Phase I Clinical Trial in Healthy Female Volunteers of Reactogenicity and Immunogenicity of Nine Vaginal Immunisations With HIV CN54gp140 Glycoprotein
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 23
- 试验地点
- 4
- 主要终点
- To determine the local and systemic safety of vaginal immunisation with CN54gp140 glycoprotein administered 9 times over a 3 week period.
研究概览
简要总结
To determine the local (cervico-vaginal) and systemic (whole body) safety of vaginal immunisation with CN54gp140 glycoprotein administered 9 times over a 3 week period.
详细描述
This randomised, placebo-controlled, double-blind study will primarily assess the local and systemic safety and tolerability of CN54gp140 vaccine. We will also assess whether CN54gp140 vaccine is effective at inducing systemic and/or local specific immune responses.
Thirty healthy women volunteers will be enrolled in this study, at 2 clinical sites. Twenty will receive active CN54gp140 vaccine, and 10 will receive placebo. The placebo group will help us identify side effects caused by CN54gp140. The study is double-blind to eliminate any possibility of researcher or subject bias.
Before administration, CN54gp140 or placebo will be mixed into an aqueous gel vehicle. The treatments will be administered intravaginally in a regimen of 9 immunisations over 3 weeks. Each immunisation of CN54gp140 vaccine will contain 100 µg of CN54gp140 protein, meaning that a total dose of 900 µg will be given to subjects in the active treatment group.
Subjects will be required to make a total of 15 outpatient visits to their local clinical site, over 4 successive menstrual cycles.
Menstrual cycle 1: Screening visits There will be 2 screening visits, at about 4 and 2 weeks before the first immunisation. During these visits the volunteers will be asked questions about their health history and to give permission for us to contact their General Practitioner. Blood and urine samples will be taken for routine laboratory safety tests, and tests for HIV and hepatitis, sexual health, and pregnancy. Blood will also be collected for immunology tests to establish the pre-immunisation state of the immune system. The volunteers will also have a cervico-vaginal examination, and sampling of cervico-vaginal secretions and cells will be done for immunology tests. A photograph of the cervix will be taken to help identify any changes that might occur during the trial. Also, a full medical history and examination will be done.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •They are adult female volunteers, 18 to 45 years of age, who have signed an informed consent form following a detailed written explanation of participation in the protocol.
- •They are volunteers who are in good health as determined by medical history, physical examination and clinical judgement.
- •They are available for the duration of the study.
- •They are women who, if capable of becoming pregnant during the study, have agreed to have a pregnancy test immediately before immunisation, and to use appropriate contraception methods during the whole study period. Appropriate contraception shall include physician-prescribed oral hormonal agents, barrier contraceptives, regular and consistent use of condoms without spermicidal agents, or intrauterine devices only. Progesterone-only contraceptives are not suitable due to the lack of a regular menstrual cycle.
- •They have agreed not to undertake any vaginal practices other than receptive intercourse with a male or use of sanitary tampons during menses. Use of condoms without spermicidal agents is encouraged.
- •They have not donated blood during 3 months prior to study entry and agree to not donate for 3 months after the end of their participation in the study.
排除标准
- •They have hypersensitivity to any component of the vaccine used in this study.
- •They are found to be HIV antibody or HIV proviral DNA positive at the time of initial screening.
- •They have a known or suspected history of cervico-vaginal disease, malignancy or abnormality discovered at time of screening.
- •They present in the samples obtained at the screening visit:
- •a clinically significant amount of protein or haemoglobin in the urine sample, determined by urine dipstick.
- •a clinically significant abnormality in the haematological or biochemical assays.
- •Positive tests for Hepatitis B and/or C infection An abnormal value will be defined by the ranges quoted by The Doctors Laboratory for the Vaccine Institute site and Pathology Department, York Hospital for the York site.
- •They have a known or suspected impairment of lung, heart, liver, kidney, diseases, blood disorders or immune dysfunction.
- •They are receiving immunosuppressive therapy (including systemic steroids).
- •They are receiving any medications via vaginal route.
- •They have any acute infections (including fever greater than or equal to 38°C) or any chronic disease.
- •They present a current problem with substance abuse or with a history of substance abuse which, in the opinion of the investigator, might interfere with participation in the study.
- •They have any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.
- •They have received an investigational agent within 3 months prior to study entry.
- •They cannot speak fluent English, or are planning to leave the area of the study site prior to the end of the study period, or are likely not to complete the study.
结局指标
主要结局
To determine the local and systemic safety of vaginal immunisation with CN54gp140 glycoprotein administered 9 times over a 3 week period.
时间窗: 13 weeks
次要结局
- frequency of subjects mounting a cervico-vaginal IgA and IgG response to gp140 after a cycle of 9 vaginal immunisations(13 wks)
- frequency of subjects mounting a serum IgG and IgA response to gp140 after a cycle of 9 vaginal immunisations(13 wks)
- frequency of subjects with a T-cell response to gp140 in blood after a cycle of 9 vaginal immunisations(13 wks)
- frequency of cellular responses to gp140 in cervical cells after a cycle of 9 vaginal immunisations(13 wks)