A Dose Escalation Phase I Trial of the Safety and Immunogenicity of RG1-VLP, A Candidate Broadly Protective Vaccine for the Prevention of HPV-Associated Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 10
- 主要终点
- Incidence of adverse events
研究概览
简要总结
This phase I trial tests the safety, side effects, and best dose of RG1-virus-like particle (VLP) in preventing human papillomavirus (HPV)-related cancers in women. RG1-VLP is a vaccine that aims to protect against rare HPV types not targeted by currently approved HPV vaccines. HPV is a common sexually-transmitted infection that can cause certain genital and oral cancers. RG1-VLP contains a protein of HPV type 16 (HPV16) with a slightly different structure than the licensed Gardasil-9 vaccine. Gardasil-9 is approved by the Federal Drug Administration to help protect against diseases caused by some types of HPV. Gardasil-9 also contains 9 different HPV proteins. Both vaccines contain alum to stimulate the immune system. The usual approach for the prevention of HPV-related cancers for patients who are at increased risk is to consider the currently approved HPV vaccine like Gardasil-9, as well as to be followed closely by their doctor to watch for the development of cancer via routine pap smears. This trial may allow researchers to find out whether the RG1-VLP vaccine can safely trigger an immune response against HPV in healthy women and if it is better or worse than the usual approach for the prevention of HPV-related cancers.
详细描述
PRIMARY OBJECTIVE:
I. Assess the safety of RG1-virus-like particles (VLP) in healthy 18-60 years old women at 3 escalating doses.
SECONDARY OBJECTIVES:
I. Determine the immunogenicity of RG1-VLP in healthy 18-60 year old women at 3 escalating doses via the following assays:
Ia. Determine serum antibody responses induced by RG1-VLP vaccination by both human papillomavirus (HPV) 16 L1 VLP and HPV16 L2 RG1-peptide enzyme-linked immunosorbent assay (ELISA). This will be assessed at months 0, 1, 2, 3, 6, 7 and 12; Ib. Determine whether vaccination-induced serum antibody response neutralizes HPV16. This will be assessed at months 0, 1, 2, 3, 6, 7 and 12.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- None (Participant, 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
- 是
入选标准
- •Women, age 18 - 60 years. Because no dosing or adverse event (AE) data is currently available for the use of RG1-VLP in humans, children and adolescents are excluded from this study
- •White blood cell (WBC) between 3000/mm^3 - institutional upper limit of normal
- •Hemoglobin (Hgb) between 10 g/dl - institutional upper limit of normal
- •Platelets >= 100,000/mm^3
- •Serum creatinine within institutional normal limits
- •Bilirubin =< 2x institutional upper limit of normal
- •Alanine aminotransferase (ALT) =< 2x institutional upper limit of normal
- •Aspartate aminotransferase (AST) =< 2x institutional upper limit of normal
- •Human immunodeficiency virus (HIV)-1/HIV-2 negative
- •Hepatitis B and hepatitis C negative
- •The effects of RG1-VLP vaccination on the developing human fetus at the proposed doses are unknown. For this reason, all women of childbearing potential will have a pregnancy test and all heterosexually active women must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately. The following persons are not considered to be able to bear children and are therefore eligible to participate without the use of concurrent birth control:
- •Female with bilateral oophorectomy and/or hysterectomy
- •Female with fallopian tubes cut, tied or sealed
- •Female with sterilization implant (e.g. Adiana, Essure) placed > 3 months prior to registration
- •Female post-menopausal (> 1 year since last menses or prior laboratory follicle stimulating hormone (FSH) value per institutional range indicating post- menopausal)
- •Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •History of any of the following:
- •Prior or current genital warts
- •Treatment for anogenital intraepithelial neoplasia (cervical intraepithelial neoplasia [CIN], anal intraepithelial neoplasia [AIN], vaginal intraepithelial neoplasia [VAIN], vulvar intraepithelial neoplasia [VIN])
