Safety and Immunogenicity of HBAI20 Hepatitis B Vaccine in Naive Adults and Non-responders
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 2
- 主要终点
- Subjects With Local and/or General Adverse Events Irrespective of Severity
研究概览
简要总结
The purpose of this study is to determine whether the HBAI20 vaccine is safe and more immunogenic than the HBVaxPro-10µg in people who have never been vaccinated with a hepatitis B vaccine and in people who have been vaccinated 6 times with hepatitis B vaccine but do not have a protective anti hepatitis B antibody titer.
详细描述
Rationale: Worldwide, people are suffering from the consequences of Hepatitis B (HB) virus infection. Currently available vaccines are protective in most of the vaccinees, however, a small part of the population does not respond to these vaccines (non-responders). A new adjuvant (AI20) has been developed by CyTuVax to improve the standard Hepatitis B vaccine for the protection of non-responders. The AI20 adjuvant consists of depot-attached rhuIL-2 (aggregated Interleukin-2 molecules attached to alum), facilitating the slow release of highly concentrated IL-2 nano aggregates. As shown in preclinical experiments, vaccination of mice, rats, and rabbits with the new HBAI20 vaccine results in higher and earlier immune responses to Hepatitis B surface antigen (HBsAg) compared to vaccination with one of the standard Hepatitis B vaccines. This clinical study will be done in order to assess the safety of the AI20 adjuvant and test if the AI20 adjuvanted Hepatitis B vaccine induces protective antibody titers in the vaccinated non-responders.
Objective: In the current study we investigate the safety of the HBAI20 vaccine. Furthermore, the efficacy of the HBAI20 vaccine in non-responders is investigated.
Study design: Partly double blinded randomized controlled intervention phase I study, partly open-label phase I study.
Study population: Healthy volunteers (n=24) and registered non-responders (n=12), 18-59 years old, males and females.
Intervention: The study will include 3 groups. HB vaccine naïve healthy subjects are randomized into group 1 and 2 and registered non-responders are included in group 3.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •In good health as determined by the outcome of medical history, physical examination screening/baseline labs and clinical judgment of the clinical investigator
- •Age 18 to 59 years, inclusive at the time of enrolment
- •Willing and able to adhere to the study regimen
- •Having a signed informed consent form
- •Non-responders:
- •Documented non-responders: Subjects with documented two cycles of Hepatitis B vaccination (total of 6 vaccinations) and titer analysis that show that they have not developed the Hepatitis B antibody titer recommended after standard vaccination: anti-HBsAg antibody titer higher to 10mIU/ml.
排除标准
- •Any infectious disease at the time of screening and/or enrolment
- •Positive HIV, Hepatitis B virus or Hepatitis C virus serology
- •Positive anti-IL-2 antibody titer
- •Known or suspected immune deficiency
- •Known or suspected disease that influences the immune system including chronic allergies that require frequent anti-allergy medication, cancer and transplantation recipients
- •Known or suspected allergy to any of the vaccine components.
- •Dialysis patient
- •History of unusual or severe reactions to any previous vaccination
- •History of any neurologic disorder, including epilepsy and autism
- •Use of medication that influences the immune system (immune suppressive treatment)
- •Any vaccination within 3 months before screening
- •Blood donation within 1 month before screening
- •Administration of plasma (incl. immunoglobulins) or blood products within 12 months before screening
- •Participation in another clinical trial within 3 months before screening
- •Abnormal pre-treatment laboratory parameters which are clinically relevant according to the investigator
- •Bleeding disorders, or use of medication for bleeding disorders, and use of anti-coagulants
- •Female subjects planning to become pregnant or breastfeeding babies until visit 7
- •Females: positive urine pregnancy test. Urine test positive at screening date or positive urine pregnancy test on the day of vaccination
- •Excessive alcohol or controlled drug use - More than 2 alcohol measures per day (one alcohol measure is a beer (250ml) or one glass of wine (125ml) or one strong measure (35ml) or one port/sherry (75ml)). Regular use of controlled drugs
- •Exclusion criterion for Hepatitis B naïve subjects (groups 1 and 2):
- •Previous vaccination with Hepatitis B vaccine
- •Exclusion criterion for non-responders (group 3):
- •Any Hepatitis B vaccination in the last 6 months
- •Temporary exclusion criterion for vaccination
- •Ear temperature > 38.4°C will lead to postponement of participation and vaccination. Screening may continue when the temperature has normalized.
研究组 & 干预措施
Non-responders - HBAI20
Subjects have been vaccinated 6 times with a Hepatitis B vaccine without developing a protective immune response, measured as anti Hepatitis B surface antigen antibodies, superior to 10mIU/ml.
Subjects are vaccinated with Hepatitis B vaccine HBAI20 at day 0 and 30, and Hepatitis B vaccine HBVaxPro-10ug at day 180.
干预措施: HBAI20 (Biological)
HB vaccine naive - HBAI20
Subjects have never been vaccinated with a Hepatitis B vaccine. Subjects are vaccinated with Hepatitis B vaccine HBAI20 at day 0 and 30, and Hepatitis B vaccine HBVaxPro-10ug at day 180.
干预措施: HBAI20 (Biological)
HB vaccine naive - HBVaxPro
Subjects have never been vaccinated with a Hepatitis B vaccine. Subjects are vaccinated with Hepatitis B vaccine HBVaxPro-10ug at day 0, 30, and 180.
干预措施: HBVaxPro (Biological)
结局指标
主要结局
Subjects With Local and/or General Adverse Events Irrespective of Severity
时间窗: Up to 7 months after first vaccination.
Subjects will be given a diary for 4 days after the first and second vaccination. Dairy: Local reactions at injection site: Pain (1 to 4), Impaired movement of injected arm (1 to 4), Redness/erythema (cm), Swelling (cm), Induration (cm) General/Systemic adverse events: Fever (temperature measurement), Headache (1 to 4), Fatigue (1 to 4), Muscle pain (1 to 4), Skin rash (1 to 4), Vomiting (1 to 4), Diarrhea (1 to 4). Record medication taken during the study (up to 7 months after the first vaccination).
Subjects With Local and/or General SEVERE Adverse Events
时间窗: Up to 7 months after first vaccination
Subjects will be given a diary for 4 days after the first and second vaccination. Dairy: Local reactions at injection site: Pain (1 to 4), Impaired movement of injected arm (1 to 4), Redness/erythema (cm), Swelling (cm), Induration (cm) General/Systemic adverse events: Fever (temperature measurement), Headache (1 to 4), Fatigue (1 to 4), Muscle pain (1 to 4), Skin rash (1 to 4), Vomiting (1 to 4), Diarrhea (1 to 4). Record medication taken during the study (up to 7 months after the first vaccination). The laboratory parameters analysed at day 10, 30, 40, 60, 180, and 210 are: Hematology: Hematocrit, Hemoglobin, RBC count, WBC count, Platelet count, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes. Biochemistry: Creatinine, Albumin, Alkaline Phosphatase, Total Bilirubin, ALT (GPT), AST (GOT), Gamma-Gt, C-Reactive Protein, and TSH/FT4. Urinalysis (day 10, 40, and 210): Clarity, Color, Specific gravity, Leukocytes, Nitrite, pH, Erythrocytes, Albumin, and Glucose.
次要结局
- Number of Participants With Seroprotection(Day 0, 10, 30, 40, 60, 180, and 210)