Phase 1 Study of the Safety and Immunogenicity of an Epstein-Barr Virus (EBV) gp350- Ferritin Nanoparticle Vaccine in Healthy Adults With or Without EBV Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 83
- 试验地点
- 1
- 主要终点
- Local and systemic reactogenicity; unsolicited adverse events; serious adverse events; change in neutralizing antibody responses to EBV
研究概览
简要总结
Background:
Epstein-Barr virus (EBV) causes most cases of infectious mononucleosis (mono). Up to 1 in 10 people who get mono can have fatigue that lasts more than 6 months. One out of 100 people can have severe complications. EBV is also associated with several types of cancer. Researchers want to test an EBV vaccine.
Objective:
To test the safety of and immune response to a new vaccine against EBV.
Eligibility:
Healthy adults ages 18-29
Design:
Participants will be screened with a medical history and physical exam. They will give a blood sample.
Screening tests will be repeated during the study.
Participants will get a dose of the study vaccine as an injection in a muscle in the upper arm. They will be observed for 30 to 60 minutes. Blood pressure, heart rate, breathing rate, and temperature will be checked. The injection site will be examined.
Participants will get a diary card. They will write down any side effects they have after the vaccine dose, or they may use an electronic diary card. Participants will be asked to write down or enter any important medical events that may occur at any time during the study.
Participants will get a vaccine dose at 2 more study visits. They will have 4 follow-up visits at different times after a vaccine dose.
Participants will have 6 telephone calls in between the in-person visits. They will also have 1 telephone call 1 year after the third dose of vaccine. If possible, this visit can occur in person.
Participation will last about 18 months. There is an optional in-person visit or telephone call 2 years after the third dose of vaccine.
详细描述
Study Description:
Phase 1 study to evaluate the safety and immunogenicity of a 3-dose vaccination regimen of an adjuvanted EBV gp350-Ferritin nanoparticle vaccine. Based on data reported in animal studies, our hypothesis is that this EBV vaccine will be safe and will induce a potent EBVgp350-specific immune response. Twenty EBV seropositive participants and 20 EBV seronegative participants will receive 3 doses of vaccine at 0, 1, and 6 months. Subjects will be followed until 12 months after the third dose of vaccine with an option to be followed for an additional year.
Objectives:
Primary objective: To determine the safety and immunogenicity of an adjuvanted EBV gp350- Ferritin vaccine administered as three (3) intramuscular injections to healthy adults with or without prior EBV infection.
Secondary objective: To further evaluate the immunogenicity of an adjuvanted EBV gp350-Ferritin vaccine administered to healthy adults.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 29 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- •18 to 29 years old
- •Screening procedures and evaluations performed no more than 30 days prior to scheduled administration of the first vaccine dose.
- •Ability of subject to understand and the willingness to sign a written informed consent document.
- •Stated willingness to comply with all study procedures and availability for the duration of the active phase of the study (approximately 18 months)
- •Willingness to allow storage of blood and saliva for future research.
- •In good general health as evidenced by medical history, physical examination, and laboratory screening result.
- •Subject is willing to forgo receipt of a licensed, live vaccine in the 30 days preceding each dose of vaccine or in the 30 days following each dose of vaccine. An FDA-approved inactivated, subunit or replication-defective vaccine (such as COVID-19, influenza,
- •tetanus etc.) and/or a COVID-19 vaccine approved under emergency use authorization can be used >=14 days before or >=14 days after administration of the study vaccine.
- •For females of reproductive potential who are sexually active with a male partner: use of highly effective continuous contraception for at least 30 days prior to Day 0 and agreement to continue use until 60 days after the last dose of vaccine.
- •For males who are sexually active with partners of child-bearing potential: use of highly effective continuous contraception from Day 0 and agreement to continue use until 30 days after the last dose of vaccine.
