A Randomized, Double-blind, Placebo-controlled, First-in-Human, Phase 1/2a Study to Evaluate Safety, Reactogenicity and Immunogenicity of Monovalent HPV16 and HPV18 Ad26-vectored Vaccine Components and an MVA-vectored HPV16/18 Vaccine Component in Otherwise Healthy Women With HPV16 or 18 Infection of the Cervix
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 12
- 主要终点
- Number of Participants With Solicited Local Adverse Events (AEs)
研究概览
简要总结
The main purpose of this study is to assess safety and reactogenicity of the 3 vaccine regimens.
详细描述
This study is part of a vaccine program which aims to generate a therapeutic vaccine for women with HPV types 16 or 18 infection, with a focus on early disease interception. The study consists of 3 periods: Screening period of up to 42 days (6 weeks), followed by prime and boost immunizations and follow-up visits up to 12 months after the first vaccination. Evaluation of the safety/reactogenicity of the vaccine regimens will include physical assessment by study-site personnel, participant reports on signs and symptoms and laboratory assessments following vaccinations. Immunogenicity and Virology/Histology assessments will also be performed.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Willing and able to adhere to the prohibitions and restrictions specified in this protocol
- •Must have an human papillomavirus (HPV) type 16 or 18 infection of the cervix as determined by a qualitative PCR test within 8 weeks prior to screening or at the time of screening. Available history of high-risk (HR)-HPV positivity and HPV16 or HPV18 positivity positivity will be recorded
- •Must have a recent colposcopy result (with a maximum of 12 months old at screening); in case a colposcopy has not been performed before, it will be done as screening procedure
- •Contraceptive (birth control) use by participants should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies
- •Agrees not to donate blood until 3 months after receiving the last dose of study vaccine
排除标准
- •In case cytology results are available, participant has current or history of high-grade squamous intraepithelial lesion (HSIL), adenocarcinoma in situ (AIS) or any high-grade vulvar, vaginal or anal intraepithelial neoplasia
- •Current or history of cervical intraepithelial neoplasia (CIN)2+ or cervical cancer
- •Confirmed co-infection with both HPV16 and HPV18
- •History of an underlying clinically significant acute or chronic medical condition, other than infection with HPV, or physical examination findings for which, in the opinion of the investigator, participation would not be in the best interest of the participant (for example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
- •Tests positive for human immunodeficiency virus (HIV) at screening
- •Chronic active hepatitis B or hepatitis C infection, verified at screening by hepatitis B surface antigen or anti-hepatitis C virus antibody, respectively
- •Vaginal atrophy with or without topical hormonal therapies or systemic selective estrogen receptor modulators
- •Exposed to at least 1 dose of an HPV prophylactic vaccine or participant has participated in the past in another preventive or therapeutic HPV vaccine study
- •Clinically significant gynecological abnormalities that could, in the judgment of the investigator, interfere with study evaluation (for example [e.g.], prolapse, myoma, fibroid, hysterectomy)
- •Symptomatic vaginal or genital infection (including genital herpes) as confirmed by physician or investigator
研究组 & 干预措施
Regimen 1: Single Ad26.HPV16 or Ad26.HPV18 and MVA.HPV16/18
Participants will receive a dose of adenovirus serotype 26 (Ad26)-human papillomavirus (HPV)16 or HPV18 (Ad26.HPV16 or Ad26.HPV18) as prime immunization and a dose of Modified Vaccinia Ankara (MVA)-HPV16/18 (MVA.HPV16/18) as boost immunization.
干预措施: Ad26.HPV16 (Biological)
Regimen 1: Single Ad26.HPV16 or Ad26.HPV18 and MVA.HPV16/18
Participants will receive a dose of adenovirus serotype 26 (Ad26)-human papillomavirus (HPV)16 or HPV18 (Ad26.HPV16 or Ad26.HPV18) as prime immunization and a dose of Modified Vaccinia Ankara (MVA)-HPV16/18 (MVA.HPV16/18) as boost immunization.
