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

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ClinicalTrials.gov Identifier: NCT01024842
Recruitment Status : Terminated (Slow recruitment therefore study was stopped after 95% volunteers were enrolled.)
First Posted : December 3, 2009
Last Update Posted : June 8, 2016
Sponsor:
Collaborator:
Medical Research Council
Information provided by (Responsible Party):
University of Oxford

Tracking Information
First Submitted Date  ICMJE December 1, 2009
First Posted Date  ICMJE December 3, 2009
Last Update Posted Date June 8, 2016
Study Start Date  ICMJE December 2009
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 1, 2009)
The proportion of volunteers who develop a grade 3 or 4 local or systemic reactions [ Time Frame: Actively collected data throughout the study until 6 months after the last vaccination ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 1, 2009)
  • A descriptive summary of grade 3 or 4 local and systemic events, including laboratory abnormalities [ Time Frame: Actively collected data throughout the study until 6 months after the last vaccination ]
  • A descriptive summary of serious adverse events, including laboratory abnormalities [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Immunogenicity of MVA.HIVconsv in HIV-1 Seropositive Adults on HAART
Official Title  ICMJE 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).
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE HIV-1
Intervention  ICMJE
  • Biological: MVA.HIVconsv low dose
    Three intramuscular injections of MVA.HIVconsv alone at a dose of 1x10^8 pfu at week 0, 4 and 12.
  • Other: Placebo low dose
    Three intramuscular injections of placebo alone (200ul) at week 0, 4 and 12.
  • Biological: MVA.HIVconsv high dose
    Three intramuscular injections of MVA.HIVconsv alone at a dose of 4x10^8 pfu at week 0, 4 and 12.
  • Other: Placebo high dose
    Three intramuscular injections of placebo alone (800ul) at week 0, 4 and 12.
Study Arms  ICMJE
  • Experimental: Low dose vaccinees
    Individuals will receive three intramuscular injections of MVA.HIVconsv alone at a dose of 1x10^8 pfu.
    Intervention: Biological: MVA.HIVconsv low dose
  • Experimental: High dose vaccinees
    Individuals will receive three intramuscular injections of MVA.HIVconsv alone at a dose of 4x10^8 pfu.
    Intervention: Biological: MVA.HIVconsv high dose
  • Placebo Comparator: Low dose placebo
    Individuals will receive three intramuscular injections of low dose placebo
    Intervention: Other: Placebo low dose
  • Placebo Comparator: High dose placebo
    Individuals will receive three intramuscular injections of high dose placebo
    Intervention: Other: Placebo high dose
Publications * Hancock G, Morón-López S, Kopycinski J, Puertas MC, Giannoulatou E, Rose A, Salgado M, Hayton EJ, Crook A, Morgan C, Angus B, Chen F, Yang H, Martinez-Picado J, Hanke T, Dorrell L. Evaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjects. J Int AIDS Soc. 2017 May 19;20(1):21171. doi: 10.7448/IAS.20.1.21171.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 7, 2016)
19
Original Estimated Enrollment  ICMJE
 (submitted: December 1, 2009)
20
Actual Study Completion Date  ICMJE November 2013
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01024842
Other Study ID Numbers  ICMJE HIV-CORE 001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Data are presented in a manuscript submitted to a peer-reviewed journal.
Responsible Party University of Oxford
Study Sponsor  ICMJE University of Oxford
Collaborators  ICMJE Medical Research Council
Investigators  ICMJE
Principal Investigator: Tomas Hanke University of Oxford
Principal Investigator: Andrew McMichael University of Oxford
Principal Investigator: Lucy Dorrell University of Oxford
PRS Account University of Oxford
Verification Date June 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP