Safety and Immunogenicity of MVA.HIVconsv in HIV-1 Seropositive Adults on HAART
- Conditions
- HIV-1
- Registration Number
- NCT01024842
- Lead Sponsor
- University of Oxford
- Brief Summary
In this study, the novel vaccine candidate, MVA.HIVconsv, will be tested for safety, tolerability and immunogenicity in HIV-1-seropositive subjects receiving effective antiretroviral therapy.
MVA.HIVconsv will be tested as a single vaccine modality, as a prelude to testing in a heterologous viral vector boost regimen which will include a replication-defective simian adenovirus expressing the same immunogen.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 19
-
Male or female, aged 18-60 years
-
Confirmed HIV-1 seropositive
-
Willing and able to give written informed consent for participation in the study
-
Treated continuously with a combination of 3 or more antiretroviral agents for the preceding 12 months
-
Willing and able to adhere to an effective ART regimen for the duration of the study (switching from current regimen is allowed if for reasons of tolerability or toxicity)
-
CD4 cell count > 350 cells/μl at screening and at the preceding clinic visit
-
Plasma viral load < 50 copies / ml at screening and at the preceding clinic visit
-
No new AIDS-defining diagnosis or progression of HIV-related disease in the preceding 6/12 months
-
Haematological and biochemical laboratory parameters as follows:
- Haemoglobin > 10g/dl
- Platelets > 100,000/μl
- ALT ≤ 2.5 x ULN
- Creatinine ≤ 1.3 x ULN
-
Serology: negative for hepatitis B surface antigen OR HbsAg positive with HBV DNA < 1000 copies/ml; negative for hepatitis C antibodies OR confirmed clearance of HCV infection (spontaneous or following treatment); negative syphilis serology or documented adequate treatment of syphilis if positive EIA IgG or TPHA
-
Available for follow up for duration of study (screening + 38 weeks) and willing to comply with the protocol requirements
-
Women of child-bearing age must not be pregnant, planning a pregnancy or breast-feeding. Sexually active women must be willing to use an approved method of contraception from screening until 4 months after the third immunisation. Sexually active men in heterosexual relationships must be willing to use an approved method of contraception with their partners from screening until 4 months after the third immunisation.
- Confirmed HIV-2 seropositive
- Positive pregnancy test
- Participation in another clinical trial within 12 weeks of study entry
- History of autoimmune disease other than HIV-related auto-immune disease which has resolved with ART
- History or clinical manifestations of any physical or psychiatric disorder which could impair the subject's ability to complete the study
- History of anaphylaxis or severe adverse reaction to vaccines
- History of alcohol or drug dependency which could, in the opinion of the investigators, impair the subject's ability to complete the study
- Previous immunisation with a recombinant MVA vaccine
- Immunisation with any experimental immunogens within 6 months of study entry
- Receipt of blood products or immunoglobulins within 6 months of study entry
- Treatment for cancer or lymphoproliferative disease within 1 year of study entry
- Receipt of vaccines other than Hepatitis B vaccine within 2 weeks of study entry or planned receipt within 2 weeks of vaccination
- Any other prior therapy which, in the opinion of the investigators, would make the individual unsuitable for the study or influence the results of the study
- Current or recent use (within last 3 months) of interferon or systemic corticosteroids or other immunosuppressive agents
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method The proportion of volunteers who develop a grade 3 or 4 local or systemic reactions Actively collected data throughout the study until 6 months after the last vaccination
- Secondary Outcome Measures
Name Time Method PBMC will be stored for other exploratory assays to characterise vaccine-expanded T cell populations such as IL-10 secretion and CFSE proliferation assays. Screen (≤ day -28); Day 0; Day 14; Day 28; Day 42; Day 56; Day 84; Day 112; Day 182; Final visit (day 266 / early termination) Evaluation of the effect of MVA.HIVconsv vaccinations on viral suppressive capacity of CD8+ T cells in vitro, using a novel flow cytometric assay Screen (≤ day -28); Day 0; Day 14; Day 28; Day 42; Day 56; Day 84; Day 112; Day 182; Final visit (day 266 / early termination) Magnitude and phenotype, including but not limited to activation status, of HIV-1-specific CD8+ T cell populations identified by tetramer staining before and after vaccination, in selected volunteers with appropriate HLA class I alleles. Screen (≤ day -28); Day 0; Day 14; Day 28; Day 42; Day 56; Day 84; Day 112; Day 182; Final visit (day 266 / early termination) A descriptive summary of grade 3 or 4 local and systemic events, including laboratory abnormalities Actively collected data throughout the study until 6 months after the last vaccination A descriptive summary of serious adverse events, including laboratory abnormalities Actively collected data throughout the study until 6 months after the last vaccination The proportion of volunteers who develop CD8+ T cell responses to a new HIV-1 epitope, as determined by IFN-γ ELISPOT assay Screen (≤ day -28); Day 0; Day 14; Day 28; Day 42; Day 56; Day 84; Day 112; Day 182; Final visit (day 266 / early termination) The proportion of volunteers in whom the magnitude of CD8+ T cell responses to HIVconsv peptides increases by ≥ 3-fold, as determined by IFN-γ ELISPOT assay Screen (≤ day -28); Day 0; Day 14; Day 28; Day 42; Day 56; Day 84; Day 112; Day 182; Final visit (day 266 / early termination) Serum and plasma will be stored for investigation of binding and neutralising antibodies to vaccinia and of pro-inflammatory cytokines. Screen (≤ day -28); Day 0; Day 14; Day 28; Day 42; Day 56; Day 84; Day 112; Day 182; Final visit (day 266 / early termination)
Trial Locations
- Locations (2)
Weatherall Institute of Molecular Medicine
🇬🇧Oxford, Oxons, United Kingdom
Oxford Genitourinary Medicine
🇬🇧Oxford, Oxon, United Kingdom
Weatherall Institute of Molecular Medicine🇬🇧Oxford, Oxons, United Kingdom