Safety and Immunogenicity of MVA.HIVconsv in HIV-1 Seropositive Adults on HAART
7 juin 2016 mis à jour par: 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.
Aperçu de l'étude
Statut
Résilié
Les conditions
Intervention / Traitement
Type d'étude
Interventionnel
Inscription (Réel)
19
Phase
- La phase 1
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Oxon
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Oxford, Oxon, Royaume-Uni, OX3 7LJ
- Oxford Genitourinary Medicine
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Oxons
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Oxford, Oxons, Royaume-Uni, OX3 9DS
- Weatherall Institute of Molecular Medicine
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans à 60 ans (Adulte)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
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
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Quadruple
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: 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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Expérimental: 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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Comparateur placebo: 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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Comparateur placebo: 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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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
|---|---|
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The proportion of volunteers who develop a grade 3 or 4 local or systemic reactions
Délai: 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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Mesures de résultats secondaires
Mesure des résultats |
Délai |
|---|---|
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A descriptive summary of grade 3 or 4 local and systemic events, including laboratory abnormalities
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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.
Délai: 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.
Délai: 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.
Délai: 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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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Andrew McMichael, University of Oxford
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 décembre 2009
Achèvement primaire (Réel)
1 novembre 2013
Achèvement de l'étude (Réel)
1 novembre 2013
Dates d'inscription aux études
Première soumission
1 décembre 2009
Première soumission répondant aux critères de contrôle qualité
1 décembre 2009
Première publication (Estimation)
3 décembre 2009
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
8 juin 2016
Dernière mise à jour soumise répondant aux critères de contrôle qualité
7 juin 2016
Dernière vérification
1 juin 2016
Plus d'information
Termes liés à cette étude
Autres numéros d'identification d'étude
- HIV-CORE 001
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
OUI
Description du régime IPD
Data are presented in a manuscript submitted to a peer-reviewed journal.
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .