GSK Doses First Patient in Phase 3 Study of RSV Vaccine Candidate

February 24, 2021 - GSK recently announced that the first patient has been dosed in a Phase 3 clinical program investigating the immunogenicity, safety, and reactogenicity of a RSV vaccine candidate for older adults. 

AReSVi 004 is a randomized, open-label Phase 3 study that will enroll nearly 1,650 adults 60 years and older to test the  long-term immune response up to three years following vaccination of the candidate, GSK3844766A.

The study is expected to conclude at the beginning of 2024, with interim results expected in the second half of 2022.

“RSV is one of the most significant remaining unmet medical needs for older adults, with 1 out of 6 infected with RSV requiring a hospitalization,” Emmanuel Hanon, senior vice president and head of vaccines research and development for GSK, said in the announcement. 

“The pre-fusion F antigen and our proprietary adjuvant system allowed us to induce a strong immune response, of both humoral and cellular components, to levels normally seen in healthy adults,” Hanon continued. 

The start of the Phase 3 program follows positive Phase 1 and Phase 2 results on safety, reactogenicity, and immunogenicity. The results showed that GSK3844766A elicited a robust humoral and cellular immunity compared with baseline one month after immunization. 

Specifically, there was a ten-fold increase of RSV-A neutralizing antibodies and over 12 times more RSVPreF3 IgG antibodies in the vaccine group, GSK said.

Overall, the Phase 1 and Phase 2 trial results showed that the vaccine candidate can evoke the immune system necessary for older adults to produce a similar level of antibodies as in young adults. The vaccine candidate was also able to restore the lower levels of pre-existing RSV-specific T-cells observed in older adults before vaccination to similar levels observed in younger adults.

This is crucial to protect vulnerable populations, GSK highlighted. 

GSK3844766A contains a recombinant subunit pre-fusion RSV antigen combined with GSK’s proprietary AS01 adjuvant, which is also be used in the company’s shingles vaccine. 

GSK stated that GSK3844766A is part of a broad portfolio of RSV vaccines in development, which includes maternal and pediatric vaccine candidates. 

GSK will begin a Phase 3 study investigating the safety and efficacy of its RSV vaccine candidate for maternal immunization, according to a December announcement. 

The double-blind Phase 3 study will enroll 10,000 pregnant women between the ages of 18 to 49 years to uncover if a single dose of the RSV maternal unadjuvanted vaccine candidate can prevent RSV-associated lower respiratory tract infections in newborn infants. 

Researchers will study the candidate in vaccinated mothers as well, with interim results anticipated by the second half of 2022. 

The Phase 2/3 study with the pediatric RSV candidate vaccine is ongoing.

According to GSK, there are nearly 33 million cases of RSV annually in children less than five years of age, with about 2 million hospitalized and approximately 120,000 dying each year from complications associated with the infection.

About half of these pediatric hospitalizations and deaths occur in infants less than six months of age.

Generally, all children in the US are infected with RSV by the time they are two years old. One to two out of every 100 children younger than six months of age with RSV infection may need to be hospitalized, according to the CDC. 

RSV-associated lower respiratory tract-diseases are estimated to cause around 360,000 hospitalizations and 24,000 deaths in older adults each year in developed countries.

Therefore, a second study, AReSVi 006, will investigate the efficacy of the vaccine candidate to help protect older adults against lower-respiratory tract disease due to RSV. The study is expected to start in the coming months. 

In total, the company will enroll over 10,000 participants in the Phase 3 program studying GSK3888550A in older adults.