The AIDS Clinical Trials Group (ACTG), the largest global HIV research network, today announced the launch of A5355, a clinical trial studying a new cytomegalovirus (CMV) vaccine in adults with both HIV and CMV. The study will evaluate whether the new vaccine Triplex is safe and effective in eliciting a CMV-specific immune response in people living with HIV and is thus able to suppress CMV replication.
Almost everyone living with HIV is also living with CMV. There is strong evidence that living with both HIV and CMV is associated with chronic inflammation, which may be related to significant co-morbidities, including heart disease, strokes, neurological problems, and diabetes. Triplex is a modified vaccinia ankara (MVA)-based vaccine that encodes three full-length CMV antigens [pp65 (UL83), IE1-exon4 (UL123), and IE2-exon5 (UL122)]. Phase 1 and 2 studies conducted in more than 100 adults with hematologic stem cell transplants have demonstrated that Triplex is safe and can prevent CMV-related disease.
“Because almost all individuals living with HIV have also been exposed to CMV and they both persist across the lifetime, CMV is an important research focus as we seek to curtail the impact of other chronic diseases associated with HIV,” said ACTG chair Judith Currier, M.D., M.Sc., University of California, Los Angeles. “The ACTG is eager to gain insights from this first-of-its-kind study into Triplex’s potential ability to reduce systemic inflammation among people living with HIV, which can be linked to a number of health issues that impact their quality of life.”
A5355 is a phase 2, double-blind, randomized, placebo-controlled study evaluating the safety and immunogenicity of two injections of Triplex in adults aged 18 to 65 living with both HIV and CMV. Participants will be randomized in a 2:1 ratio, such that 60 will receive Triplex and 30 will receive placebo at study entry (day zero) and week four, both through two intramuscular deltoid injections. Participants will be followed for 92 weeks after the last scheduled vaccination at week four, for a total study duration of 96 weeks. At least 25 percent of participants will be cisgender or transgender women, and all must have undetectable HIV RNA on antiretroviral therapy (with current CD4+ cell count >250 cells/μL and nadir CD4+ cell count ≥100 cells/μL).
“We hope that improved control of asymptomatic CMV replication will decrease systemic markers of inflammation and eventually improve the lives of people with HIV worldwide,” said protocol chair Sara Gianella, M.D., University of California, San Diego (UCSD). “We are particularly excited that this study is making a dedicated effort to enroll cisgender and transgender women, who tend to be underrepresented in most HIV treatment studies.”
A5355 is led by Dr. Gianella and Davey Smith, M.D., USCD. City of Hope, a National Cancer Institute-designated comprehensive cancer center in southern California, developed Triplex. It is being supplied to study A5355 by City of Hope and Don Diamond, Ph.D., a City of Hope professor. Helocyte, Inc., a partner company of Fortress Biotech, Inc, is the exclusive worldwide licensee of Triplex.
About the ACTG
Founded in 1987, the AIDS Clinical Trials Group (ACTG) was the world’s first HIV research network. It is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), and collaborating NIH Institutes. The ACTG conducts groundbreaking studies to improve the treatment of HIV and its complications, including tuberculosis and viral hepatitis; reduce new infections and HIV-related illness; and advance new approaches to prevent, treat, and ultimately cure HIV in adults and children. More recently, The ACTG has expanded its focus to include the evaluation of outpatient treatments for COVID-19. ACTG investigators and research units in 15 countries serve as major resources for HIV/AIDS research, treatment, care, and training/education in their communities. ACTG studies have helped establish current paradigms for managing HIV disease, and have informed HIV treatment guidelines, resulting in dramatic decreases in HIV-related mortality worldwide.
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