PS-078
A phase 1b evaluation of HepTcell HBV-specific immunotherapy in
nuc-controlled, eAg negative chronic HBV infection
Young-Suk Lim2, David Mutimer3, Jeong Heo4, Won Young Tak5,
William Rosenberg6, Byoung Kuk Jang7, Yoon Jun Kim8, Dan Forton9,
Sybil Tasker10, Bertrand Georges11. 1Imperial College, London, United
Kingdom; 2Asan Medical Center, Seoul, Korea, Rep. of South; 3Queen
Elizabeth Medical Centre, Birmingham, United Kingdom; 4Pusan
National University, Busan, Korea, Rep. of South; 5Kyungpook National
University, Daegu, Korea, Rep. of South; 6Royal Free Hospital, London,
United Kingdom; 7Keimyung University Dongsan Medical Center, Daegu,
Korea, Rep. of South; 8Seoul National University, Seoul, Korea, Rep. of
South; 9St. George’s Hospital, London, United Kingdom; 10Altimmune,
Inc, Gaithersburg, MD, United States; 11Altimmune, Inc, London,
United Kingdom
Email: [email protected]
Background and aims: It iswell understood that cellular immunity is
key to HBV control. HepTcell is an immunotherapeutic syntheticproduct composed of 9 peptides designed to drive T cell-immune
responses against conserved regions of several HBV antigens. IC31® is
a TLR-9 agonist-based adjuvant formulation designed to minimize
systemic exposure.
Method: 60 HBeAg- subjectswell controlled on entecavir or tenofovir
were randomized to low and high dose peptides, with and without
IC31, placebo, and IC31 alone across 3 dose-escalating cohorts. All
subjects received 3 injections 28 days apart and were followed for 6
months after last injection. End points included patient and physician
assessment of reactogenicity, adverse events including changes in
transaminase levels, IFNγ-ELISpot of cultured PBMCs, and quantitative
HBsAg.
Results: All doses were well tolerated with no SAEs or liver flares.
The placebo group had higher baseline ELISpot responses, making
immunology results difficult to interpret, but after the 3 injections,
both adjuvanted peptide groups had increases in ELISpot spots/106
PBMC against the vaccine peptides compared to baseline values:
Low + IC31 = +5608 (95% CI 0, +17483); High+ IC31 = +4804 (95% CI
+2933, +10192); Placebo = +167 (95% CI −6717, +6692). Most of the
response was driven by peptides derived from HBV polymerase
antigen. Only one subject, a placebo recipient, had quantitative
HBsAg decline > 0.5 log.
Conclusion: HepTcell immunotherapywaswell tolerated and elicited
HBV-specific immune responses in patients with well controlled
HBeAg-negative chronic HBV. No effect on HBsAg was seen in this
short course monotherapy study, but the safety and immunogenicity
supports further evaluation in additional HBV populations and in
combination with other novel products. 作者: StephenW 时间: 2019-4-1 07:15