A Phase 1b/2, Randomised, Placebo-controlled, Dose-ranging Study to Evaluate Safety, Tolerability and Immunogenicity of a Chimpanzee Adenovirus (ChAdOx1)-Vectored Multigenotype High Risk Human Papillomavirus (hrHPV) Vaccine and Modified Vaccinia Ankara (MVA)-Vectored Multigenotype hrHPV Vaccine in Women With Low-grade HPV-related Cervical Lesions
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 108
- 试验地点
- 16
- 主要终点
- Incidence of adverse events to measure safety and reactogenicity
研究概览
简要总结
A Phase 1b/2 multi-centre study evaluating the safety, efficacy and immunogenicity of prime-boost vaccines ChAdOx1-HPV and MVA-HPV in women with HPV related low grade cervical lesions.
详细描述
The study consists of an open label, non-randomised, dose escalation Lead in phase. 9 participants with high-risk HPV, in cohorts of 3 in 3 dose ascending groups, will be vaccinated after SMC safety data reviews.
This is followed by a blinded, randomised Main phase with 96 participants with high-risk HPV, in parallel running dose cohorts (three different doses of ChAdOx1-HPV plus two different doses of MVA-HPV versus placebo plus placebo boost). At least 60 of these participants will take part in the immunogenicity sub-study.
A blinded, randomised expansion phase investigating the effects of up to two different main phase doses against placebo will be further defined prior to commencing this phase of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Lead in phase will be open label. Main phase and expansion phase will be blinded.
入排标准
- 年龄范围
- 25 Years 至 55 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Females aged ≥25 and ≤55 years of age at screening.
- •Persistent hrHPV infection defined as a documented cervical infection with hrHPV type(s) in the 6 to 18 months prior to screening and confirmed at screening (participants in the main and expansion phases only). Participants in the lead-in phase are only required to have the screening result.
- •Low- grade cervical lesion (CIN1 or HPV-related change only) confirmed by histology and/or cytology report within the 1 year prior to screening.
- •Not pregnant or breast feeding and one of the following:
- •Of non-childbearing potential (i.e. women who have had a hysterectomy or tubal ligation or are postmenopausal, as defined by no menses for at least 12 months and without an alternative medical cause)
- •Of childbearing potential but agrees to practice highly effective contraception for 4 weeks prior to administration of the first dose of study vaccine and throughout the study until 8 weeks after administration of the second dose. Highly effective methods of contraception include one or more of the following:
- •Male partner who is sterile (medically effective vasectomy) prior to the female participant's entry into the study and is the sole sexual partner for the female participant
- •Hormonal (oral, intravaginal, transdermal, implantable or injectable). Progestogen-only hormonal contraceptives without inhibition of ovulation are not considered to be highly effective.
- •An intrauterine hormone releasing system
- •An intrauterine device
- •Bilateral tubal occlusion
- •Sexual abstinence, only if the participant refrains from heterosexual intercourse during the entire study period and it is the usual lifestyle of the participant
- •Willing to abstain from sexual activity for 48 hours prior to all swabbing procedures
排除标准
- •Presence of any significant acute or chronic, uncontrolled medical (or psychiatric) illness, including blood dyscrasias.
- •Immunosuppression as a result of underlying illness or treatment including:
- •Use of high dose corticosteroids ( >10 mg/day prednisone or equivalent) for ≥7 days (inhaled, otic and ophthalmic corticosteroids are permitted)
- •Primary immune deficiency disease
- •Use of synthetic or biologic disease-modifying antirheumatic drugs
- •History of bone marrow or solid organ transplant
- •History of any other clinically significant autoimmune or immunosuppressive disease
- •Positive diagnostic tests (for human immunodeficiency virus, hepatitis B or hepatitis C) indicating chronic infection.
- •Evidence of high grade cervical lesions by colposcopy or by Papanicolaou (Pap) smear test in the 1 year prior to screening.
- •Any history of anaphylaxis in reaction to vaccination or history of allergic reactions likely to be exacerbated by any component of the vaccine, e.g. severe allergy to eggs.
- •Receipt of any investigational drug or investigational vaccine within 3 months prior to administration of ChAdOx1-HPV on Day 0, or prior participation in a clinical study of any HPV vaccine.
- •Receipt of any adenoviral based vaccine within 3 months prior to administration of ChAdOx1 HPV on Day 0, or plan to receive an adenoviral-based vaccine within 3 months after Day
- •Receipt of any live vaccines within the 30 days or inactivated vaccine within the 14 days prior to administration of ChAdOx1-HPV on Day 0 or planned to occur in the 2 months after the Day 0 vaccination.
