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Report for Clinical Trial NCT01639092

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Multicenter Randomized Controlled Open-label Trial of Tenofovir vs. Tenofovir Plus Entecavir in Chronic Hepatitis B Patients With Genotypic Resistance to Entecavir and Partial Virologic Response to Ongoing Treatment

With the availability of potent nucloes(t)ide analogues (NA), such as tenofovir disoproxil fumarate (TDF) and entecavir (ETV), suppression of serum HBV DNA to undetectable levels by polymerase chain reaction (PCR) assays became achievable in most NA treatment-naïve patients. Until recently, however, many patients commenced antiviral treatment with inferior NAs prior to the availability of TDF or ETV, such as lamivudine (LAM) which has a low genetic barrier to resistance. ETV resistance increase up to 51% of patients after 5 years of ETV treatment in lamivudine-refractory patients. Resistance to ETV appears to occur through a two-hit mechanism with initial selection of M204V/I mutation followed by amino acid substitutions at rtT184, rtS202, or rtM250. In vitro studies showed that ETV-resistant mutations are susceptible to TDF, but there are little clinical data on the efficacy of TDF monotherapy in patients with ETV-resistance. On the other hand, there was a retrospective cohort study reporting that, with the combination of TDF and ETV, most of patients became HBV DNA undetectable after median 6 months of treatment. Probability of reaching complete HBV DNA suppression was not decreased in patients with ADV or ETV-resistance. Thus, there is no consistent treatment recommendation for patients with ETV-resistance. In this clinical trial, the investigators will clarify whether tenofovir monotherapy is as effective as tenofovir plus entecavir in inducing complete virologic response in CHB patients with genotypic resistance to ETV and partial virologic response to ongoing treatment.

NCT01639092 Chronic Viral Hepatitis B Without Delta-agent
MeSH: Hepatitis A Hepatitis B Hepatitis B, Chronic Hepatitis
HPO: Hepatitis

3 Interventions

Name: Tenofovir

Description: Tenofovir 300mg Daily Oral

Type: Drug

Tenofovir monotherapy

Name: Tenofovir

Description: Tenofovir 300mg Daily Oral

Type: Drug

Tenofovir plus Entecavir combination

Name: Entecavir

Description: Entecavir 1 mg daily Oral

Type: Drug

Tenofovir plus Entecavir combination


Primary Outcomes

Description: The proportion of patients who achieve complete virologic response (serum HBV DNA concentrations below 15 IU/mL)

Measure: Proportion of patients with complete virologic response

Time: at week 48 of treatment

Secondary Outcomes

Description: Changes in serum HBV DNA levels during 48 weeks of treatment

Measure: Changes in serum HBV DNA levels

Time: at week 48, 96, 144, and 240 of treatment

Measure: Proportion of patients with normal ALT

Time: at week 48, 96, 144, and 240 of treatment

Measure: Proportion of patients with HBe-Ag loss or seroconversion

Time: at week 48, 96, 144, and 240 of treatment

Description: The proportion of patients with resistance mutations to Entecavir or Tenofovir at week 48

Measure: Proportion of patients with resistance mutations to Entecavir or Tenofovir

Time: at week 48, 96, 144, and 240 of treatment

Description: Virologic breakthrough is defined as the increase in serum HBV DNA by >1 log10 (10-fold) above nadir after achieving virologic response as determined by at least 2 consecutive measurements of at least 2 weeks apart, during continued treatment

Measure: Proportion of patients with virologic breakthrough

Time: at week 48, 96, 144, and 240 of treatment

Description: The proportion of patients who achieve complete virologic response (serum HBV DNA concentrations below 15 IU/mL)

Measure: Proportion of patients with complete virologic response

Time: at week 48, 96, 144, and 240 of treatment

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 M204V

Resistance to ETV appears to occur through a two-hit mechanism with initial selection of M204V/I mutation followed by amino acid substitutions at rtT184, rtS202, or rtM250. --- M204V ---



HPO Nodes


HPO:
Hepatitis
Genes 90
CD247 CTNNB1 ATP7B CASP10 PIEZO1 GUSB BLNK SHPK CYP7A1 IL17RA IGF2R CASP8 SH2D1A SLC25A15 BTK BTK C4B CD79B VPS33B XIAP SERPINA1 PIK3R1 GLIS3 POU2AF1 CIITA FOXP3 TPP2 RFX5 CIITA RASGRP1 RFXANK SLC25A15 AXIN1 TCF4 CD3D TP53 IL12A PRKCD CD40LG BTK IGHM IL17RC ALMS1 TRAF3IP2 KRT8 FAS LRRC8A FAS IL17F XIAP SPIB C1S RFX5 RFXAP MST1 TTC7A COG8 SKIV2L VIPAS39 IGLL1 PDGFRL TNFSF15 HSD3B7 CD3E AMACR ATP7B FASLG RFXANK IL12RB1 TCF3 CD79A KRT18 IRF5 MET PIK3CA MMEL1 ITCH TBX19 IL21R AIRE RFXAP TTC7A CLEC7A GPR35 ATP7A CYP7B1 STAT1 PGM1 APC TNPO3