Press Release

PRESS RELEASE N° 001

By

Istituto Superiore di Sanità (Italy)
and
National Department of Health (South Africa)
under
the ‘Program to support the Ministry of Health of South Africa in the implementation of a national program of global response to HIV & AIDS’
funded by the Italian Cooperation

HIV/AIDS: STARTING OF the Phase II VACCINE TRIAL
BASED ON THE TAT PROTEIN

The clinical trial: “A Phase Il, Randomized, Double-Blind, Placebo-Controlled Trial to evaluate the Immunogenicity and Safety of a Therapeutic, Recombinant, Biologically Active HIV-1 Tat Protein Vaccine in HIV-Infected, Anti-Tat Negative, ARV-Treated Adult Volunteers” (ISS T-003) is imminently starting at the Medunsa Clinical Research Unit (MeCRU), Ga-Rankuwa. The trial is going to test the candidate vaccine against HIV/AIDS based on the biologically active HIV-1 Tat protein, conceived and developed by the National AIDS Centre (CNAIDS) of the Italian Istituto Superiore di Sanità (ISS).

The clinical trial ISS T-003 is part of a cooperation/joint program between the Governments of Italy and South Africa aimed at the implementation of a national program of global response to HIV & AIDS (‘Program to support the Ministry of Health of South Africa in the implementation of a national program of global response to HIV & AIDS’).

The Program, funded by the Italian Ministry of Foreign Affairs, Directorate General of Development Cooperation (MAE-DGCS), is implemented by the ISS/CNAIDS in collaboration with the South African National Department of Health (NDOH) and the South African AIDS Vaccine Initiative of the Medical Research Council (MRC-SAAVI).

The Program is structured in the following three components:

1. Strengthening of healthcare services and reinforcement of the governance capacity of the healthcare system in the program intervention areas (Services Component);
2. Establishing a local Good Manufacturing Practice (GMP)-certified facility for recombinant protein vaccine products (Production Component);
3. Conducting a phase II clinical trial in South Africa testing the Tat HIV vaccine candidate (Vaccine Component).

The implementation of the components of the program, including preparedness for the clinical trial, started at the end of 2009.

The Services Component focuses on HIV/AIDS care, and in particular on ARV treatment programs in the view of maximizing the synergy between the clinical research and the health services. The intervention is directed toward forty earmarked health clinics in Gauteng, Eastern Cape and Mpumalanga, identified jointly with the Provincial DOHs. Intervention is directed at i) upgrading the infrastructure, providing equipment, and contributing to staff capacity building to enhance service delivery and; ii) strengthening the District Health Information System.

The Production Component is setting the basis for the development of a local production facility for vaccine manufacturing under GMP standards at The Biovac Institute (TBI) in Cape Town. The achievement of this objective relies on the following sub-projects: 1) Technology Transfer toward the production process, recruitment and training plans, skills development; 2) Facility Project, tasked with the equipment of a GMP Production Facility; 3) Operationalization Project for ensuring preparedness to the GMP vaccine manufacturing process.

The Vaccine Component foresees the preparation and conduct of the ISS-T003 clinical trial.

An independent International Scientific Advisory Committee (ISAC), with advisory functions to the project Steering Committee, will periodically assess the progress of the three components of the Program.

The clinical trial ISS T-003 will be conducted at the Medunsa Clinical Research Unit (MeCRU), located at the University of Limpopo - Medunsa Campus, Ga-Rankuwa, Gauteng Province. The involvement of an additional trial site, the Walter Sisulu University, HIV Vaccine Research Unit (WSUHVRU) (Mthatha, Eastern Cape), is envisaged by the last quarter of 2011, once the Research Unit is fully capacitated.

The ISS T-003 protocol has been approved by the Medicines Control Council (MCC) and by the Medunsa Research and Ethics Committee (MREC).

The study will involve the recruitment of 200 participants between 18 and 45 years of age. The objective is the evaluation of the immunogenicity of the vaccine candidate - at a dosage of 30 µg when given intradermally on 3 occasions at 4-weekly intervals - as well as confirmation of the safety of the candidate vaccine as previously tested in Italy.

Subjects eligible for the study will be individuals with chronic HIV infection on ARV treatment. The enrolment of the volunteers will be performed at MeCRU.

The Tat vaccine has shown to be safe and capable of inducing specific antibody and cellular immune responses in preclinical studies in monkeys and in previous phase I clinical trials conducted in Italy. Furthermore, the results of an ad hoc interim analysis on 87 volunteers of the phase II trial ISS T-002, under completion in Italy in 11 Clinical Centres, indicate that the Tat vaccine represents a promising tool to improve immune functions in HIV-infected patients treated with antiretroviral drugs [Ensoli et al, PLoS One,2010, 5 (11): e13540]. The Tat vaccine showed a novel and key role in reducing the immune system alterations observed in HIV infection and usually persistent even under successful ARV treatment. In addition, those patients who are the most immunocompromised appeared to benefit the most from Tat vaccination.