- •Systemic cancer treatment within the prior year
- •History of anaphylaxis to vaccines
- •Any prior vaccination with Gardasil, Gardasil-9, or Cervarix or other HPV vaccine
- •Receipt of blood products within 3 months of enrollment, or continuing plasma donation
- •Participants receiving any other investigational agents
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to the adjuvant or to RG1-VLP
- •Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements or preclude protocol vaccination
- •Pregnant women or actively lactating women are excluded from this study because RG1-VLP is a vaccine with the potential for teratogenic or abortifacient effects
- •Planned receipt of any inactivated vaccine in the 2 weeks preceding and the 2 weeks following any trial vaccination
- •Planned receipt of any live attenuated vaccine in the 4 weeks preceding and the 4 weeks following any trial vaccination
- •Women with a history of bleeding disorders or use of anticoagulants (aspirin is acceptable)
- •Had prior medical diagnoses:
- •Rheumatoid arthritis or other auto-immune disease
- •Congenital or acquired immunodeficiency
- •Collagen vascular disease
- •Following medical treatments:
- •Current use of immunosuppressive drugs including corticosteroid use (inhaled or topical steroids are permitted)
- •Unrecovered major infections and/or surgical procedures
研究组 & 干预措施
Prevention (RG1-VLP, Gardasil-9)
Patients receive RG1-VLP IM for 3 doses at months 0, 2, and 6 in the absence of unacceptable toxicity. Patients may also receive Gardasil-9 via injection for 3 doses at 6 months after the 3rd study vaccination (month 12), then at months 14 and 18 in the absence of unacceptable toxicity. Patients also undergo blood sample collection on study and may undergo vaginal swab collection on study.
干预措施: Recombinant Human Papillomavirus Nonavalent Vaccine (Biological)
Prevention (RG1-VLP, Gardasil-9)
Patients receive RG1-VLP IM for 3 doses at months 0, 2, and 6 in the absence of unacceptable toxicity. Patients may also receive Gardasil-9 via injection for 3 doses at 6 months after the 3rd study vaccination (month 12), then at months 14 and 18 in the absence of unacceptable toxicity. Patients also undergo blood sample collection on study and may undergo vaginal swab collection on study.
干预措施: Questionnaire Administration (Other)
Prevention (RG1-VLP, Gardasil-9)
Patients receive RG1-VLP IM for 3 doses at months 0, 2, and 6 in the absence of unacceptable toxicity. Patients may also receive Gardasil-9 via injection for 3 doses at 6 months after the 3rd study vaccination (month 12), then at months 14 and 18 in the absence of unacceptable toxicity. Patients also undergo blood sample collection on study and may undergo vaginal swab collection on study.
干预措施: Biospecimen Collection (Procedure)
Prevention (RG1-VLP, Gardasil-9)
Patients receive RG1-VLP IM for 3 doses at months 0, 2, and 6 in the absence of unacceptable toxicity. Patients may also receive Gardasil-9 via injection for 3 doses at 6 months after the 3rd study vaccination (month 12), then at months 14 and 18 in the absence of unacceptable toxicity. Patients also undergo blood sample collection on study and may undergo vaginal swab collection on study.
干预措施: HPV16 RG1 VLP Vaccine (Biological)
结局指标
主要结局
Incidence of adverse events
时间窗: Up to 6 months post-3rd RG1-virus-like particle (VLP) vaccination/saline injection
Safety of the three escalating doses of RG1-VLP will be assessed by adverse events in terms of severity grade and attribution to vaccination as ordinal outcomes. All toxicities will be tabulated and frequencies and percentages of events will be presented for each vaccine dose cohort. The severity of the adverse events will be assessed using the Common Terminology Criteria for Adverse Events 5.0 and supplemented by Food and Drug Administration "Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials."
次要结局
- Determination of serum antibody responses to both human papillomavirus (HPV)16 L1 VLP and to HPV16 L2(At months 0, 1, 2, 3, 6, 7, and 12)
- Determination of whether vaccination-induced serum antibody response neutralizes HPV16(At months 0, 1, 2, 3, 6, 7, and 12)