Safety and Immunogenicity of MVA.HIVconsv in HIV-1 Seropositive Adults on HAART
7 juni 2016 bijgewerkt door: University of Oxford
HIV-CORE 001 - A Randomised Placebo-controlled Study to Evaluate the Safety and Immunogenicity of a Candidate HIV-1 Vaccine, MVA.HIVconsv, Delivered by Intramuscular Needle Injection to HIV-1 Seropositive Adult Subjects Receiving Antiretroviral Therapy (ART).
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.
Studie Overzicht
Toestand
Beëindigd
Conditie
Interventie / Behandeling
Studietype
Ingrijpend
Inschrijving (Werkelijk)
19
Fase
- Fase 1
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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Oxon
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Oxford, Oxon, Verenigd Koninkrijk, OX3 7LJ
- Oxford Genitourinary Medicine
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Oxons
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Oxford, Oxons, Verenigd Koninkrijk, OX3 9DS
- Weatherall Institute of Molecular Medicine
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Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar tot 60 jaar (Volwassen)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
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
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Verviervoudigen
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: Low dose vaccinees
Individuals will receive three intramuscular injections of MVA.HIVconsv alone at a dose of 1x10^8 pfu.
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Three intramuscular injections of MVA.HIVconsv alone at a dose of 1x10^8 pfu at week 0, 4 and 12.
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Experimenteel: High dose vaccinees
Individuals will receive three intramuscular injections of MVA.HIVconsv alone at a dose of 4x10^8 pfu.
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Three intramuscular injections of MVA.HIVconsv alone at a dose of 4x10^8 pfu at week 0, 4 and 12.
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Placebo-vergelijker: Low dose placebo
Individuals will receive three intramuscular injections of low dose placebo
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Three intramuscular injections of placebo alone (200ul) at week 0, 4 and 12.
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Placebo-vergelijker: High dose placebo
Individuals will receive three intramuscular injections of high dose placebo
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Three intramuscular injections of placebo alone (800ul) at week 0, 4 and 12.
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
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The proportion of volunteers who develop a grade 3 or 4 local or systemic reactions
Tijdsspanne: Actively collected data throughout the study until 6 months after the last vaccination
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Actively collected data throughout the study until 6 months after the last vaccination
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Secundaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
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A descriptive summary of grade 3 or 4 local and systemic events, including laboratory abnormalities
Tijdsspanne: Actively collected data throughout the study until 6 months after the last vaccination
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Actively collected data throughout the study until 6 months after the last vaccination
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A descriptive summary of serious adverse events, including laboratory abnormalities
Tijdsspanne: Actively collected data throughout the study until 6 months after the last vaccination
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Actively collected data throughout the study until 6 months after the last vaccination
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The proportion of volunteers who develop CD8+ T cell responses to a new HIV-1 epitope, as determined by IFN-γ ELISPOT assay
Tijdsspanne: 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)
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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)
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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
Tijdsspanne: 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)
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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)
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Evaluation of the effect of MVA.HIVconsv vaccinations on viral suppressive capacity of CD8+ T cells in vitro, using a novel flow cytometric assay
Tijdsspanne: 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)
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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)
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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.
Tijdsspanne: 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)
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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)
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PBMC will be stored for other exploratory assays to characterise vaccine-expanded T cell populations such as IL-10 secretion and CFSE proliferation assays.
Tijdsspanne: 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)
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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)
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Serum and plasma will be stored for investigation of binding and neutralising antibodies to vaccinia and of pro-inflammatory cytokines.
Tijdsspanne: 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)
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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)
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Medewerkers
Onderzoekers
- Hoofdonderzoeker: Andrew McMichael, University of Oxford
Publicaties en nuttige links
De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start
1 december 2009
Primaire voltooiing (Werkelijk)
1 november 2013
Studie voltooiing (Werkelijk)
1 november 2013
Studieregistratiedata
Eerst ingediend
1 december 2009
Eerst ingediend dat voldeed aan de QC-criteria
1 december 2009
Eerst geplaatst (Schatting)
3 december 2009
Updates van studierecords
Laatste update geplaatst (Schatting)
8 juni 2016
Laatste update ingediend die voldeed aan QC-criteria
7 juni 2016
Laatst geverifieerd
1 juni 2016
Meer informatie
Termen gerelateerd aan deze studie
Andere studie-ID-nummers
- HIV-CORE 001
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
JA
Beschrijving IPD-plan
Data are presented in a manuscript submitted to a peer-reviewed journal.
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