- •Contraceptive requirements: Because the effects of EBV gp350-Ferritin vaccine on the developing human fetus are unknown, sexually active female participants of childbearing potential must agree to use highly effective contraception as outlined below before study entry and until 60 days after the last dose of vaccine. Females of childbearing potential must have a negative pregnancy test before receiving each dose of the EBV gp350-Ferritin vaccine. During the course of the study, if a participant becomes pregnant or suspects they are pregnant, then they should inform the study staff and their primary care physician immediately. Acceptable forms of contraception are:
- •Intrauterine device (IUD) or equivalent
- •Hormonal contraceptive (e.g. consistent, timely, and continuous use of contraceptive pill, patch, ring, implant, or injection that has reached full efficacy prior to dosing). If the participant uses a contraceptive pill, path, or ring, then a barrier method (e.g. male/female condom, cap or diaphragm plus spermicide) must also be used at the time of potentially reproductive sexual activity.
- •A stable, long-term monogamous relationship with a partner who does not pose any potential pregnancy risk, e.g. has undergone a vasectomy at least 6 months prior to the first dose of vaccine or is of the same sex as the participant.
- •A hysterectomy and/or a bilateral tubal ligation or bilateral oophorectomy
- •Acceptable forms of contraception for male participants include one of the following:
- •Condom plus spermicide, used before or during sexual intercourse, even if the female partner uses a contraceptive pill, patch, or ring
- •A vasectomy completed at least 6 months before the first dose of vaccine
- •Continuously and completely abstaining from sexual intercourse with a female with child-bearing potential from the first dose of vaccine until 30 days after the last dose.
- •Acceptable contraception for female partners with child-bearing potential of male study participants include one of the following:
- •IUD or equivalent
- •Hormonal contraceptive (e.g. pill, patch, ring, implant or an injection used consistently and that has reached full effect prior to the first dose of vaccine)
- •Hysterectomy and/or a bilateral tubal ligation or bilateral oophorectomy
- •Laboratory Criteria within 30 days or less prior to enrollment:
- •Hemoglobin within institutional normal limits or if not, then assessed and deemed not clinically significant by PI or designee
- •White blood cell (WBC) count and differential either within institutional normal reference range or if not then assessed and deemed not clinically significant by PI or designee
- •Total lymphocyte count (lymphocyte absolute) >= 800 cells/mm3 (0.8 K/mcL)
- •Platelet count equal to 125,000 - 500,000/Mm^3 (125-500 K/mcL)
- •Alanine aminotransferase (ALT) <= 1.25x upper limit of normal (ULN)
- •Serum immunoglobulin G (IgG) > 600 mg/dL
- •Negative human immunodeficiency virus (HIV) test.
排除标准
- •An individual who meets any of the following criteria will be excluded from participation in this study:
- •Women who are breastfeeding or planning to become pregnant while participating through 60 days after the last dose of vaccine
- •Participant has received any of the following:
- •More than 10 days of systemic immunosuppressive medications (>=10 mg prednisone dose or its equivalent) or cytotoxic medication within the 30 days prior to first dose of vaccine or immunomodulating therapy within 180 days prior to first dose of vaccine.
- •Blood products, including immunoglobulin products, within 120 days prior to first dose of vaccine
- •Any live attenuated vaccination within 30 days prior to first dose of vaccine
- •Medically indicated subunit inactivated or replication-defective vaccines, e.g. influenza, pneumococcal, COVID-19 within 14 days of the first dose of vaccine.
- •Investigational research agents within 30 days prior to first dose or planning to receive investigational products while on study
- •Allergy treatment with antigen injections, unless on a maintenance schedule of shots no more frequently than once per month.
