Reactogenicity and Immunogenicity of Cervico-vaginal CN54gp140-hsp70 Conjugate Vaccine
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): CN54gp140 glycoprotein-hsp70 conjugate vaccine
Intervention type(s): Biological
Intervention description(s): CN54gp140-hsp70 conjugate vaccine administered intravaginally 3 times over a 12-week period
Other intervention name(s): ZM96gp140 glycoprotein
Intervention MeSH terms: polysaccharide-K
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: HIV Infections; Acquired Immune Deficiency Syndrome