Inovio Pharmaceuticals has dosed the first participant with PENNVAX-GP in a randomized clinical trial that will assess its ability to drive remission of HIV infection.
This vaccine widely targets all major HIV strains and the potential to enhance the capacity of the immune system to eliminate or provide life-long control of HIV. This trial is part of a previously reported multi-year $6.95 million grant from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) to develop a single or combination therapy using Inovio’s PENNVAX-GP with the goal of attaining long-term HIV remission.
This Phase 1/2 HIV trial is a randomized, double-blinded, placebo-controlled study. The trial is divided into two cohorts and all vaccines are delivered via the CELLECTRA® device.
In the main study (Cohort A), 45 HIV-infected adults who initiated antiretroviral therapy during chronic infection will receive either PENNVAX-GP (containing HIV Gag/Pol/Env antigens), INO-6145 (containing HIV Gag/Pol antigens) or a placebo. Both vaccines are also co-administered with INO-9012 (IL-12 DNA immune activator). In the single arm and uncontrolled second study (Cohort B), individuals who initiated antiretroviral therapy during acute HIV infection will receive PENNVAX-GP + INO-9012.
The clinical trial’s principal investigator, and Professor of Medicine in Residence at the University of California, San Francisco, where the trial is being conducted, Steven G. Deeks said: “Although we do not expect this or any vaccine to be curative on its own, we firmly believe that a therapeutic vaccine will likely be needed as part of a combination approach. We and others in the field have been very impressed with what Inovio has accomplished in their vaccine against HPV, which shares some similarities with HIV, so we are optimistic.”
Kara W. Chew, MD, MS, Assistant Clinical Professor of Medicine and co-lead of the trial with Dr. Judith S. Currier at the collaborating University of California, Los Angeles, added, “We are excited to evaluate the potential of this vaccine to safely induce the broad HIV-specific immune responses likely needed to control HIV without antiretroviral therapy.”
Inovio president and CEO Joseph Kim said: “We have already demonstrated that PENNVAX-GP generated the highest overall levels of T cell and antibody immune response rates ever demonstrated by an HIV vaccine in healthy volunteers. Here, we are going after the Holy Grail of HIV treatment – investigating if our vaccine used alone or in combination with other therapies could bring true remission of HIV in patients.
“The key to this trial is that T cells generated by our vaccines target the body’s HIV reservoirs where the infection ‘hides’ from antiretroviral therapy. Inovio has already shown (in an HPV therapeutics trial) that our immunotherapy can generate sustained T cell responses which are able to traffic to an immunosuppressive tissue environment and eliminate virus-expressing cells. We expect results from this breakthrough study in late 2019.”
The primary objectives are to evaluate safety, tolerability and immunogenicity, with a secondary objective to determine PENNVAX-GP’s anti-reservoir activity in both cohorts. Study products will be administered at Day 0 and Weeks 4, 8 and 12. Participants will be observed on study for up to 64 weeks. Using standard and innovative measures of immunogenicity, we will determine the capacity of our vaccine strategies to stimulate broad, functional T cell responses against novel HIV epitopes, and comprehensively characterize the impact of the vaccine on several innate and adaptive immune parameters. The size of the active and latent reservoirs before and after vaccination will be measured.
Although current antiretroviral therapy can reduce the amount of circulating HIV in the blood to an undetectable level, latent cellular reservoirs of HIV continue to exist in the body such that when therapy is discontinued, these cells begin to produce HIV again. This proof-of-concept clinical program will test whether enhancing anti-HIV specific CD8 killer T cell immune responses alone or in combination with other products can influence the size of the viral reservoir pool, potentially resulting in reducing or eradicating the virus.
In May, PENNVAX-GP, in a Phase 1 trial (HVTN-098) in 94 HIV-negative volunteers, demonstrated durable and robust immune responses at month 12, a full six months after the last dose in the study. Inovio previously reported that PENNVAX-GP elicited the highest overall levels of immune response rates (cellular and humoral) ever demonstrated in a human study by an HIV vaccine.
To potentially prevent and treat HIV, PENNVAX-GP consists of a combination of three HIV antigens designed to generate both antibody and T cell responses and cover multiple global HIV strains. These clinical study results are being prepared for a manuscript to be submitted for a publication in a medical journal.