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Safety and Immunogenicity of MVA.HIVconsv in HIV-1 Seropositive Adults on HAART

7. juni 2016 oppdatert av: 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.

Studieoversikt

Status

Avsluttet

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Faktiske)

19

Fase

  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Storbritannia
    • Oxon
      • Oxford, Oxon, Storbritannia, OX3 7LJ
        • Oxford Genitourinary Medicine
    • Oxons
      • Oxford, Oxons, Storbritannia, OX3 9DS
        • Weatherall Institute of Molecular Medicine

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 60 år (Voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Firemannsrom

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Low dose vaccinees
Individuals will receive three intramuscular injections of MVA.HIVconsv alone at a dose of 1x10^8 pfu.
Biologisk: MVA.HIVconsv low dose
Three intramuscular injections of MVA.HIVconsv alone at a dose of 1x10^8 pfu at week 0, 4 and 12.
Eksperimentell: High dose vaccinees
Individuals will receive three intramuscular injections of MVA.HIVconsv alone at a dose of 4x10^8 pfu.
Biologisk: MVA.HIVconsv high dose
Three intramuscular injections of MVA.HIVconsv alone at a dose of 4x10^8 pfu at week 0, 4 and 12.
Placebo komparator: Low dose placebo
Individuals will receive three intramuscular injections of low dose placebo
Annen: Placebo low dose
Three intramuscular injections of placebo alone (200ul) at week 0, 4 and 12.
Placebo komparator: High dose placebo
Individuals will receive three intramuscular injections of high dose placebo
Annen: Placebo high dose
Three intramuscular injections of placebo alone (800ul) at week 0, 4 and 12.

Hva måler studien?

Primære resultatmål

Resultatmål
Tidsramme
The proportion of volunteers who develop a grade 3 or 4 local or systemic reactions
Tidsramme: Actively collected data throughout the study until 6 months after the last vaccination
Actively collected data throughout the study until 6 months after the last vaccination

Sekundære resultatmål

Resultatmål
Tidsramme
A descriptive summary of grade 3 or 4 local and systemic events, including laboratory abnormalities
Tidsramme: Actively collected data throughout the study until 6 months after the last vaccination
Actively collected data throughout the study until 6 months after the last vaccination
A descriptive summary of serious adverse events, including laboratory abnormalities
Tidsramme: Actively collected data throughout the study until 6 months after the last vaccination
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
Tidsramme: 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)
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
Tidsramme: 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)
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
Tidsramme: 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)
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.
Tidsramme: 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)
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.
Tidsramme: 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)
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.
Tidsramme: 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)
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)

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

University of Oxford

Samarbeidspartnere

Medical Research Council

Etterforskere

  • Hovedetterforsker: Andrew McMichael, University of Oxford

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. desember 2009

Primær fullføring (Faktiske)

1. november 2013

Studiet fullført (Faktiske)

1. november 2013

Datoer for studieregistrering

Først innsendt

1. desember 2009

Først innsendt som oppfylte QC-kriteriene

1. desember 2009

Først lagt ut (Anslag)

3. desember 2009

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

8. juni 2016

Siste oppdatering sendt inn som oppfylte QC-kriteriene

7. juni 2016

Sist bekreftet

1. juni 2016

Mer informasjon

Begreper knyttet til denne studien

Andre studie-ID-numre

  • HIV-CORE 001

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

JA

IPD-planbeskrivelse

Data are presented in a manuscript submitted to a peer-reviewed journal.

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