Investigational Janssen HIV Vaccine Found to be Ineffective, Study Discontinued

Janssen, along with its global partners, announced it was discontinuing its phase 3 Mosaico study for their investigational HIV vaccine regimen after the results demonstrated that the regimen was not effective in preventing HIV infection compared to placebo among study participants.

“We are disappointed with this outcome and stand in solidarity with the people and communities vulnerable to and affected by HIV,” Penny Heaton, MD, Global Therapeutic Area Head, Vaccines, Janssen Research & Development, LLC, said in a statement.

The study’s independent Data and Safety Monitoring Board (DSMB) determined there were no safety issues identified. Based on the DSMB’s recommendation, the study will be discontinued. Participants are being notified of the findings, and further analyses of the study data are planned.

What the Data Says

The HPX3002/HVTN 706, or “Mosaico,” phase 3 clinical trial began in 2019 and involved 3,900 volunteers ages 18 to 60 years in Europe, North America and South America.

An investigational HIV vaccine regimen tested among men who have sex with men (MSM) and transgender people was safe but did not provide protection against HIV acquisition, an independent data and safety monitoring board (DSMB) has determined. Based on the DSMB’s recommendation, the study will be discontinued. Participants are being notified of the findings, and further analyses of the study data are planned.

Janssen Vaccines & Prevention B.V., part of the Janssen Pharmaceutical Companies of Johnson & Johnson, sponsored the Mosaico study with funding support from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The trial was conducted by the NIAID-funded HIV Vaccine Clinical Trials Network, based at the Fred Hutchinson Cancer Research Center in Seattle. The U.S. Army Medical Research and Development Command provided additional study support.

The experimental vaccine regimen was developed by Janssen. It was based on “mosaic” immunogens—vaccine components featuring elements of multiple HIV subtypes—with the goal of inducing immune responses against a wide variety of global HIV strains. The investigational vaccine regimen consisted of four injections over a year of Ad26.Mos4.HIV. This vaccine candidate uses a common-cold virus (adenovirus serotype 26, or Ad26) to deliver the mosaic immunogens. The final two vaccinations were accompanied by a bivalent (two-component) HIV envelope protein formulation, combining clade C gp140 and mosaic gp140 envelope proteins, adjuvanted by aluminum phosphate to boost immune responses. All study vaccinations were completed in October 2022.

The DSMB determined the number of HIV infections were equivalent between the vaccine and placebo arms of the study. During the clinical trial, all participants were offered comprehensive HIV prevention tools, including pre-exposure prophylaxis, or PrEP. Study staff ensured that participants who acquired HIV during the trial were promptly referred for medical care and treatment.

The Mosaico findings track with developments in the Phase 2b “Imbokodo” (HPX2008/HVTN 705) clinical trial, which was testing a similar HIV vaccine regimen in young women in sub-Saharan Africa. A DSMB determined in 2021 that the experimental vaccine regimen in that study was also safe but ineffective in protecting against HIV acquisition.

The study used a mosaic-based adenovirus serotype 26 vector (Ad26.Mos4.HIV) vaccine that administered during four vaccination visits over one year. A mix of soluble proteins (Clade C/Mosaic gp140, adjuvanted with aluminum phosphate) was also administered at visits three and four.