VRC 316: A Phase I Open-Label Clinical Trial To Evaluate Dose, Safety, Tolerability, And Immunogenicity Of An Influenza HA Ferritin Vaccine, Alone Or In Prime-Boost Regimens With An Influenza DNA Vaccine In Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Number of Subjects With Serious Adverse Events (SAEs) Following DNA A/Sing Product Administration
研究概览
简要总结
Background:
Influenza, or "flu", is a very common infectious respiratory disease. Researchers want to develop a vaccine against flu. Vaccines teach the body to fight or prevent an infection. When the body learns to fight an infection, this is called an immune response. In this study, researchers want to test two new vaccines to help the body make an immune response to flu.
Subjects received the vaccine injections in the upper arm muscle. One vaccine, the influenza HA Ferritin vaccine (HA-F A/Sing), was given to all subjects with a needle injection. The other vaccine, influenza DNA vaccine (DNA A/Sing), was given to subjects in Group 3 by a needle-free device that uses high pressure to push the vaccine through the skin and into the muscle.
Objective:
To test the safety and side effects of two new vaccines for prevention of H2 influenza (flu).
Eligibility:
Part I: Healthy adults ages 18-47 born after 1969.
Part II: Healthy adults ages 18-70, but not born in 1966-1969.
Design:
Volunteers were tested for eligibility in a separate screening protocol.
In Part I, all subjects received injections of HA Ferritin vaccine. These subjects were not expected to have H2N2 exposure based on their age and when H2N2 last circulated in the population. Five subjects in Group 1 received one injection of 20 mcg dose vaccine at Day 0 to test if it is safe. Then, five additional subjects in Group 2 received a total of two injections of a 60 mcg dose on Day 0 and 16 weeks later.
In Part II, responses were evaluated from adults born before 1966 who may have prior potential exposure to H2N2 influenza as well as adults similar to those enrolled in Part I who are not expected to have H2N2 exposure. Also, Part II compared responses to 2 different vaccine regimens. Group 3 subjects received a DNA influenza vaccine prime at Day 0 and the HA Ferritin vaccine boost 16 weeks later. Group 4 subjects received the HA Ferritin vaccine 2 times, on Day 0 and 16 weeks later.
详细描述
Study Design: This is a Phase I open-label, dose escalation study to evaluate the dose, safety, tolerability, and immunogenicity of VRC-FLUNPF081-00-VP (HA-F A/Sing) vaccine alone or in prime-boost regimens with VRC-FLUDNA082-00-VP (DNA A/Sing) vaccine. The hypotheses are that VRC-FLUNPF081-00-VP and VRC-FLUDNA082-00-VP vaccines are safe, well-tolerated, and induce an immune response to the H2 antigen. The primary objectives are to evaluate the safety and tolerability of two different doses of the HA-F A/Sing vaccine alone and in prime-boost regimens in healthy adults. Secondary objectives are related to the evaluation of the immunogenicity of the HA-F A/Sing and DNA A/Sing vaccines in prime-boost regimens.
Study Products: The investigational HA-F A/Sing vaccine, developed by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), is composed of Helicobacter pylori non-haem ferritin with an influenza virus H2 hemagglutinin (HA) insert to form a nanoparticle displaying eight HA trimers from A/Singapore/1/57 (H2N2) influenza.
The investigational DNA A/Sing vaccine, developed by the VRC, NIAID, is composed of a single closed-circular DNA plasmid that encodes the H2 protein of A/Singapore/1/57 influenza.
Subjects: Up to 80 healthy adults ages 18-70 were enrolled; adults born between 1966 and 1969 were excluded from the trial.
Study Plan: Vaccines were administered intramuscularly (IM) in the deltoid muscle. This study has two parts:
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Number of Subjects With Serious Adverse Events (SAEs) Following DNA A/Sing Product Administration
时间窗: Day 0 through Day 280
SAEs were recorded from receipt of first study product administration through the last expected study visit at Day 280. 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 Within 7 Days of DNA A/Sing Product Administration
时间窗: 7 days after DNA A/Sing product administration, at approximately Week 1
Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after the DNA A/Sing 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 more than one time 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 (FDA Guidance - September 2007).
Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Each HA-F A/Sing Product Administration
时间窗: 7 days after each HA-F A/Sing product administration, at approximately Week 1 and/or at approximately Week 17
Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after each HA-F A/Sing 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 more than one time 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 (FDA Guidance - September 2007).
Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of DNA A/Sing Product Administration
时间窗: 7 days after DNA A/Sing product administration, at approximately Week 1
Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after DNA A/Sing 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 more than one time 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 (FDA Guidance - September 2007).
Number of Subjects With Abnormal Laboratory Measures of Safety
时间窗: Day 0 through Day 280
Any abnormal laboratory results recorded as unsolicited adverse events (AEs) are summarized. Safety laboratory parameters included hematology (hemoglobin, hematocrit, platelets, and white blood cell (WBC), red blood cell (RBC), neutrophil, lymphocyte, monocyte, eosinophil and basophil percents/counts) and chemistry (alanine aminotransferase (ALT), alanine aspartate (AST), alkaline phosphate (ALP), creatinine and total bilirubin). Complete blood count (CBC) with differential, total bilirubin, AST, ALT, and ALP results were collected at screening (≤ 84 days before enrollment), Day 0 prior to study product administration (baseline), and at Days 14, 28, 112, 140 and 280. Creatinine results were collected at screening, Day 0 and Day 6. Institutional laboratory normal ranges as well as the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials FDA Guidance, September 2007 were used.
Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Each HA-F A/Sing Product Administration
时间窗: 7 days after each HA-F A/Sing product administration, at approximately Week 1 and/or at approximately Week 17
Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after each HA-F A/Sing 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 more than one time 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 (FDA Guidance - September 2007).
Number of Subjects With One or More Unsolicited Non-Serious Adverse Events (AEs) Following DNA A/Sing Product Administration
时间窗: Day 0 through 4 weeks after DNA A/Sing product administration, up to Week 4
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), influenza-like illness (ILI) or influenza (reported as a separate outcome) 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 Influenza or Influenza-like Illness (ILIs) Following HA-F A/Sing Product Administration
时间窗: Day 0 through Day 280
Influenza or influenza-like illness (ILI) were recorded in the study database from receipt of the first study product administration through the last study visit.
Number of Subjects With One or More Unsolicited Non-Serious Adverse Events (AEs) Following Each HA-F A/Sing Product Administration
时间窗: Day 0 through 4 weeks after each HA-F A/Sing product administration, up to Week 20
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), influenza-like illness (ILI) or influenza (reported as a separate outcome) 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 Influenza or Influenza-like Illness (ILIs) Following DNA A/Sing Product Administration
时间窗: Day 0 through Day 280
Influenza or influenza-like illness (ILI) were recorded in the study database from receipt of the first study product administration through the last study visit.
Number of Subjects With Serious Adverse Events (SAEs) Following HA-F A/Sing Product Administration
时间窗: Day 0 through Day 280
SAEs were recorded from receipt of first study product administration through the last expected study visit at Day 280. 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.
次要结局
- Pseudoviral Neutralization Assay Geometric Mean Titer (GMT) Against A/Singapore/1/1957 (H2N2) Following the Completion of Each Vaccine Regimen(Four weeks after the first dose for groups that received a single vaccination, at Week 4 or two weeks after the second dose for groups that received two vaccinations, at Week 18)
- Seroconversion Rate Following the Completion of Each Vaccine Regimen(Four weeks after the first dose for groups that received a single vaccination, at Week 4 or two weeks after the second dose for groups that received two vaccinations, at Week 18)
- Hemagglutination Inhibition Assay (HAI) Geometric Mean Titer (GMT) Against A/Singapore/1/1957 (H2N2) Following the Completion of Each Vaccine Regimen(Four weeks after the first dose for groups that received a single vaccination, at Week 4 or two weeks after the second dose for groups that received two vaccinations, at Week 18)