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OP116
Update on safety and efficacy in the REP 401 protocol: REP
2139-Mg or REP 2165-Mg used in combination with tenofovir
disoproxil fumarate and pegylated interferon alpha 2A
in treatment naı¨ve caucasian patients with chronic HBeAg
negative HBV infection
Michel Bazinet1, Victor Pantea2, Gheorghe Placinta2, Iurie
Moscalu3, Valentin Cebotarescu2, Lilia Cojuhari2, Pavlina
Jimbei4, Liviu Iarovoi2, Valentina Smesnoi4, Tatiana Musteata4,
Alina Jucov2,3, Adalbert Krawczyk5, Andrew Vaillant1
1Replicor Inc., Montre´al, Canada; 2Department of Infectious
Diseases, Nicolae, Testemitanu State University of Medicine and
Pharmacy, Testemitanu, Moldova; 3ARENSIA Exploratory Medicine,
Republican Clinical Hospital, Testemitanu, Moldova; 4Toma Ciorbaˇ
Infectious Clinical Hospital, Bucharest, Romania;
5Universita¨tsklinikum Essen, Institute for Virology, Essen, Germany
Background: The nucleic acid polymer REP 2139 clears serum
HBsAg in chronic HBV infection, improving the efficacy of
immunotherapy and facilitating establishment of functional control
off treatment. The REP 401 protocol (NCT02565719) is a randomized,
controlled trial assessing the safety and efficacy of REP 2139
and a REP 2139 derivative with improved clearance (REP 2165) in
combination with tenofovir disoproxil fumarate (TDF) and pegylated
interferon alpha 2a (peg-IFN) in treatment naı¨ve patients with chronic
HBeAg negative HBV infection.
Methods: Forty patients will receive 26 weeks of lead-in TDF
(300 mg PO qD) followed by randomization (1:1) into experimental
and control groups. The experimental group will receive 48 weeks of
TDF (300 mg PO qD), peg-IFN (180 lg SC qW) and REP 2139-Mg
or REP 2165-Mg (1:1, 250 mg IV infusion qW). Patients in the
control group will receive 48 weeks of TDF + peg-IFN but will
crossover to 48 weeks of experimental therapy in the absence of a 3
log drop in HBsAg after 24 weeks of peg-IFN. Serum viremia is
being monitored offsite at the Institute for Virology, Universita
¨tsklinikum Essen, Essen, Germany.
Result: Twenty-nine patients have received C12 weeks of treatment
in control and experimental groups. After TDF lead-in, most patients
have serum HBV DNA B10 IU/ml prior to peg-INF exposure. Triple
combination therapy is well tolerated in all patients. One patient
receiving REP 2165-Mg developed infusion reactions after the 20th
dose, otherwise no infusion reactions have been observed with either
NAP. Serum HBsAg reductions, increases in serum anti-HBs or
serum ALT/AST/GGT flares were negligible or absent during the
TDF lead-in and in all but 2 patients in the control groups to date. In
patients having completed 12 weeks of NAP exposure, 9/9 receiving
REP 2139-Mg and 6/9 patients receiving REP 2165-Mg have experienced[
1 log reductions in serum HBsAg. HBsAg reductions are[3
log in 7/9 REP 2139 patients and 4/9 REP 2165 patients. Increases in
serum anti-HBs are the most dramatic in these patients. NAP-mediated
HBsAg reductions are accompanied by otherwise asymptomatic
ALT/AST/GGT flares substantially greater than those in the control
group.
Conclusion: These updated preliminary data continue to confirm the
tolerability and efficacy of REP 2139 and REP 2165 when used in
combination with peg-IFN and TDF in patients with HBeAg negative
chronic HBV infection. Early clearance in serum HBsAg mediated by
NAPs is correlated with the onset of an intense transaminase flare and
suggests NAP-mediated HBsAg clearance improves the efficacy of
peg-IFN in this patient population.
Hepatol Int (2017) 11 (Suppl 1):S1–S1093 S85
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发表于 2017-2-11 22:58
