HVTN, Partners Review Phase II Trial Data
HVTN 203 confirms product safety, but immune response data not sufficient to qualify for next phase trial
SEATTLE - Investigators and major collaborators of the HIV Vaccine Trials Network (HVTN) met yesterday to review data and discuss further plans regarding HVTN 203, a trial to test a prime boost strategy combining Aventis Pasteur’s ALVAC-HIV (vCP1452) and VaxGen’s AIDSVAX B/B. The data confirmed the safety of this combination, which is being used in other trials in the United States and abroad, and set the stage for discussions of how this vaccine combination may be further evaluated.
Based on the data, the HVTN investigators, in consultation with the National Institute of Allergy and Infectious Diseases (NIAID), Aventis Pasteur and VaxGen, determined not to pursue HVTN 501, a planned Phase III trial to test how participants’ immune responses would correlate to protection from HIV-1 infection. The ALVAC and AIDSVAX vaccines met the safety requirements to move forward to further trials, but data indicate that the ALVAC product did not induce a sufficient CD8 T cell immune response in participants to qualify for the next trial phase. Data regarding the antibody response induced by AIDSVAX has not yet been reviewed, but in earlier trials the product elicited an antibody immune response in most participants.
HVTN 203 was designed to determine what levels of CD8+ T cell response could be achieved in participants and if the frequency of such responses was high enough for a Phase III trial designed to define whether a vaccine-induced CD8+ T cell response could protect against HIV-1 infection. HVTN 203 also sought to identify what dose and schedule of the two vaccines, alone and in combination, would best achieve these levels. The ALVAC-HIV (vCP1542) vaccine did elicit an immune response and behaved similarly to other ALVAC vaccines.
“The data indicate that the T cell responses do not meet the stringent standards of the HVTN 501 trial design,” said Dr. Larry Corey, principal investigator for the HVTN. “We hope to continue testing this and other ALVAC vaccines to determine whether they are more immunogenic in different doses, in different populations, and in combination with other candidate HIV vaccines. The canarypox vector did demonstrate significant immunogenicity compared to placebo injections. However, the criteria that were established to move forward to a trial that would determine if CD8 T cell responses were associated with reducing the risk of acquiring HIV were not achieved.”
“HVTN 203 had many goals,” said Dr. Barney Graham, the protocol chair. “One was to determine CD8+ T cell response rates and whether they were sufficient to qualify for 501 trial design. Others goals, including safety, were satisfied, or are still being evaluated. Discussion is underway to determine whether alternative trial designs would help evaluate the vaccines’ effectiveness.”
The HVTN is conducting other trials of this vaccine combination in the United States and abroad. HVTN 039 is a Phase I trial evaluating the safety, tolerability and immunogenicity of a higher dose of ALVAC-HIV (vCP 1452) among populations in 10 U.S. cities. HVTN 026 is a Phase II trial testing the immunogenicity of ALVAC-HIV (vCP1452) alone and combined with AIDSVAX among populations in Brazil, Haiti, Peru, and Trinidad and Tobago.
“The goals of HVTN 026 are as important as before and are not affected by these results,” said Dr. Mauro Schechter, principal investigator for the HVTN site in Brazil.
Dr. Courtenay Bartholomew, principal investigator of the HVTN site in Trinidad, agreed with Dr. Schechter’s assessment.
“Particularly given the safety record observed in trials to date with these candidate vaccines, the objectives of HVTN 026 remain important,” Dr. Bartholomew said.
HVTN 026 will answer important scientific questions about the applicability of trial results in a North American population to populations elsewhere in the world. HVTN 039 will determine whether a higher dose of the product will elicit an even higher immune response in participants.
International investigators will continue to review the HVTN 203 data and consult with their colleagues, communities and volunteers before determining how to proceed with their trials.