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Phase 2 Proof-of-Concept Study Initiated for Investigational HIV/AIDS Vaccine
The study – a collaboration of Merck, the HVTN, and the National Institute of Allergy and Infectious Diseases (NIAID), which funds and supports the HVTN – combines the strength of Merck’s vaccine research efforts and clinical trials expertise with the clinical trials experience and global capacity of the HVTN. The vaccine candidate used in this study has generated strong and durable cellular immune responses against HIV in early human trials. This collaboration could accelerate HIV vaccine development work by guiding scientific decisions for future HIV vaccine trials.
Proof of Concept
The trial is known as a ‘proof-of-concept’ study because it enables researchers to test the concept that the vaccine candidate prevents HIV infection, or results in lower HIV levels in the blood of those who become infected with HIV. If the concept is proven – that is, if data generated by the study show that the vaccine candidate provides some protection against HIV, or delays or diminishes the course of HIV infection – this information will guide future research.
“A proof-of-concept trial is designed to demonstrate the impact of a vaccine candidate on a disease but does not require the large number of participants and the resources required for a Phase III trial, which must enroll many thousands of participants” explains Lawrence Corey, M.D., principal investigator of the HVTN.
The collaborative trial is the first study specifically designed to test the ability of a Merck-developed adenoviral vector-based trivalent vaccine candidate to affect the clinical course of HIV infection. This vaccine candidate is designed to generate a cellular immune response, as opposed to the antibody response typical of most vaccines in use today. The trial is expected to provide vital data about the ability of this vaccine approach to either prevent infection with HIV, and/or to maintain a lower average viral load compared with placebo in individuals who may become infected with HIV during the course of the study.
Information from several different sources, including HIV drug studies and studies of HIV-infected individuals, suggests that maintaining a lower viral load may be associated with clinical benefits to patients. The study will also evaluate whether the investigational vaccine is generally well tolerated by study participants.
“This trial is a critical test of whether the cellular immune response to HIV-1 that is generated by Merck’s vaccine candidate is potent enough to impact infection with HIV,” said Jeffrey Chodakewitz, M.D., vice president, Clinical Research, at Merck. “We’re pleased to extend our ongoing relationship with the HVTN on this important next step in our HIV/AIDS vaccine research program.”
This is the second collaboration between Merck, whose scientists have been conducting research to develop an HIV/AIDS vaccine for nearly 20 years, and the HVTN, a global clinical trial network funded and supported by NIAID, one of the National Institutes of Health. Merck and the HVTN are already collaborating on a global clinical trial that is testing the tolerability and immunogenicity of an earlier version of Merck’s vaccine candidate. That study is ongoing in 18 cities around the world.
“This proof-of-concept study will involve the cooperation of scientists, government officials, and community leaders from many different countries, underscoring the global response necessary to move the science forward,” Dr. Corey added.
The multicenter, randomized, double-blind, placebo-controlled Phase II trial has begun enrolling volunteers. Additional study sites are awaiting approval, and will be announced as they are approved by their local Institutional Review Boards. The trial seeks to enroll approximately 1,500 male and female volunteers aged 18 to 45 of diverse racial groups who are at high risk for contracting HIV. All study participants will receive counselling about how to reduce their risk of HIV infection.
The study is testing a Merck vaccine candidate – known as the MRKAd5 HIV-1 gag/pol/nef, or trivalent, vaccine – that is based on adenovirus, a common cold virus that has been modified so that it cannot reproduce and cause a cold in humans. The adenovirus is used as a vector, or a delivery vehicle, to transport three synthetically produced HIV genes into the cells. The three HIV genes are known as gag, pol and nef. The delivery of these HIV genes into the cells stimulates the body to generate a potent cellular immune response to HIV, producing an army of killer cells (called T cells) that are programmed to recognize and kill cells infected with HIV. No live HIV is used in the production of the vaccine candidate, so the vaccine candidate cannot cause HIV infection or AIDS.
According to UNAIDS, nearly 40 million people were living with HIV in 2004. With more than 13,000 new HIV infections each day, 95 percent of which occur in developing countries, the global epidemic shows no sign of abating. UNAIDS has reported that a record 3.1 million people died of AIDS in 2004, the highest number for any year since the epidemic began. As with other infectious diseases, development of a vaccine is recognized as the best long-term hope to end the AIDS pandemic. Vaccines are a critical part of an integrated strategy to fight HIV infection, which also includes treatment and prevention.
Source: The HIV Vaccine Trials Network and Merck & Co., Inc.