Arcturus Therapeutics has announced the initiation of a Phase 1 clinical trial for ARCT-2304, also known as LUNAR-H5N1, a self-amplifying mRNA (sa-mRNA) vaccine candidate designed for active immunization against pandemic influenza caused by the H5N1 virus. The first participant was injected in December 2024.
The randomized, placebo-controlled Phase 1 trial (NCT06602531) is being conducted at multiple sites in the U.S. and aims to enroll approximately 200 healthy adults, with 120 participants aged 18-59 and 80 participants aged 60-80. Screening of study participants began in November 2024. The trial is fully funded by the Biomedical Advanced Research and Development Authority (BARDA).
Trial Objectives and Design
The primary objective of this initial clinical trial is to assess the safety and immune responses to three different dose levels and two different vaccination schedules of the ARCT-2304 vaccine. Immune responses will be measured using hemagglutination inhibition (HAI), virus microneutralization (MN), and neuraminidase enzyme-linked lectin assays (ELLA).
ARCT-2304 leverages Arcturus' proprietary LUNAR delivery and STARR mRNA platform technologies. The STARR mRNA technology has demonstrated the ability to elicit robust immune responses at very low dose levels, with extended persistence of neutralizing antibodies compared to conventional mRNA vaccines, in previous clinical trials. The LUNAR and STARR technologies have an established safety database from prior COVID-19 and seasonal influenza vaccine trials, involving over 20,000 participants and dose ranges from 1 to 20 mcg of mRNA.
Arcturus' Perspective
"Clinically validating our low-dose STARR mRNA technology in H5N1 flu is a crucial step towards pandemic preparedness," said Joseph Payne, President and CEO of Arcturus Therapeutics. "Our team is working diligently with our partners, BARDA and CSL, in the United States and globally in this effort."
About H5N1 Influenza
H5N1 influenza is a significant concern in animal health, having affected over 10,000 wild birds, nearly a thousand dairy cows, and over 130 million poultry to date. Increased H5N1 infections in animals have led to a rise in human infections, including confirmed severe cases and fatalities in the United States. Most confirmed human infections are linked to exposure of U.S. dairy and poultry workers to infected animals.
About ARCT-2304 (LUNAR-H5N1)
ARCT-2304, also known as LUNAR-H5N1, is a sa-mRNA vaccine candidate formulated with Arcturus' LUNAR delivery technology. The sa-mRNA vaccine candidate is designed to create multiple copies of mRNA within the host cell following intramuscular injection, enhancing the expression of haemagglutinin (HA) and neuraminidase (NA) antigens. This approach potentially allows for lower doses compared to conventional mRNA vaccines. The lyophilized vaccine formulation is stable in refrigerators, simplifying cold-chain storage and reducing distribution risks.
Interim Phase 1 data is expected in the second half of 2025.
