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

• ClinicalTrials.gov Identifier: NCT01024842
• Recruitment Status: Terminated
• First Posted: December 3, 2009
• Last Update Posted: June 8, 2016
• Sponsor: University of Oxford
• Collaborator: Medical Research Council
• Information provided by (Responsible Party): University of Oxford

Tracking Information

• First Submitted Date: December 1, 2009
• First Posted Date: December 3, 2009
• Last Update Posted Date: June 8, 2016
• Study Start Date: December 2009
• Actual Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Immunogenicity of MVA.HIVconsv in HIV-1 Seropositive Adults on HAART
• Official Title: 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: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: HIV-1

Intervention

• 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

• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: June 7, 2016): 19
• Original Estimated Enrollment (submitted: December 1, 2009): 20
• Actual Study Completion Date: November 2013
• Actual Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT01024842
• Other Study ID Numbers: HIV-CORE 001
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• 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: University of Oxford
• Collaborators: Medical Research Council

Investigators

• 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