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Preliminary safety and efficacy of REP 2139-Mg or REP
2165-Mg used in combination with tenofovir disoproxil
fumarate and pegylated interferon alpha 2a in treatment
naïve Caucasian patients with chronic HBeAg negative
HBV infection
Michel Bazinet1, Victor Pantea2, Gheorghe Placinta2, Iurie
Moscalu3, Valentin Cebotarescu2, Lilia Cojuhari4, Paulina Jimbei4,
Liviu Iarovoi2, Valentina Smesnoi4, Tatiana Musteata4, Alina
Jucov2,3, Adalbert Krawczyk5, Andrew Vaillant1; 1Replicor Inc.,
Montreal, QC, Canada; 2Department of Infectious Diseases, Nicolae
Testemitanu State University of Medicine and Pharmacy, Chisinau,
Moldova (the Republic of); 3ARENSIA Exploratory Medicine,
Republican Clinical Hospital, Chisinau, Moldova (the Republic of);
4Toma Ciorba Infectious Clinical Hospital, Chisinau, Moldova (the
Republic of); 5Institute for Virology, University Hopsital at the University
of Duisburg-Essen, Essen, Germany
Nucleic acid polymers (NAPs) block HBsAg release from HBV
infected hepatocytes. The NAP 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
naïve patients with chronic HBeAg negative HBV infection.
Forty patients will receive 26 weeks of lead-in TDF (300mg PO
qD) followed by randomization (1:1) into experimental and
control groups. The experimental group will receive 48 weeks
of TDF, peg-IFN (180ug 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, University
Hospital at the University Duisburg-Essen, Essen, Germany.
Enrolment is complete and 22 patients have received ≥ 12
weeks of treatment in control and experimental groups. After
TDF lead-in, most patients have serum HBV DNA ≤ 10 IU / ml
prior to peg-INF exposure. Triple combination therapy is well
tolerated in all patients and 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 in all patients during TDF lead-in and in the
control group to date. In patients having completed 12 weeks
of NAP exposure, 4 /5 receiving REP 2139-Mg and 4 / 6
patients receiving REP 2165-Mg have experienced multilog
reductions in serum HBsAg and increases in serum anti-HBs.
Two patients in the REP 2139-Mg group experienced multilog
drops after only 4 weeks. An additional REP 2165-Mg patient
(a 5th responder in this group) has also experienced a multilog
HBsAg drop after 4 weeks of exposure. NAP-mediated HBsAg
reductions are accompanied by otherwise asymptomatic ALT /
AST / GGT flares substantially greater than those in the control
group. These preliminary data demonstrate 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.
Disclosures:
Michel Bazinet - Board Membership: Replicor Inc.; Employment: Replicor Inc.;
Management Position: Replicor Inc.; Patent Held/Filed: Replicor Inc.; Stock
Shareholder: Replicor Inc.
Andrew Vaillant - Employment: Replicor; Stock Shareholder: Replicor
The following people have nothing to disclose: Victor Pantea, Gheorghe Placinta,
Iurie Moscalu, Valentin Cebotarescu, Lilia Cojuhari, Paulina Jimbei, Liviu Iarovoi,
Valentina Smesnoi, Tatiana Musteata, Alina Jucov, Adalbert Krawczyk 作者: StephenW 时间: 2016-10-27 05:53