HIV-1
Conditions
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.
Interventions
BIOLOGICALMVA.HIVconsv low dose
Three intramuscular injections of MVA.HIVconsv alone at a dose of 1x10\^8 pfu at week 0, 4 and 12.
OTHERPlacebo low dose
Three intramuscular injections of placebo alone (200ul) at week 0, 4 and 12.
BIOLOGICALMVA.HIVconsv high dose
Three intramuscular injections of MVA.HIVconsv alone at a dose of 4x10\^8 pfu at week 0, 4 and 12.
OTHERPlacebo high dose
Three intramuscular injections of placebo alone (800ul) at week 0, 4 and 12.
Sponsors
Medical Research Council
University of Oxford
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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) |
| 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 |
| 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) |
| 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) |
| 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) |
| 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) |
Countries
United Kingdom
Outcome results
None listed