Bluejay Therapeutics has enrolled the first patient in its AZURE-2 global phase 3 clinical trial, marking a significant milestone in the development of brelovitug (BJT-778) for chronic hepatitis D (CHD). The randomized, controlled study will evaluate brelovitug monotherapy head-to-head against Hepcludex (bulevirtide) in adults with CHD, representing part of the company's global registrational program.
Trial Design and Endpoints
AZURE-2 will assess brelovitug administered as a 300 mg subcutaneous injection self-administered by participants weekly at home, compared with Hepcludex. The primary endpoint is the proportion of participants achieving a composite response at week 48, defined as undetectable hepatitis D virus RNA together with normalization of alanine aminotransferase (ALT). Elevated ALT levels serve as a marker of liver cell inflammation, which drives the development of liver cirrhosis and liver cancer.
"The primary endpoints of the AZURE-1 and AZURE-2 trials include a composite measure of viral response and ALT normalization," said Nancy Shulman, M.D., Chief Medical Officer of Bluejay Therapeutics. "Evidence from large cohort studies in hepatitis B has shown an association between delayed ALT normalization and increased risk of liver disease progression and liver cancer."
Addressing Critical Unmet Need
Chronic hepatitis D represents the most severe form of viral hepatitis, occurring as a coinfection in some people infected with hepatitis B virus. The disease affects approximately 7 million people globally and has the potential for rapid progression to liver cirrhosis, liver cancer and liver-related death. More than 50% of individuals with CHD are estimated to die of liver-related causes within 10 years of diagnosis.
"Chronic hepatitis D is the most severe form of viral hepatitis, yet it remains underserved, with limited or no approved treatment options in most countries," Shulman noted. Currently, there are no approved treatments for CHD in the United States and most countries worldwide.
Brelovitug Development Program
Brelovitug is an investigational, highly potent, pan-genotypic, fully human immunoglobulin G1 (IgG1) monoclonal antibody that targets the surface antigen (anti-HBsAg) on both hepatitis D virus (HDV) and hepatitis B virus (HBV). The drug is designed to neutralize and remove hepatitis B and hepatitis D virions and deplete HBsAg-containing subviral particles, potentially providing an advantageous safety profile.
In January 2025, brelovitug received FDA Breakthrough Therapy designation for CHD treatment. The drug has also received PRIME and Orphan designations from the European Medicines Agency. Beyond CHD, brelovitug has demonstrated immunomodulatory functions in chronic hepatitis B patients, which may help reconstitute antiviral immunity and contribute to functional cure when combined with other agents.
Concurrent Trial Progress
Enrollment continues on track for AZURE-1 (NCT06907290), a global pivotal clinical trial initiated in March 2025 that evaluates brelovitug efficacy and safety compared to delayed treatment. The AZURE-1 trial is powered to detect superiority of brelovitug treatment and is enrolling in the United States and other countries worldwide.
"Bluejay continues to swiftly advance our registrational program for brelovitug in CHD," said Keting Chu, M.D., Ph.D., Founder, Chief Executive Officer and Chairman of Bluejay Therapeutics. "We are proud to support the patients and providers in need of new hope."
