No safety signals of concern for study participants
SEATTLE – (Aug. 31, 2021) – A primary analysis of an experimental HIV vaccine regimen being studied in a high-incidence population of young women in sub-Saharan Africa found the experimental vaccine did not provide sufficient protection against HIV infection. No significant safety concerns were identified, but because the vaccine regimen failed to meet the study’s primary endpoint, with results falling short of statistical significance, the Imbokodo study, also called HVTN 705/HPX2008, will be discontinued. Further analysis of the Imbokodo study is ongoing, and the study has provided enough data to progress with key immunological correlates research. Participants in this Phase 2b proof-of-concept study will be unblinded and will continue to be referred to high-quality treatment and care.
The analysis of the study was reviewed by an independent data and safety monitoring board (DSMB).
“The high rates of HIV acquisition seen in the Imbokodo study of young women in sub-Saharan Africa remind us that, despite great progress made in treatment and prevention, HIV remains a huge health challenge for the region,” said Glenda Gray, MBBCH, FCPaed (SA), Protocol Chair and Co-Principal Investigator and Director of HVTN Africa Programs and President & CEO of the South African Medical Research Council. “This underpins the need to apply the knowledge gained from this trial to continue to advance the pursuit of a global HIV vaccine.”
The development of a safe and effective HIV vaccine is critical for global health. In the 40 years since the virus was discovered, a vaccine has proved elusive because of the virus’ unique ability to attack and evade the immune system.
This study began in 2017, reached full enrollment in 2019, and completed vaccinations in June 2020. The study was evaluating the experimental regimen in approximately 2,600 women between ages 18 and 35 across five countries: Malawi, Mozambique, South Africa, Zambia and Zimbabwe. According to UNAIDS, women and girls accounted for 63% of all new HIV infections in this region in 2020.
The experimental vaccine consisted of an adenovirus containing four “mosaic” immunogens – called mosaic because they are designed to induce immune responses against multiple global HIV strains. The regimen included four doses of the mosaic Ad26 vaccine; the final two doses were given together with doses of an HIV protein called clade C gp140 mixed with an aluminum phosphate adjuvant to boost immune response. Different HIV subtypes, or clades, predominate in various geographic regions around the world. Clade C HIV is common in southern Africa, where the Imbokodo study was conducted.
In preclinical studies, regimens with mosaic-based vaccines elicited a strong immune response associated with protection against HIV in monkeys. Findings from two early-stage human clinical trials, called TRAVERSE and APPROACH, also suggested that these vaccines were well-tolerated and could generate anti-HIV responses in healthy adult volunteers, increasing hope for good results in the Imbokodo trial. The vaccine was initially developed by the laboratory of Dan H. Barouch, M.D., Ph.D., at Beth Israel Deaconness Medical Center and Co-Principal Investigator of the HVTN, together with Janssen and other partners.
“Despite the use of the Ad26 technology, which is effective for COVID-19, the Imbokodo study illustrates that HIV is a virus that requires a higher degree of immune response to achieve effective protection,” said Larry Corey, MD, Principal Investigator, HVTN Leadership Operations Center, which is based at Fred Hutchinson Cancer Research Center. “We hope the details from the trial will provide evidence for what level of immune responses are required to achieve an effective vaccine. The study team and entire HVTN operations program thanks everyone
who participated in this study, which will continue to provide important data to help drive forward the search for an HIV vaccine.”
The Imbokodo study was supported by a public-private partnership led by Janssen Vaccines & Prevention B.V.; the Bill & Melinda Gates Foundation; the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH); and the HIV Vaccine Trials Network (HVTN), headquartered at the Fred Hutchinson Cancer Research Center in Seattle. Additional partners providing support included the U.S. Army Medical Research and Development Command (USAMRDC), the Ragon Institute of Massachusetts General Hospital and Massachusetts Institute of Technology and Harvard University. The study was conducted at clinical sites coordinated by HVTN, and the South African Medical Research Council (SAMRC) helped to implement Imbokodo in South Africa.
The Imbokodo primary analysis occurred 24 months after the last participant had their first vaccination. The study’s primary endpoint was based on the difference in number of new HIV infections between the placebo and vaccine groups from month seven (one month after the third vaccination timepoint) through month 24. This data found that through 24 months of follow up, 63 participants who received placebo (4.32% incidence) compared to 51 participants who received active vaccine acquired HIV (3.61% incidence). This analysis demonstrated a vaccine efficacy of 25.2% (95% confidence interval of vaccine efficacy -10.5% to 49.3%). Further analysis of the results from the Imbokodo study is ongoing.
Although the Imbokodo study will not continue, another HIV vaccine trial is ongoing in a different population and in different areas of the world. The Phase 3 Mosaico study, or HVTN 706/HPX3002, is testing the safety and efficacy of an “optimized” experimental vaccine regimen that includes the same mosaic Ad26 priming immunogen but has an optimized booster regimen that includes a mosaic envelope plus a Clade C booster. This optimized booster gives higher and broader immune responses than the booster used in Imbokodo. Study participants are men who have sex with men (MSM) and transgender populations in North America, Latin America and Europe.
Drs. Gray and Corey said the Imbokodo research team will continue to analyze data from the study and publish complete findings to guide future investigations and vaccine development.
“The Imbokodo study provides valuable safety data on the mosaic Ad26 regimen as we move forward, but the disappointing efficacy results and the unabated HIV acquisition rates in women in sub-Saharan Africa – even during times of countrywide lockdowns – highlight the continuing importance of developing an effective HIV vaccine. With the Mosaico study in progress and other efforts underway, we remain committed to the fight against HIV and the enduring medical and social consequences of the 40-year pandemic of HIV.” Drs. Gray, Corey, and Barouch said.
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About Fred Hutchinson Cancer Research Center
At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek new and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS and other life-threatening diseases. Fred Hutch’s pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation’s first National Cancer Institute-funded cancer prevention research program, as well as the clinical coordinating center of the Women’s Health Initiative and the international headquarters of the NIAID-funded HIV Vaccine Trials Network (HVTN) and COVID-19 Prevention Network (CoVPN).
HIV Vaccine Trials Network (HVTN)