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

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.

Study Overview

• Status: Terminated
• Conditions: HIV-1
• Intervention / Treatment: Biological: MVA.HIVconsv low dose; Biological: MVA.HIVconsv high dose; Other: Placebo low dose; Other: Placebo high dose

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dose vaccinees; Individuals will receive three intramuscular injections of MVA.HIVconsv alone at a dose of 1x10^8 pfu.	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.
Experimental: High dose vaccinees; Individuals will receive three intramuscular injections of MVA.HIVconsv alone at a dose of 4x10^8 pfu.	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.
Placebo Comparator: Low dose placebo; Individuals will receive three intramuscular injections of low dose placebo	Other: Placebo low dose; Three intramuscular injections of placebo alone (200ul) at week 0, 4 and 12.
Placebo Comparator: High dose placebo; Individuals will receive three intramuscular injections of high dose placebo	Other: Placebo high dose; Three intramuscular injections of placebo alone (800ul) at week 0, 4 and 12.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The proportion of volunteers who develop a grade 3 or 4 local or systemic reactions	Actively collected data throughout the study until 6 months after the last vaccination

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: Medical Research Council
• Investigators: Principal Investigator: Andrew McMichael, University of Oxford

Publications and helpful links

General Publications

• Hancock G, Moron-Lopez 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: December 1, 2009
• First Submitted That Met QC Criteria: December 1, 2009
• First Posted (Estimate): December 3, 2009

Study Record Updates

• Last Update Posted (Estimate): June 8, 2016
• Last Update Submitted That Met QC Criteria: June 7, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: HIV-CORE 001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data are presented in a manuscript submitted to a peer-reviewed journal.