A Phase 1 Open Label, Dose-Escalation Clinical Trial to Evaluate the Safety and Immunogenicity of a Trivalent Virus-Like Particle (VLP) Encephalitis Vaccine, VRC-WEVVLP073-00-VP, in Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms For 7 Days After Each Product Administration
研究概览
简要总结
Western Equine Encephalitis Virus (WEEV), Eastern Equine Encephalitis Virus (EEEV), and Venezuelan Equine Encephalitis Virus (VEEV) are transmitted to humans by infected mosquitoes and can cause encephalitis (swelling of the brain) and other neurological manifestations, including fever, chills, discomfort, feeling sick, muscle pain and then headache, vomiting, restlessness, irritability, seizures, coma, and death.
Vaccines teach the body to prevent or fight an infection. When the body learns to fight an infection, this is called an immune response. Researchers developed a vaccine against Western, Eastern and Venezuelan equine encephalitis viruses to help the body make an immune response. There are no live or killed viruses in the vaccine, so you cannot get infected with any of these 3 viruses from getting the vaccine.
The experimental trivalent encephalitis vaccine, VRC-WEVVLP073-00-VP, is composed of Western equine encephalitis (WEE), Eastern equine encephalitis (EEE), and Venezuelan equine encephalitis (VEE) virus-like particles (VLP).
The purpose of this study is to test three doses (6 mcg, 30 mcg, and 60 mcg) of this experimental vaccine against Western, Eastern and Venezuelan equine encephalitis viruses.
详细描述
This is a Phase 1, randomized, open-label, dose-escalation study to examine the safety, tolerability, and immune response of three doses (6 mcg, 30 mcg, and 60 mcg) of the WEVEE vaccine (VRC-WEVVLP073-00-VP) alone or with alum adjuvant (VRC-GENMIX083-AL-VP) in a 2-product administration regimen.
Eligible subjects were randomized to WEVEE alone (Groups 1, 3, and 5) or WEVEE plus alum (Groups 2, 4, and 6, respectively) in each dose group. No more than 1 subject was randomized and vaccinated per day for the first 3 subjects at each dose. If the 6 mcg dose of WEVEE was assessed as not showing safety concerns by a Protocol Safety Review Team (PSRT), randomization began for Groups 3 and 4 (30 mcg WEVEE without alum and with alum, respectively). In a second safety review conducted on the first 3 subjects to receive 30 mcg, if the 30 mcg dose of WEVEE was assessed as not showing safety concerns by the PSRT, randomization began for Groups 5 and 6 (60 mcg WEVEE without and with alum, respectively).
The product was administered in the upper arm muscle as an intramuscular (IM) injection via needle and syringe at Day 0 and 8 weeks later.
For all groups, solicited reactogenicity was evaluated using a 7-day diary card. Assessment of vaccine safety included clinical observation and monitoring of hematological and chemical parameters at clinical visits throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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 volunteer must have met all of the following criteria:
- •Age 18 to 50 years
- •Available for clinical follow-up through 36 weeks after randomization
- •Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
- •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, without clinically significant medical history, and has satisfactorily completed screening
- •Physical examination and laboratory results without clinically significant findings within the 28 days prior to randomization
- •Laboratory Criteria within 28 days prior to randomization:
- •Hemoglobin within institutional normal range or accompanied by Principal Investigator (PI) or designee approval
- •White blood cell (WBC) and differential either within institutional normal range or accompanied by PI or designee approval
- •Total lymphocyte count: ≥800 cells/mm3
- •Platelets: 125,000-500,000/mm3
- •Alanine aminotransferase (ALT): ≤ 1.25 x upper limit of normal range
- •Serum creatinine: ≤1.1 x upper limit of normal
- •Negative for HIV infection by an FDA-approved method of detection
- •Criteria applicable to women of childbearing potential:
- •Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test (urine or serum) on day of randomization before receiving the study product
- •Agrees to use an effective method of birth control, if sexually active, from at least 21 days prior to randomization through the last study visit.
排除标准
- •A volunteer was excluded if one or more of the following conditions applied:
- •Female-Specific Criteria
- •Breast-feeding or planning to become pregnant while participating in the study
- •Volunteer received any of the following:
- •More than 10 days of systemic immunosuppressive medications or cytotoxic medications within the 4 weeks prior to randomization or any within the 14 days prior to randomization
- •Blood products within 16 weeks prior to randomization
- •Immunoglobulin within 8 weeks prior to randomization
- •Prior vaccinations with an investigational alphavirus vaccine
- •Investigational research agents within 4 weeks prior to randomization or planning to receive investigational products while on study
- •Live attenuated vaccines within 4 weeks prior to randomization
- •Inactivated vaccines within 2 weeks prior initial study vaccine administration unless approved by the PI
- •Current anti-tuberculosis (TB) prophylaxis or therapy
- •Volunteer has a history of any of the following clinically significant conditions:
- •A history of confirmed or suspected viral encephalitis infection
- •Serious reactions to vaccines that preclude receipt of study vaccinations as determined by the investigator
- •Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema
- •Asthma that is not well controlled
- •Diabetes mellitus (type I or type II) with the exception of gestational diabetes
- •Thyroid disease that is not well controlled
- •Hypertension that is not well controlled
- •Evidence of autoimmune disease or immunodeficiency
- •Idiopathic urticaria within the last year
- •Malignancy that is active or history of malignancy that is likely to recur during the study
- •Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with intramuscular (IM) product administration or blood draws
- •Seizure disorder other than: 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures or treatment for a seizure disorder within the last 3 years
- •Asplenia, functional asplenia or any condition resulting in absence or removal of the spleen
- •Psychiatric condition that precludes compliance with the protocol; past or present psychoses; or within 5 years prior to randomization, a history of suicide plan or attempt
- •Any other chronic or clinically significant medical, psychiatric or social condition that, in the judgement of the investigator is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent.
结局指标
主要结局
Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms For 7 Days After Each Product Administration
时间窗: 7 days after each product administration, at approximately Week 1 and Week 9
Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of subjects reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (modified from FDA Guidance - September 2007).
Number of Subjects With Abnormal Laboratory Measures of Safety
时间窗: Day 0 through Day 252
Any abnormal laboratory results recorded as unsolicited adverse events (AEs) are summarized. Safety laboratory parameters included hematology (hemoglobin, hemoglobin change from baseline, hematocrit, mean corpuscular volume (MCV), platelets, and white blood cell (WBC), red blood cell (RBC), neutrophil, lymphocyte, monocyte, eosinophil and basophil counts) and chemistry (alanine aminotransferase (ALT) and creatinine). Complete blood count (CBC), differential, platelet, and ALT results were collected at screening (≤ 28 days before enrollment), Day 0 prior to study product administration (baseline), and at Days 14, 28, 56, 70, 84, 168 and 252. Creatinine results were collected at screening, Day 0 and Day 56. Institutional laboratory normal ranges as well as the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials (modified from FDA Guidance, September 2007) were used.
Number of Subjects With One or More Unsolicited Non-Serious Adverse Events (AEs)
时间窗: Day 0 through 4 weeks of each study product administration, up to Week 12
Unsolicited AEs and attribution assessments were recorded in the study database from receipt of the first study product administration through the visit scheduled for 4 weeks after each study product administration. At other time periods between study product administrations and when greater than 4 weeks after the last study product administration, only serious AEs (SAEs reported as a separate outcome and in the AE module) and new chronic medical conditions that required ongoing medical management were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A subject with multiple experiences of the same event is counted once using the event of worst severity.
Number of Subjects With Serious Adverse Events (SAEs)
时间窗: Day 0 through Day 252
SAEs were reported from receipt of first study product administration through the last expected study visit at Day 252. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A subject with multiple experiences of the same event is counted once using the event of worst severity.
Number of Subjects Reporting Local Reactogenicity Signs and Symptoms For 7 Days After Each Product Administration
时间窗: 7 days after each product administration, at approximately Week 1 and Week 9
Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of subjects reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (modified from FDA Guidance - September 2007).
次要结局
- Percentage of Positive Responders at 4 Weeks After the Last Product Administration of VRC-WEVVLP073-00-VP (WEVEE) Alone Or With Alum Adjuvant(4 weeks after the last product administration, at Week 12)
- Antigen-specific Neutralizing Antibody Geometric Mean Titers (GMTs) at 4 Weeks After the Last Product Administration of VRC-WEVVLP073-00-VP (WEVEE) Alone Or With Alum Adjuvant(4 weeks after the last product administration, at Week 12)