Reactogenicity and Immunogenicity of Cervico-vaginal CN54gp140-hsp70 Conjugate Vaccine (TL01)
A vaccine to prevent infection with the Human Immunodeficiency Virus (HIV) is urgently needed. Worldwide, most HIV infections occur through sex between a man and woman. The vaccine in this study consists of a protein from HIV that has been synthetically produced and linked to a protein that boosts immune responses. It has not been tested in humans before, but it is expected (from animal studies) that direct application into the female genital tract (via the vagina) as liquid drops, will provoke immune protection at the site of HIV infection. This is less applicable to men, therefore only healthy, HIV negative women will be recruited. The investigators will recruit at one site, which is a university vaccine research centre with experience of running similar trials. The study will last 24 weeks during which subjects will have blood samples taken on six visits, and three immunisations over 12 weeks in which 1 millilitres of vaccine is placed into the vaginal by inserting a small plastic syringe. The purpose of this initial small study is to monitor safety of the vaccine and to determine whether it is appropriate to continue into future, larger studies in which the immune response to the vaccine is measured.
Biological: CN54gp140 glycoprotein-hsp70 conjugate vaccine
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||Phase I Clinical Trial in Healthy Female Volunteers of Reactogenicity and Immunogenicity of Three Cervico-vaginal Topical Immunisations With a Fixed Dose of HIV CN54gp140 Glycoprotein-hsp70 Conjugate Vaccine|
- Frequency of local immunisation site vaccine-related Adverse Events [ Time Frame: 20 weeks ] [ Designated as safety issue: Yes ]Semi-structured diary card of solicited local symptoms (vaginal irritation, discharge, bleeding), investigator-prompted recall of unsolicited symptoms, recorded for 20 weeks from day of first immunisation. Visual inspection of cervix-vagina by trained operator prior to immunisation and on final visit.
- Frequency of generalised vaccine-related Adverse Events [ Time Frame: 20 ] [ Designated as safety issue: Yes ]Semi-structured diary card of solicited generalised symptoms (headache, fever, malaise, chills, myalgia), investigator-prompted recall of unsolicited symptoms, recorded for 20 weeks from day of first immunisation.
- Frequency of vaccine-related Adverse Events in hematology and serum biochemistry parameters [ Time Frame: 20 ] [ Designated as safety issue: Yes ]Adverse Events defined as deviation from normal ranges defined for pre-determined panels of hematology and serum biochemistry parameters.
- Frequency of subjects mounting a cervico-vaginal antibody response to CN54gp140 [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]Exploratory assay of cervico-vaginal antibody to CN54gp140, measured at each scheduled study visit. Not a study endpoint.
- Frequency of subjects mounting a cervico-vaginal antibody response to hsp70 [ Time Frame: 20 weeks ] [ Designated as safety issue: Yes ]Exploratory assay of cervico-vaginal antibody to hsp70, measured at each scheduled study visit. Not a study endpoint.
- Frequency of subjects mounting a T cellular proliferative response to CN54gp140 [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]Exploratory assay of T cell proliferation in response to in vitro antigen stimulation, measured at each scheduled study visit. Not a study endpoint.
- Frequency of subjects mounting a serum antibody response to CN54gp140 [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]Exploratory assay of serum antibody to CN54gp140, measured at each scheduled study visit. Not a study endpoint.
- Frequency of subjects mounting a serum antibody response to hsp70 [ Time Frame: 20 weeks ] [ Designated as safety issue: Yes ]Exploratory assay of serum antibody to hsp70, measured at each scheduled study visit. Not a study endpoint.
|Study Start Date:||July 2011|
|Study Completion Date:||December 2012|
|Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
Experimental: Vaginal immunisation
CN54gp140 glycoprotein-hsp70 conjugate vaccine
Biological: CN54gp140 glycoprotein-hsp70 conjugate vaccine
CN54gp140-hsp70 conjugate vaccine administered intravaginally 3 times over a 12-week period
Other Name: ZM96gp140 glycoprotein
This hypothesis-generating, first-in-human, Phase 1 study will be conducted according to the Standard Operating Procedures (SOPs) of St George's. The purpose of the study is to determine the immediate safety and reactogenicity of the vaccine, to guide future larger Phase 1/2 studies of safety and efficacy.
Eight subjects will be included to receive 3 cervico-vaginal topical applications of 100µg of CN54gp140-hsp70 conjugate vaccine in 1.0 mL physiological buffer, administered as topical intra-vaginal drops on day 0, and at 4 and 12 weeks after the first immunisation. The study will consist of 1 pre-study screening visit, 3 immunisation visits, and 2 follow-up visits over a total period of 20 weeks. Subjects will be recruited as one cohort in two groups of four. The dose of antigens and immunisation schedule has been selected based on pre-clinical and clinical experience with the same HIV envelope protein.
Each subject's medical history (including past and present illnesses, current medications, family medical history) will be formally assessed and recorded at screening. Volunteers' age, gender, height, weight and ethnic origin will be recorded. A full physical examination will be conducted by a registered medical practitioner at screening and the final study visit. Regular assessments of vital signs (pulse, blood pressure, temperature) will be made on all visits.
Diary cards, investigator-prompted recall of events, laboratory tests (haematology, biochemistry) and direct visualisation of immunisation site will be used to identify Adverse Events. Frequency of vaccine-related Adverse Events is the Primary Study Endpoint.
Before and after each immunisation visit (0, 4 and 12 weeks) blood samples will be obtained for collection of serum and for separation of PBMCs for cellular assays. At each time point, vaginal and cervical secretions will be taken. All immunology assays are exploratory and are not study endpoints. HIV serology and DNA detection will be repeated at the final visit to detect subjects who may have contracted HIV infection during the study period, and who may therefore have developed antibody and T-cell responses due to the HIV infection that would interfere with exploratory immunology assays.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01285141
|St George's - University of London|
|London, England, United Kingdom, SW17 0RE|
|Principal Investigator:||David JM Lewis, MD||St George's, University of London, UK|