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OP-02 Establishment of High Rates of Functional Cure of HBeAg
Negative Chronic HBV Infection with REP 2139-Mg Based
Combination Therapy: Ongoing Follow-up Results from the REP
401 Study
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., ., Montreal, Canada; 2Nicolae Testemiţanu State University of Medicine and Pharmacy,
Department of Infectious Diseases, Chișinău, Moldova; 3Arensia Exploratory Medicine, Republican
Clinical Hospital, Chișinău, Moldova; 4Toma Ciorbǎ Infectious Clinical Hospital, ., Chișinău, Moldova;
5Universitätsklinikum Essen, Institute for Virology, Essen, Germany
Email: [email protected]
Background and aims: The REP 401 study (NCT02565719) is assessing the safety and efficacy of
REP 2139-Mg (clinical lead) or REP 2165-Mg combined with tenofovir disoproxil fumarate (TDF) and
pegylated interferon α-2a (pegIFN) in Caucasian patients with HBeAg negative chronic HBV infection.
Method: Lead-in TDF therapy in 40 patients was followed by randomization into an experimental group
(48 weeks of TDF, pegIFN and REP 2139-Mg or REP 2165-Mg) or an adaptive control group (24 weeks
of TDF + pegIFN followed by cross over to 48 weeks of experimental therapy). All patients were
subsequently entered into a treatment-free follow-up scheduled for 48 weeks. Viremia is monitored on
the Abbott Architect and Realtime platforms.
Results: Baseline HBsAg was >1000 IU/ml in all patients and 14775.7 ± 9302 and 9018 ± 8743 IU/ml
in adaptive control and experimental groups. Therapy was well tolerated except for one withdrawal due
to pegIFN-related depression. Two additional participants withdrew where therapy was well tolerated.
Antiviral responses between REP 2139-Mg and REP 2165-Mg were indistinguishable and not related
to HBV genotype or HBsAg, ALT or fibrosis (Fibroscan) at baseline. Following the introduction of TDF,
HBV DNA was well controlled in all patients during therapy. Following the introduction of NAPs, HBsAg
reduction was >1 log in 36/40 patients and became <1 IU/ml in 28/40 and <0.05 IU/ml in 24/40
participants. Transaminase flares occurred in 38/40 patients and were correlated with reductions in
HBsAg, were self-resolving during therapy and not accompanied by any evidence of liver dysfunction.
Transaminase flares were especially pronounced (400-1748 U/L) in patients where HBsAg became <1
IU/ml and were accompanied by profound elevations in anti-HBs (up to 255, 055 mIU/ml).
As of the date of submission, treatment-free follow-up has been extended to 24 or 48 weeks in 34/40
patients completing treatment. Persistent and stable inactive chronic HBV (HBV DNA <2000 IU/ml with
normal ALT) is present in 15/34 (44%) of participants. An additional 14/34 (41%) participants have
functional cure (HBsAg and HBV DNA target not detected). Liver function has normalized in 94% of
patients (versus 47% at baseline) and median hepatic stiffness consistent with F0 ( ≤7kPa) is present
in 81% of patients (versus 52% at baseline).
Conclusion: A finite REP 2139-Mg based combination therapy with TDF and pegIFN is well tolerated
and results in a high proportion of patients achieving control of infection not requiring further therapy
under current guidelines. Transaminase flares appear therapeutic in nature and may reflect an immune
mediated clearance of infected hepatocytes essential in establishing persistent control of chronic HBV
infection
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发表于 2019-2-23 03:44