- •Current or history of illicit drug use within the 6 months prior to screening.
- •Current or history of severe alcohol abuse within the 6 months prior to screening.
- •Any laboratory test which is abnormal and deemed by the Investigator to be clinically significant which will potentially affect the participation in the study.
- •Current known infection with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2)
- •Any other finding that, in the opinion of the Investigator, deems the participant unsuitable for the study.
研究组 & 干预措施
Group 6 Placebo Saline
Sodium Chloride (0.9%)
干预措施: Placebo (Biological)
Lead-in Group A ChAdOx1-HPV low dose and MVA-HPV low dose
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^8 vp) and MVA-HPV (1 x 10^7 pfu)
干预措施: ChAdOx1-HPV (Biological)
Lead-in Group A ChAdOx1-HPV low dose and MVA-HPV low dose
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^8 vp) and MVA-HPV (1 x 10^7 pfu)
干预措施: MVA-HPV (Biological)
Lead-in Group B ChAdOx1-HPV mid dose and MVA-HPV low dose
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^9 vp) and MVA-HPV (1 x 10^7 pfu)
干预措施: ChAdOx1-HPV (Biological)
Lead-in Group B ChAdOx1-HPV mid dose and MVA-HPV low dose
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^9 vp) and MVA-HPV (1 x 10^7 pfu)
干预措施: MVA-HPV (Biological)
Lead-in Group C ChAdOx1-HPV high dose and MVA-HPV high dose
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^10) vp and MVA-HPV (1 x 10^8 pfu)
干预措施: ChAdOx1-HPV (Biological)
Lead-in Group C ChAdOx1-HPV high dose and MVA-HPV high dose
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^10) vp and MVA-HPV (1 x 10^8 pfu)
干预措施: MVA-HPV (Biological)
Group 1 ChAdOx1-HPV mid dose and MVA-HPV low dose
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^9 vp) and MVA-HPV (1 x 10^7 pfu)
干预措施: ChAdOx1-HPV (Biological)
Group 1 ChAdOx1-HPV mid dose and MVA-HPV low dose
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^9 vp) and MVA-HPV (1 x 10^7 pfu)
干预措施: MVA-HPV (Biological)
Group 2 ChAdOx1-HPV high dose and MVA-HPV low dose
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^10 vp) and MVA-HPV (1 x 10^7 pfu)
干预措施: ChAdOx1-HPV (Biological)
Group 2 ChAdOx1-HPV high dose and MVA-HPV low dose
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^10 vp) and MVA-HPV (1 x 10^7 pfu)
干预措施: MVA-HPV (Biological)
Group 3 ChAdOx1-HPV low dose and MVA-HPV high dose
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^8 vp) and MVA-HPV (1 x 10^8 pfu)
干预措施: ChAdOx1-HPV (Biological)
Group 3 ChAdOx1-HPV low dose and MVA-HPV high dose
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^8 vp) and MVA-HPV (1 x 10^8 pfu)
干预措施: MVA-HPV (Biological)
Group 4 ChAdOx1-HPV mid dose and MVA-HPV high dose
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^9 vp) and MVA-HPV (1 x 10^8 pfu)
干预措施: ChAdOx1-HPV (Biological)
Group 4 ChAdOx1-HPV mid dose and MVA-HPV high dose
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^9 vp) and MVA-HPV (1 x 10^8 pfu)
干预措施: MVA-HPV (Biological)
Group 5 ChAdOx1-HPV high dose and MVA-HPV high dose
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^10 vp) and MVA-HPV (1 x 10^8 pfu)
干预措施: ChAdOx1-HPV (Biological)
Group 5 ChAdOx1-HPV high dose and MVA-HPV high dose
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^10 vp) and MVA-HPV (1 x 10^8 pfu)
干预措施: MVA-HPV (Biological)
结局指标
主要结局
Incidence of adverse events to measure safety and reactogenicity
时间窗: 3 months for the lead-in and 12 months for the main phase
Measure of adverse events, serious adverse events (SAEs), ≥Grade 3 study vaccine-related adverse events reported.
次要结局
- Determine the effect of ChAdOx1-HPV plus MVA-HPV vaccines on cervical intraepithelial neoplasia (CIN)(12 months for main phase only)
- Determine the dose of ChAdOx1-HPV plus MVA-HPV vaccines for further development(3 months for lead in phase and 12 months for main phase)
- Determine the effect of ChAdOx1-HPV plus MVA-HPV vaccines on the clearance of high risk HPV infection(12 months for main phase only)