A Phase I, Randomized, Double-blind, Placebo-controlled, Multi-centre, Ascending-dose Trial to Evaluate the Safety, Tolerability and Immunogenicity of Vaccine FP-02.2 in HBeAg-negative Hepatitis B Patients as an add-on Treatment to Entecavir or Tenofovir.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 21
- 主要终点
- Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
This study evaluates the safety and immunogenicity of FP-02.2, a new therapeutic Hepatitis B vaccine, administered as an add-on therapy to entecavir or tenofovir.
详细描述
This study evaluates the safety and immunogenicity of FP-02.2, a new therapeutic Hepatitis B vaccine, administered as an add-on therapy to entecavir or tenofovir. HBeAg-negative subjects will be randomized to receive low or high dose vaccine, in the presence or absence of IC31® adjuvant, or to receive placebo or IC31® adjuvant alone.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female subjects aged 18-65 years.
- •Diagnosed with chronic hepatitis B defined as HBsAg positive for at least 24 months.
- •Subject has received entecavir or tenofovir for at least 2 years with a stable dose for at least 6 months prior to screening.
- •HBeAg negative for at least 2 years prior to inclusion in the study.
- •HBV DNA <50 IU/mL for ≥ 12 months
- •ALT/AST ≤ 1.5 x ULN via the local laboratory at the Screening Visit
- •Able to give written informed consent to participate
- •Females should fulfil one of the following criteria:
- •At least one year menopausal
- •Surgically sterile
- •Same-sex relationship
- •WOCBP not surgically sterilized or with laboratory confirmed menopausal status are required to use a highly effective contraceptive measure with low used dependency from screening until one menstrual cycle after the last dose of IMP (Day 58) such as:
- •Combined (oestrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation
- •Progestogen-only hormonal contraception implants associated with inhibition of ovulation
- •Intrauterine device (IUD)
- •Intrauterine hormone-releasing system (IUS)
- •Bilateral tubal occlusion
- •Vasectomised partner - must have had medical assessment of successful surgery.
- •From screening until one menstrual cycle after the last dose of IMP (day 57).
- •Subjects who practice true abstinence or who exclusively have same sex partners need not use contraception, provided it is in line with their preferred and usual lifestyle. Periodic abstinence (eg calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Should any such subject stop practicing true abstinence, they must use contraception as described above.
- •Males should fulfil one of the following criteria:
- •Surgically sterile
- •Willing to abstain from sexual intercourse or use a reliable form of contraception (e.g. condom), if having sex with a pregnant or non-pregnant woman of childbearing potential, from screening until 3 months after the final dose of IMP.
- •Surgically sterilised or post-menopausal female partner or same-sex relationship.
排除标准
- •Liver disease other than chronic hepatitis B (a diagnosis of steatosis is permitted providing inclusion criterion 6 is met).
- •Evidence of Liver cirrhosis on Fibroscan screening (Liver cirrhosis is defined as a Fibroscan measurement of >11.5 KPa), or previous history or evidence of cirrhosis on radiological imaging, Fibroscan or liver biopsy.
- •Positive serology for HIV-1 or HIV-2 or HCV or HDV antibodies.
- •Immunodeficient or autoimmune conditions due to disease or medication e.g. systemic steroids within previous 12 weeks. (Topical or inhaled steroids are permissible).
- •Clinically relevant co-morbidity, e.g. autoimmune disease.
- •Clinically relevant anaemia or leukopenia in the opinion of the investigator.
- •Cancer or treatment for cancer within 3 years prior to screening excluding basal cell carcinoma of the skin, which is allowed.
- •Known or suspected intolerance or hypersensitivity to the IMP or closely related compounds or any of the stated ingredients.
- •Receipt of any IMP within 90 days prior to screening or currently receiving IMP or intent to receive IMP.
- •Current substance or alcohol abuse that in the opinion of the Investigator would interfere with compliance or with interpretation of study results.
- •Any condition that in the opinion of the Investigator might interfere with study objectives.
- •Pregnant or breastfeeding.
- •Subjects should not have received, during the 6 month period prior to screening, any medications or other treatments that may adversely affect the immune system such as allergy injections, immunoglobulins, interferons, cytotoxic drugs or other drugs known to be frequently associated with significant major organ toxicity, or systemic corticosteroids (oral or injectable).
- •Immunosuppressive treatment such as azathioprine or mercaptopurine is not permitted 6 months prior to screening.
- •Administration of live vaccines (such as live influenza vaccinations or live travel vaccinations) from 10 days prior to the screening visit until Day 85.
研究组 & 干预措施
FP-02.2 Low Dose
A low dose (150 µg/peptide) of the FP-02.2 vaccine administered by IM injection on Days 1, 29, and 57.
干预措施: FP-02.2 Vaccine (Biological)
FP-02.2 High Dose
A high dose (500 µg/peptide) of the FP-02.2 vaccine administered by IM injection on Days 1, 29, and 57.
干预措施: FP-02.2 Vaccine (Biological)
FP-02.2 Low Dose with IC31® Adjuvant
A low dose (150 µg/peptide) of the FP-02.2 vaccine with IC31® Adjuvant administered by IM injection on Days 1, 29, and 57.
干预措施: FP-02.2 Vaccine (Biological)
FP-02.2 Low Dose with IC31® Adjuvant
A low dose (150 µg/peptide) of the FP-02.2 vaccine with IC31® Adjuvant administered by IM injection on Days 1, 29, and 57.
干预措施: IC31® Adjuvant (Other)
FP-02.2 High Dose with IC31® Adjuvant
A high dose (500 µg/peptide) of the FP-02.2 vaccine with IC31® Adjuvant administered by IM injection on Days 1, 29, and 57.
干预措施: FP-02.2 Vaccine (Biological)
FP-02.2 High Dose with IC31® Adjuvant
A high dose (500 µg/peptide) of the FP-02.2 vaccine with IC31® Adjuvant administered by IM injection on Days 1, 29, and 57.
干预措施: IC31® Adjuvant (Other)
Placebo
Placebo administered by IM injection on Days 1, 29, and 57.
干预措施: Placebo (Other)
IC31® Adjuvant
IC31® Adjuvant alone administered by IM injection on Days 1, 29, and 57.
干预措施: IC31® Adjuvant (Other)
结局指标
主要结局
Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
时间窗: Throughout the study to Day 85
Incidences of all TEAEs, IP related TEAEs, severe TEAEs, TEAEs leading to discontinuation of IP, and serious TEAEs,
Number of Subjects With Local Injection Site Reactions
时间窗: Days 1 through 64
Incidence of local injection site reactions occurring up to 7 days after each injection
次要结局
- Immunological Response(Change from baseline to Day 85)