干预措施: Ad26.HPV18 (Biological)
Regimen 1: Single Ad26.HPV16 or Ad26.HPV18 and MVA.HPV16/18
Participants will receive a dose of adenovirus serotype 26 (Ad26)-human papillomavirus (HPV)16 or HPV18 (Ad26.HPV16 or Ad26.HPV18) as prime immunization and a dose of Modified Vaccinia Ankara (MVA)-HPV16/18 (MVA.HPV16/18) as boost immunization.
干预措施: MVA.HPV16/18 (Biological)
Regimen 2: Double Ad26.HPV16 or Ad26.HPV18 and MVA.HPV16/18
Participants will receive a double dose of Ad26.HPV16 or Ad26.HPV18 as prime immunization and a dose of MVA.HPV16/18 as boost immunization.
干预措施: Ad26.HPV16 (Biological)
Regimen 3: Ad26.HPV16/Ad26.HPV18 mix and MVA.HPV16/18
Participants will receive a mix of Ad26.HPV16/Ad26.HPV18 as prime immunization and a dose of MVA.HPV16/18 as boost immunization.
干预措施: MVA.HPV16/18 (Biological)
Regimen 2: Double Ad26.HPV16 or Ad26.HPV18 and MVA.HPV16/18
Participants will receive a double dose of Ad26.HPV16 or Ad26.HPV18 as prime immunization and a dose of MVA.HPV16/18 as boost immunization.
干预措施: Ad26.HPV18 (Biological)
Regimen 2: Double Ad26.HPV16 or Ad26.HPV18 and MVA.HPV16/18
Participants will receive a double dose of Ad26.HPV16 or Ad26.HPV18 as prime immunization and a dose of MVA.HPV16/18 as boost immunization.
干预措施: MVA.HPV16/18 (Biological)
Regimen 3: Ad26.HPV16/Ad26.HPV18 mix and MVA.HPV16/18
Participants will receive a mix of Ad26.HPV16/Ad26.HPV18 as prime immunization and a dose of MVA.HPV16/18 as boost immunization.
干预措施: Ad26.HPV16 (Biological)
Regimen 3: Ad26.HPV16/Ad26.HPV18 mix and MVA.HPV16/18
Participants will receive a mix of Ad26.HPV16/Ad26.HPV18 as prime immunization and a dose of MVA.HPV16/18 as boost immunization.
干预措施: Ad26.HPV18 (Biological)
Control: Placebo
Participants will receive matched placebo as prime and boost immunizations.
干预措施: Placebo (Biological)
结局指标
主要结局
Number of Participants With Solicited Local Adverse Events (AEs)
时间窗: Up to 7 days after each vaccination (Up to Day 64)
Number of participants with solicited local AEs were reported. Solicited local AE's included pain/tenderness, erythema, and induration/swelling.
Number of Participants With Solicited Systemic AEs
时间窗: Up to 7 days after each vaccination (Up to Day 64)
Number of participants with solicited systemic AEs were reported. Solicited systemic AEs included headache, fatigue, myalgia, arthralgia, chills, and fever.
Number of Participants With Unsolicited AEs
时间窗: 28 days after each vaccination (Up to Day 85)
Number of participants with unsolicited AEs were reported. Unsolicited AEs included all AEs for which the participant was not specifically questioned in the participant diary.
Number of Participants With Serious Adverse Events (SAEs)
时间窗: Up to 12 months after the first vaccination (target visit Day 366)
Number of participants with SAEs were reported. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
次要结局
- Percentage of Participants With Human Papillomavirus (HPV)-Specific CD4+ T-cell Responses: Interferon (IFN)g+(Day 57, Day 78, Day 239, and Day 366)
- Percentage of Participants With HPV-Specific CD4+ T-cell Responses: Interleukin (IL)2+(Day 57, Day 78, Day 239, and Day 366)
- Percentage of Participants With HPV-Specific CD4+ T-cell Responses: Tumor Necrosis Factor (TNF)a+(Day 57, Day 78, Day 239, and Day 366)
- Percentage of Participants With HPV-Specific CD8+ T-cell Responses: IFNg+(Day 57, Day 78, Day 239, and Day 366)
- Percentage of Participants With HPV-Specific CD8+ T-cell Responses: IL2+(Day 57, Day 78, Day 239, and Day 366)
- Percentage of Participants With HPV-Specific CD8+ T-cell Responses: TNFa+(Day 57, Day 78, Day 239, and Day 366)