siRNA daplusiran/tomligisiran and DNA vaccine JNJ-64300535 in NA-suppressed chronic hepatitis B: the OSPREY study

OSPREY was a single-arm, open-label, phase 1b study that assessed whether reduction of viral antigens by the small-interfering RNA daplusiran/tomligisiran (DAP/TOM) could enhance HBV-specific T-cell and/or HBsAg responses to the DNA vaccine JNJ-64300535 (JNJ-0535) in participants with virologically suppressed, HBeAg-negative chronic hepatitis B. All participants received DAP/TOM (200 mg, Q4W) for 24 weeks and 4 doses of JNJ-0535 from Week (W)14 to W26. NA was given until W36 and continued to Follow-up W48, unless stopping criteria were met. Of 24 participants enrolled, 11 (45.8%) achieved the primary endpoint of ≥2 log 10 HBsAg reduction at W36. JNJ-0535 vaccination enhanced core/polymerase-specific T-cell responses in 22% of participants by W28, and 39% during follow-up. Seven participants stopped NA based on W36 results and had more polyfunctional CD4 T-cells targeting ≥2 HBV antigens and a greater mean reduction in HBsAg at Follow-up W48 versus those who continued NA (2.42 log 10 IU/mL vs 0.96 log 10 IU/mL).