The clinical trial is supported by the following independent committees, each with a specific function:

• A Data Safety Monitoring Board (“DSMB”) – composed of international experts with well-documented experience in the field of HIV/AIDS. The DSMB will monitor the safety of the vaccine by periodically evaluating all related data during the trial.

• An International Advisory Board (“IAB”) - composed of international experts in the immunological, virological or vaccine field. The IAB will provide independent advice to the trial Sponsor (ISS) in taking decisions, alternative strategies and solutions in any critical situations that may ensue from the study.

• A Community Advisory Group (CAG) and Community Advisory Board (CAB), comprising representatives of the communities from the Clinical Research Unit (CRU) area. These Community bodies will play a key role in the involvement of the community, through the organisation of educational activities and awareness events. Furthermore, they will give advice to the Principal Investigator and to the Sponsor in ensuring the well being of the trial participants.

Further details on the HIV-1 Tat protein vaccine are available on the ISS website at: www.iss.it/aids, and www.hiv1tat-vaccines.info/index.php

SPOKESPEOPLE

For the ISS T-003 clinical trial

Dr Barbara Ensoli
ISS, National AIDS Center
Director
(Role in Program: Project Director, Italy)

Ms Elise Levendal
SAAVI
Interim Director
(Role in Program: Leader of Component 3)

Prof. Maphoshane Nchabeleng
University of Limpopo – Medunsa Campus
Head of Department: Microbiology
Trial Site Director: Medunsa Clinical Research Unit (MeCRU)
(Role in the Program: Principal Investigator for MeCRU)

For the Program

H.E. Elio Menzione
Ambassador of Italy to South Africa

Barbara Ensoli
ISS, National AIDS Center
Director
(Role in Program: Project Director, Italy)

Paolo Monini
ISS, National AIDS Center
Division of Virus-Host Interaction
Director
(Role in Program: Head of Project, South Africa)

Yogan Pillay
National Department of Health (NDOH)
Deputy Director General: Strategic Health Programmes
(Role in Program: Project Director, South Africa)

Morena Makhoana
The BIOVAC Institute (TBI)
Chief Executive Officer
(Role in the Program: Leader, Component 2)

Elise Levendal
SAAVI
Interim Director
(Role in Program: Leader of Component 3)

Prof. Maphoshane Nchabeleng
University of Limpopo – Medunsa Campus
Head of Department: Microbiology
Trial Site Director: Medunsa Clinical Research Unit (MeCRU)
(Role in the Program: Principal Investigator for ISS T-003 at MeCRU)

Prof. Jimmy Chandia
Walter Sisulu University
Acting Head: Department of Family Medicine, Faculty of Health Sciences
Trial Site Director: Walter Sisulu University, HIV Vaccine Research Unit (WSUHVRU)
(Role in the Program: Principal Investigator for ISS OBS T-004 study at WSUHVRU)

To reach the spokespeople, please contact the following Media Liaison persons

DGCS
DGCS (Direzione Generale per la Cooperazione allo Sviluppo) is one of the Directorates of the Italian Ministry of Foreign Affairs and is responsible for the Italian ODA (Official Development Assistance). In South Africa, DGCS currently finances several initiatives, some directly managed, and some others implemented by partner institutions like ISS and Non-governmental Organisations (NGOs). Health in South Africa is the main sector of support with HIV-AIDS and TB as the present priority areas. Within the HIV project implemented by ISS, the DGCS, in conjunction with the NDOH, will ensure the monitoring and evaluation of the whole Program. Furthermore, DGCS will finance the United Nations (UN) agency charged with the coordination of the International Scientific Advisory Committee (ISAC).

ISS
The ISS is the leading technical and scientific public body of the Italian National Health Service, with tasks of research, control, training and consultation in the interest of the protection of public health in Italy. CNAIDS of the ISS coordinates studies on HIV and other AIDS-related viral infections and cancers and has conducted research for over 13 years on HIV/AIDS vaccines, focusing its efforts on the HIV-1 Tat vaccine candidate, based on the HIV-1 Tat protein. The Center has sponsored and conducted phase I and phase II clinical trials testing the Tat vaccine in Italy.

NDOH
The National Department of Health (NDOH) is the custodian of health care in the Republic of South Africa. The provision of strategic leadership and stewardship, guided by the core values enshrined in the Constitution and the National Health Act, ensure that high quality health care is provided to all citizens of the Republic of South Africa. The Department provides high quality services through an over arching framework, which consists of the following:

• Providing strategic leadership and the creation of a social compact for better health outcomes
• Implementing National Health Insurance
• Improving the quality of health services
• Overhauling the health care system and improving its management
• Improving human resource planning, development and management
• Revitalizing infrastructure
• Accelerating the implementation of HIV AND AIDS and Sexually Transmitted Infections National Strategic Plan 2007- 2011, and increasing the focus on TB and other communicable diseases
• Implementing mass mobilization for better health among the population
• Reviewing the Drug Policy
• Strengthening research and development

The Negotiated Service Delivery Agreement (NSDA) is intended to further strengthen activities toward the following four outputs:

• Increasing life expectancy
• Decreasing Maternal and Child mortality
• Combating HIV and AIDS and decreasing the burden of diseases from Tuberculosis
• Strengthening Health System Effectiveness

The involvement of the Department in the ‘Program to support the Ministry of Health of South Africa in the implementation of a national program of global response to HIV & AIDS’ is to further strengthen health outcomes, improve quality of life and ensure a responsive and well functioning health care system.

