CastleVax Initiates Phase 2 Trial of Intranasal COVID-19 Vaccine Targeting Mucosal Immunity
Key Insights
CastleVax (search) has dosed the first participant in a Phase 2 clinical study of CVAX-01, an intranasal COVID-19 (search) vaccine candidate designed to elicit mucosal immunity and prevent breakthrough infections.
The study will enroll approximately 200 adults to evaluate safety, tolerability, and immunogenicity compared to FDA-approved mRNA vaccines, with participants followed for 6 months.
Preclinical studies demonstrated that the Newcastle Disease Virus (search)-vectored vaccine protected animals from SARS-CoV-2 (search) infection and blocked virus transmission through mucosal immune responses.
CastleVax (search), a clinical-stage biotechnology company, has announced the initiation of a Phase 2 clinical study for CVAX-01, its intranasal COVID-19 (search) vaccine candidate. The first participant was dosed in the study designed to evaluate the safety, tolerability, and both systemic and mucosal immunogenicity of the vaccine against an FDA-approved injectable mRNA-based COVID-19 vaccine.
Novel Approach Targets Mucosal Immunity
The Phase 2 trial represents a significant advancement in next-generation COVID-19 (search) vaccine development, focusing on mucosal immunity to prevent breakthrough infections and transmission. "This Phase 2 study represents a major step forward towards our goal to develop a next-generation COVID-19 booster vaccine capable of eliciting mucosal immunity and protecting against SARS-CoV-2 (search) breakthrough infection and transmission," said Michael A. Egan, Ph.D., Chief Executive Officer and Chief Scientific Officer of CastleVax (search).
The vaccine utilizes CastleVax (search)'s attenuated Newcastle Disease Virus (search) (NDV)-based platform, which was developed by scientists at the Icahn School of Medicine at Mount Sinai, including Peter Palese, Adolfo García-Sastre, Florian Krammer, and Weina Sun. The technology was subsequently licensed to CastleVax by Mount Sinai.
Promising Preclinical and Phase 1 Results
Previous preclinical studies demonstrated that intranasal delivery of CVAX-01 efficiently induced mucosal immune responses that protected animals from SARS-CoV-2 (search) infection and blocked virus transmission. The vaccine's clinical development has progressed through a completed Phase 1 clinical study (NCT05181709), where intranasal delivery was shown to be safe, well tolerated, and induced SARS-CoV-2 spike-specific mucosal immune responses in healthy adult volunteers.
Phase 2 Study Design and Population
The Phase 2 study aims to enroll approximately 200 adults representative of the U.S. population, including individuals at high risk for severe COVID-19 (search) and those aged 65 and older. All participants must have previously received an FDA-authorized COVID-19 vaccine. The study will follow participants for 6 months after vaccination to evaluate the effectiveness of intranasal delivery in enhancing systemic immune responses and stimulating mucosal immunity.
Vaccine Technology and Regulatory Status
CVAX-01 is a next-generation, live, attenuated, NDV-vectored COVID-19 (search) vaccine that expresses a stabilized SARS-CoV-2 spike protein (search) using HexaPro technology developed by Dr. Jason McLellan at The University of Texas at Austin. The vaccine has demonstrated an attractive safety profile and low reactogenicity in humans across several completed and ongoing Phase 1, 2, and 3 clinical trials.
Notably, both live and inactivated versions of the vaccine delivered by intramuscular administration have completed two Phase 3 immunobridging studies and received full regulatory approval in Thailand and Emergency Use Authorization in Mexico.
Platform Potential and Funding
Egan emphasized the broader implications of the trial, stating, "Importantly, we expect this Phase 2 trial to validate the potential of our NDV-based vaccine platform to elicit infection blocking mucosal immune responses, allowing for the development of next generation vaccines targeting a wide variety of diseases."
The project has received support from the New York State Biodefense Commercialization Fund. CastleVax (search) was launched in August 2022 by the Mount Sinai Health System as a clinical-stage vaccine research and development company focused on commercializing the NDV vaccine platform technology, with an initial emphasis on respiratory viruses.