- •Participant has any of the following:
- •Febrile illness within 14 days of the first dose of vaccine
- •Obesity, in which any of the following are true:
- •The deltoid muscle cannot be clearly identified
- •Intramuscular (IM) vaccine administration/dosing may be compromised
- •Presence of medical comorbidities such that enrollment is not in the best interests of the participant
- •Serious reactions to vaccines
- •Hereditary, acquired, or idiopathic forms of angioedema
- •Idiopathic urticaria within the past year
- •Asthma that is not well-controlled or required emergent care, urgent care, hospitalization or intubation during the past 2 years or that requires the use of oral or intravenous steroids
- •Diabetes mellitus type 1 or type 2, excluding a history of gestational diabetes
- •Clinically significant autoimmune disease or immunodeficiency
- •Hypertension that is not well-controlled
- •Thyroid disease that is not well-controlled
- •Bleeding disorder diagnosed by doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
- •Significant bruising or bleeding difficulties with IM injections or blood draws
- •Malignancy that is active or treated malignancy for which there is no reasonable assurance of sustained cure or malignancy that is likely to recur during the study period
- •Seizure disorder other than a history of 1) febrile seizures 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures that have not required treatment within the past 3 years
- •Asplenia, functional asplenia or any condition resulting in absence or removal of the spleen.
- •History of Guillain-Barre Syndrome
- •Alcohol or drug abuse or addiction
- •Any medical, psychiatric, or social condition that, in the judgement of the investigator, is a contraindication to protocol participation or impairs the participant s ability to give informed consent.
研究组 & 干预措施
EBV gp_350 Ferritin Vaccination
Adult participants with or without prior EBV infection will receive 3 doses of vaccine
干预措施: Matrix-M1 (Other)
Epstein-Barr Virus (EBV) seronegative participants
Participant seronegative for Epstein-Barr Virus (EBV) infection received three doses of the EBV gp350-Ferritin Vaccine 50 µg intramuscularly on study days 0, 30, and 180 with follow-up visits occurring after each dose of vaccine. In addition to vaccine dosing days, mandatory in-person visits occurred in the first week after the first dose of vaccine, one month after the second and third doses of vaccine, and six months after the third dose of vaccine.
干预措施: EBV gp350-Ferritin Vaccine (Biological)
Epstein-Barr Virus (EBV) seropositive participants
Participant seropositive for Epstein-Barr Virus (EBV) infection received three doses of the EBV gp350-Ferritin Vaccine 50 µg intramuscularly on study days 0, 30, and 180 with follow-up visits occurring after each dose of vaccine. In addition to vaccine dosing days, mandatory in-person visits occurred in the first week after the first dose of vaccine, one month after the second and third doses of vaccine, and six months after the third dose of vaccine.
干预措施: EBV gp350-Ferritin Vaccine (Biological)
结局指标
主要结局
Local and systemic reactogenicity; unsolicited adverse events; serious adverse events; change in neutralizing antibody responses to EBV
时间窗: Reactogenicity during the 7-day period after each dose; unsolicited adverse events up to 30 days after each dose; serious adverse events through 1 month after the third dose:; neutralizing antibody response one month after third dose
-Local reactogenicity: pain, tenderness, redness, bruising, swelling; Systemic reactogenicity symptoms: headache, muscle pain, fatigue, chills, oral temperature, joint pain, nausea/ vomiting, diarrhea; Change in log10 antibody response to EBV from baseline to 1 month after third dose of vaccine(Day 210) as measured by neutralization assay.
Number of Participants With Solicited Local Adverse Events (AEs)
时间窗: During the 7-day period after each dose of vaccine
Number of participants with at least one solicited local adverse events occurring within seven days of each vaccine dose administration. Local reactogenicity included injection site pain, injection site redness, injection site bruising, and injection site swelling. Adverse events were captured by investigator examination and history from participants.
