. Subjects are counted once for each symptom if they indicated experiencing the symptom at any severity during the reporting period. The number reported for all local symptoms is the number reporting one or more local symptom at any severity.
Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Any Vaccination
时间窗: 7 days after any vaccination
Subjects record the occurrence of solicited symptoms on a Memory Aid for 7 days after any vaccination and review the Memory Aid with clinic staff at follow a up visit. Subjects are counted once for each symptom if they indicated experiencing the symptom at any severity during the reporting period. The number reported for all local symptoms is the number reporting one or more local symptom at any severity.
Number of Subjects Reporting Serious Adverse Events
时间窗: 44 weeks after first vaccination
Serious adverse events were collected at each study visit from the time of first vaccination through the final study visit at 44 weeks after the first vaccination.
Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of First Vaccination
时间窗: 7 days after the first vaccination
Subjects record the occurrence of solicited symptoms on a Memory Aid for 7 days after first vaccination and review the Memory Aid with clinic staff at follow a up visit. Subjects are counted once for each symptom if they indicated experiencing the symptom at any severity during the reporting period. The number reported for all systemic symptoms is the number reporting one or more systemic symptom at any severity.
Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Third Vaccination
时间窗: 7 days after the third vaccination
Subjects record the occurrence of solicited symptoms on a Memory Aid for 7 days after third vaccination and review the Memory Aid with clinic staff at follow a up visit. Subjects are counted once for each symptom if they indicated experiencing the symptom at any severity during the reporting period. The number reported for all systemic symptoms is the number reporting one or more systemic symptom at any severity.
Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Any Vaccination
时间窗: 7 days after any vaccination
Subjects record the occurrence of solicited symptoms on a Memory Aid for 7 days after any vaccination and review the Memory Aid with clinic staff at follow a up visit. Subjects are counted once for each symptom if they indicated experiencing the symptom at any severity during the reporting period. The number reported for all systemic symptoms is the number reporting one or more systemic symptom at any severity.
Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Second Vaccination
时间窗: 7 days after the second vaccination
Subjects record the occurrence of solicited symptoms on a Memory Aid for 7 days after second vaccination and review the Memory Aid with clinic staff at follow a up visit. Subjects are counted once for each symptom if they indicated experiencing the symptom at any severity during the reporting period. The number reported for all systemic symptoms is the number reporting one or more systemic symptom at any severity.
次要结局
- Chikungunya Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT)(24 weeks after the first vaccination)
- Chikungunya Antigen-specific ELISA Geometric Mean Titer (GMT)(24 weeks after the first vaccination)
- Chikungunya Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT)(Pre-vaccination (Week 0))