ITV Extension Study

Condition(s) targeted: HIV

Intervention: recombinant fowlpoxvirus (rFPV) expressing HIV gag-pol antigens (Biological); HIV gag-pol antigens and interferon-gamma (IFN-y) (Biological)

Phase: Phase 1/Phase 2

Status: Completed

Sponsored by: The National Centre in HIV Epidemiology and Clinical Research

Official(s) and/or principal investigator(s):
David A Cooper, AO DSc MD FRACP FRCPA FRCP, Principal Investigator, Affiliation: National Centre in HIV Epidemiology and Clinical Research

The objective of this phase I/II therapeutic human immunodeficiency virus (HIV) vaccine candidate study is to provide proof of concept for a HIV antigen delivery system in terms of safety, virological effects and selected immune responses in HIV infected individuals after cessation of antiretroviral combination therapy (ART).

Official title: An Extension Study to Protocol VIR-NCHR-01 to Assess the Antiretrovirological Properties of a Therapeutic HIV Vaccine Candidate Based on Recombinant Fowlpox Virus (rFPV) (ITV Extension Study)

Study design: Interventional, Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Time weighted area under the curve change from plasma HIV-RNA VL at baseline (day 0) until reintroduction of antiretroviral therapy

Secondary outcome:

Log plasma HIV-RNA load after cessation of combination ART (post-vaccination viral load (VL) set-point)

Kinetics and rate of VL recrudescence and median time to re-initiation of ART

CD8+ T-cell responses to HIV antigens assessed through:

Enzyme linked immunospot (ELISPOT) assay of IFN-y secreting cells

Intracellular Cytokine Cytometry (ICC) for IFN-y and CD69

Human Leucocyte Antigen (HLA) class I/ I matched tetramer analyses for HIV epitope specific CD8+/CD4+ T –cells

CD4+/CD8+ T-cell count changes

Detailed description: A multi-centre, double-blind, placebo-controlled, 20-week parallel group extension study to the VIR-NCHR-01 protocol (ITV study). The purpose of the extension study is to assess the safety and virological effects of a therapeutic HIV vaccine strategy in HIV-1 infected adults currently enrolled in the ITV study after cessation of antiretroviral therapy. Two active candidate vaccines will be studied in this trial: The active treatment arms will receive recombinant fowlpoxvirus (rFPV) expressing HIV gag-pol antigens or HIV gag-pol antigens and interferon-gamma (IFN-y) in diluent. Vaccines will be delivered by intramuscular injection.

Minimum age: 18 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- HIV-1 infected individuals eligible and still fulfilling the criteria for the VIR-NCHR-01 protocol (ITV study)

- Received all 3 immunisations

- Remained in follow-up for at least 52 weeks

- Continued to take combination antiretroviral therapy with no evidence of treatment failure at the time entering the roll-over phase

- Written informed consent obtained

Criteria for Withdrawal of Study Participants

- Incidental or progression of disease which, in the opinion of the principal investigator, should preclude further study participation

- If the study participant required cytotoxic or immunosuppressive chemo- or radiation therapy

- If the study participant required any medications that when combined with the study vaccination, would in the opinion of the principal investigator, jeopardise the validity of the individual’s continued participation

- Administration of prohibited alternative therapy

- Study participant non-compliance

- All study participants are required to adhere to the protocol evaluation schedule. Failure to adhere with this schedule without having first provided justification may result in the participant being withdrawn from the study

- At the request of the study participant or principal investigator without prejudice to future health care

- In the opinion of the investigator, if it is not in the patient’s best interests to continue the study

- At the request of the National Centre in HIV Epidemiology and Clinical Research (NCHECR) with reasonable cause

- At the advice of the Data Safety Monitoring Board (DSMB)

407 Doctors, Sydney, New South Wales 2010, Australia

Ground Zero Medical Practice, Sydney, New South Wales 2010, Australia

Holdsworth House Medical Practice, Sydney, New South Wales 2010, Australia

St Vincents Hospital, Sydney, New South Wales 2010, Australia

Carlton Clinic, Melbourne, Victoria 3053, Australia

The Alfred Hospital, Melbourne, Victoria 3004, Australia

(National Centre in HIV Epidemiology and Clinical Research Homepage)

Starting date: September 2002
Ending date: September 2003
Last updated: February 26, 2007