Number of Participants With Solicited Local Adverse Events (AEs) (by Severity)
时间窗: During the 7-day period after each dose of vaccine
The severity of local adverse event was graded using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Clinical Trials. Grade 1: Pain = does not interfere with activity; Tenderness = mild discomfort to touch; Erythema/Redness = 2.5-5 cm; Induration/Swelling = 2.5-5 cm and does not interfere with activity Grade 2: Pain = Repeated use of non-narcotic pain reliever \> 24 hours or interferes with daily activity; Tenderness= Discomfort with movement; Erythema/Redness = 5.1-10 cm; Induration/Swelling = 5.1-10 cm and interferes with activity Grade 3: Pain = Any use of narcotic pain reliever or prevents daily activity; Tenderness = Significant discomfort at rest; Erythema/Redness = \> 10 cm; Induration/Swelling = \> 10 cm or prevents daily activity Grade 4: Pain = Emergency room (ER) visit or hospitalization; Tenderness = ER visit or hospitalization; Erythema/Redness = Necrosis or exfoliative dermatitis; induration/Swelling = Necrosis
Number of Participants With Solicited Systemic Adverse Events (AEs)
时间窗: During the 7-day period after each dose of vaccine
Number of participants with solicited systemic adverse events occurring within seven days of each vaccine dose administration. Systemic reactogenicity events included headache, muscle pain, fatigue, chills, fever, joint pain, nausea, vomiting, and diarrhea. Adverse events were captured by investigator examination and history from participants.
Number of Participants With Solicited Systemic Adverse Events (AEs) (by Grade)
时间窗: During the 7-day period after each dose of vaccine
The severity of systemic adverse events occurring after the administration of each vaccine dose was assessed using the grading scale below: Grade 1: Fever = 37.5\^oC-37.9\^oC; Fatigue, Headache, Myalgia = No interference with activity; Nausea = no interference with activity or 1-2 episodes/hour Grade 2: Fever = 38\^oC-38.4\^oC; Fatigue, Myalgia = Some interference with activity; Headache = Repeated use of non-narcotic pain reliever \> 24 hours or some interference with activity; Nausea = Some interference with activity or \> 2 episodes/24 hours Grade 3: Fever = 38.5\^oC-39.5\^oC; Fatigue = Prevents daily activity; Headache =Significant; any use of narcotic pain reliever or prevents daily activity; Myalgia =Significant; prevents daily activity; Nausea = Prevents daily activity, requires outpatient intravenous hydration Grade 4: Fever = \> 39.5\^oC; Fatigue, Headache, Myalgia = Emergency room (ER) visit or hospitalization; Nausea = ER visit or hospitalization for hypotensive shock
Number of Related Serious Adverse Events (AEs)
时间窗: Within one month after the third dose of vaccine (Day 180 through day 210)
Number of related serious adverse events (AEs) based on the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Clinical Trials. Serious adverse event is defined as any local or systemic adverse event that * is a life-threatening event, or * an AE that requires inpatient hospitalization or prolongs an existing hospitalization, or * results in a persistent or significant incapacity, or * substantial disruption of the ability to conduct normal life functions, or * is a congenital anomaly/birth defect/miscarriage/still birth, or -- results in death
Number of Related Unsolicited Adverse Events
时间窗: Within 30 days after each dose of vaccine
Number of related unsolicited adverse events (AEs) occurring within 30 days of each vaccine dose administration. Unsolicited adverse event is defined as an adverse event that is not specifically asked.
Number of Unrelated Unsolicited Adverse Events
时间窗: Within 30 days after each dose of vaccine
Number of related unsolicited adverse events (AEs) occurring within 30 days of each vaccine dose administration. Unsolicited adverse event is defined as an adverse event that is not specifically asked.
Change in Neutralizing Antibody Responses to Epstein-Barr Virus (EBV) gp350-Ferritin Vaccine
时间窗: Day 0 and Day 210
Change in log10 neutralizing antibody response to Epstein-Barr Virus (EBV) gp350-Ferritin vaccine from day 0 (baseline) to 30 days (Day 210) after the third dose of vaccine as measured by neutralization assay. Serum titer levels were analyzed as geometric means with 95% confidence intervals. Change = 30 days compared to baseline.
次要结局
- Change in antibody responses to EBV gp350; change in CD4+ T cell responses to EBV gp350(Change in antibody responses and change in CD4 T cell responses at 1 month after third dose of vaccine)
- Change in Antibody Responses to EBV gp350; Change in CD4+ T Cell Responses to EBV gp350(Change in antibody responses and change in CD4 T cell responses at 1 month after third dose of vaccine)