MRC-SAAVI
The South African Medical Research Council (MRC) is a statutory organisation established by an Act of Parliament in 1969. Its mission is to improve the nation’s health and quality of life through promoting and conducting relevant and responsive health research.

The South African AIDS Vaccine Initiative (SAAVI) was established by the South African government in 1999 to co-ordinate the research and development of an affordable, effective and locally relevant HIV vaccine for southern Africa. SAAVI is a lead programme of the South African MRC. The MRC-SAAVI has been indicated by the NDOH as the local operational partner of ISS, in the implementation of the ISS T-003-related activities.

MeCRU, University of Limpopo – Medunsa Campus
The Medunsa Clinical Research Unit (MeCRU) was established at the University of Limpopo - Medunsa Campus, Department of Medical Microbiology in July 2005, as a collaboration with the Department of Virology and the Medunsa Institute of Community Outreach Services (Medicos). The Unit conducts a variety of clinical trials on HIV/AIDS vaccines, the Human Papillomavirus (HPV) and opportunistic infections. It is strategically located at the University of Limpopo - Medunsa Campus where there is wide spectrum of qualified researchers from various fields of the health fraternity and is adjacent to Dr George Mukhari Hospital (DGM), a 1400-bed tertiary hospital.

The Unit has a contract Research laboratory to support the clinical trials which is 500m away from the trial site in the Research Section of the Department of Microbiological Pathology. The laboratory is accredited by SANAS from 2004 to date (Molecular Biology section, Serology, Bacteriology). It provides a variety of support to the clinical trials, including Peripheral Blood Mononuclear Cells (PBMC) isolation and a bulk specimen storage system. It is in close proximity to the SANAS-Accredited NHLS-Microbiology, Virology, Chemistry, Haematology, Anatomical Pathology (Histology, Cytology) facility.

MeCRU was established with the support of the South African Medical Research Council (MRC) through its lead programme, the South African AIDS Vaccine Initiative (SAAVI). MeCRU is one of the sites which will conduct the ISS T-003 Tat HIV vaccine clinical trial.

HIV Vaccine Research Unit, Walter Sisulu University
Walter Sisulu University (WSU) is a developmental, comprehensive university focusing on urban renewal and rural development. It may be characterized as scientific, technological, innovative and responsive to local community needs, the requirements of commerce and industry and the socio-economic niche areas of national government. Operating across four campuses in the Eastern Cape: Mthatha, Butterworth, Buffalo City (East London) and Queenstown, WSU has a student population of over 24,000 and offers diplomas, degrees and post-graduate studies in four faculties: Health Sciences; Education; Science, Engineering and Technology and Business, Management Sciences and Law.

The Faculty of Health Sciences recently celebrated 25 years of Socially Accountable medical education and is a leader in Problem- Based Learning (PBL), Community-Based Education (CBE) and Community Partnerships in Africa. One of its core principles is developing an appropriate curriculum that is based on the primary health care approach and guided by health and social needs. The Faculty is headquartered at the Mthatha Campus but has an Academic Health Service Complex that spreads throughout the Eastern Cape including Mthatha Hospital Complex, East London Hospital Complex, Port Elizabeth Hospital Complex, about 15 District Hospitals mainly in the North Eastern Region of the Eastern Cape, and seven Community Health Centres.

The HIV Vaccine Research Unit (HVRU) falls under the WSU Faculty of Health Sciences. Development of the site began in 2006 with funding from the South African AIDS Vaccine Initiative (SAAVI), a lead programme of the South African Medical Research Council (MRC) via SAAVI’s grant from the National Department of Health (NDOH). Since 2009, the site has been funded via the ‘Program to support the Ministry of Health of South Africa in the implementation of a national program of global response to HIV & AIDS’. This Program is funded by the Italian Ministry of Foreign Affairs, Directorate General of Development Cooperation (MAE-DGCS), and is implemented by the National AIDS Centre (CNAIDS) of the National Institute of Health of Italy (Istituto Superiore di Sanità or ISS), in cooperation with the South African National Department of Health (NDOH) supported by the MRC-SAAVI. Since November 2009 the HVRU has embarked on employment and training of several trial site staff as well as the purchase of relevant furniture and equipment. Renovations of an existing building in the old Mthatha Hospital grounds should be complete by mid 2011. The site is expected to be ready to conduct the T-003 Tat HIV vaccine trial towards the end of 2011.