VRC 323: A Phase I Open-Label Clinical Trial to Evaluate the Dose, Safety, Tolerability and Immunogenicity of an Influenza H10 Stabilized Stem Ferritin Vaccine, VRC-FLUNPF0103-00-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
- 2
- 主要终点
- Number of Participants With Serious Adverse Events (SAEs) Following H10ssF-6473 Product Administration
研究概览
简要总结
Background: The flu is a common viral infection that can be deadly for certain people. Vaccines against flu have been developed to teach the body to prevent or fight the infection. A new vaccine may help the body to make an immune response to H10 flu, a flu strain that infects humans.
Objective:
To test the safety and effectiveness of the H10 Stabilized Stem Ferritin vaccine (VRC-FLUNPF0103-00-VP or H10ssF-6473).
Eligibility:
Healthy adults ages 18-70, but not born between 1965-1970
Design:
Participants received 1 or 2 vaccinations by injections (shots) in the upper arm muscle over 4 months. Participants received a thermometer and recorded their temperature and symptoms every day on/with/via a diary card for 7 days after each injection. The injection site was checked for redness, swelling, itching or bruising.
Participants had 8-10 follow-up visits over 10 months. At follow-up visits, participants had blood drawn and were checked for health changes or problems. Participants who reported influenza-like illness had nose and throat swabs collected for evaluation of viral infection.
Some participants had apheresis. A needle was placed into a vein in both arms. Blood was removed through a needle in the vein of one arm. A machine removed the white blood cells and then the rest of the blood was returned to the participant through a needle in the other arm.
详细描述
Design: This was a Phase I, open-label, dose escalation study to evaluate the dose, safety, tolerability, and immunogenicity of VRC-FLUNPF0103-00-VP in two regimens. The hypotheses were that the vaccine is safe and tolerable and would elicit an immune response. The primary objective was to evaluate the safety and tolerability of the investigational vaccine in healthy adults. Secondary objectives were related to immunogenicity of the investigational vaccine and dosing regimen.
Study Products: The investigational vaccine, VRC-FLUNPF0103-00-VP (H10ssF-6473), was developed by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID) and is composed of the haemagglutinin (HA) stem domain from A/Jiangxi/IPB13/2013 (H10N8) influenza genetically fused to the ferritin protein from Helicobacter pylori. Purified H10ssF-6473 displays eight well-formed HA trimers that antigenically resemble the native H10 stem viral spikes. The vaccine was supplied in single-use vials at a concentration of 180 mcg/mL. VRC-PBSPLA043-00-VP consisting of sterile phosphate buffered saline (PBS) was the diluent for H10ssF-6473. Prepared study product was administered intramuscularly (IM) in the deltoid muscle via needle and syringe.
Participants:
Healthy adults between the ages of 18-70 were enrolled; adults born between 1965 and 1970 were excluded from the trial
Study Plan: This study evaluated the safety, tolerability and immunogenicity of 1 or 2 doses of H10ssF-6473 in a dose-escalation design.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 Participants With Serious Adverse Events (SAEs) Following H10ssF-6473 Product Administration
时间窗: Day 0 after H10ssF-6473 product administration through the study participation, up to Week 40
SAEs were recorded from receipt of first study product administration through the last expected study visit at Week 40. 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 participant with multiple experiences of the same event is counted once using the event of worst severity.
Number of Participants With Influenza or Influenza-like Illness (ILIs) Following H10ssF-6473 Product Administration
时间窗: Day 0 after H10ssF-6473 product administration through the study participation, up to Week 40
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. ILI was defined as fever (temperature of 100 degrees F \[37.8 degrees C\] or greater) and a cough and/or sore throat in the absence of a known cause other than influenza. Collection of nasopharyngeal swabs were used for laboratory confirmation of influenza by polymerase chain reaction (PCR) in participants who met criteria for ILI. Subsequently, results of any reported laboratory testing for identification of pathogens were included for cases meeting initial criteria for ILI. The severity of illness in participants with laboratory confirmed influenza illness were captured on a case report form rather than on an Adverse Event (AE) form.
Number of Participants With New Chronic Medical Conditions Following H10ssF-6473 Product Administration
时间窗: Day 0 after H10ssF-6473 product administration through the study participation, up to Week 40
New chronic medical conditions that required ongoing medical management were recorded from receipt of first study product administration through the last expected study visit at Week 40. The relationship between a new chronic medical condition and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.
Number of Participants With Abnormal Laboratory Measures of Safety Following H10ssF-6473 Product Administration
时间窗: Day 0 after H10ssF-6473 product administration through the study participation, up to Week 40
Abnormal lab results recorded as unsolicited adverse events (AEs) are summarized. Safety lab 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 Day 14, 28, and 280 (Group 1) or at Day 14, 28, 112, 140 and 280 (Groups 2A-2B). Iron and serum ferritin were collected at Day 28 (Group 1) or at Days 112 and 140 (Groups 2A-2B). Creatinine results were collected at Day 14 (Group 1) or at Days 14 and 140 (Groups 2A-2B). Institutional lab normal ranges as well as Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials FDA Guidance, September 2007 were used.
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Each H10ssF-6473 Product Administration
时间窗: 7 days after each H10ssF-6473 product administration, at approximately Week 1 and at approximately Week 17
Participants 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. Participants 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 participants 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.
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Each H10ssF-6473 Product Administration
时间窗: 7 days after each H10ssF-6473 product administration, at approximately Week 1 and at approximately Week 17
Participants 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. Participants 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 participants 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 Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following H10ssF-6473 Product Administration
时间窗: Day 0 through 4 weeks after each H10ssF-6473 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 and new chronic medical conditions that required ongoing medical management (reported as separate outcomes) 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 participant with multiple experiences of the same event is counted once using the event of worst severity.
次要结局
- Stem-Specific Antibody Response to H10ssF-6473 Following the Completion of Each Vaccination Regimen(Baseline to 2 weeks after the single or first injection, at Week 2 and from Week 16 to 2 weeks after the second injection, at Week 18)