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

Purpose

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.

Condition	Intervention	Phase
HIV-1	Biological: MVA.HIVconsv low dose Other: Placebo low dose Biological: MVA.HIVconsv high dose Other: Placebo high dose	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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).

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

Further study details as provided by University of Oxford:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	December 2009
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01024842

Contacts

Contact: Lucy Dorrell

01865 222145

lucy.dorrell@imm.ox.ac.uk

Locations

United Kingdom
Weatherall Institute of Molecular Medicine	Not yet recruiting
Oxford, Oxons, United Kingdom, OX3 9DS
Oxford Genitourinary Medicine	Recruiting
Oxford, Oxon, United Kingdom, OX3 7LJ
Principal Investigator: Lucy Dorrell

Sponsors and Collaborators

University of Oxford

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

More Information

No publications provided

Responsible Party:	University of Oxford
ClinicalTrials.gov Identifier:	NCT01024842 History of Changes
Other Study ID Numbers:	HIV-CORE 001
Study First Received:	December 1, 2009
Last Updated:	August 1, 2012
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

ClinicalTrials.gov processed this record on May 23, 2013