NCT02774837

Tenofovir Versus Tenofovir + Telbivudine for Chronic Hepatitis B

Open Label Study of Nucleus(t)Ide Treated Patients Randomised to Tenofovir, or Tenofovir + Telbivudine

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 146 (actual)
• Sponsor: Seng Gee Lim · Academic / Other
• Sex: All
• Age: 21 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Chronic Hepatitis B is the most common cause of chronic viral liver disease worldwide afflicting 350 million persons, leading to significant morbidity and mortality due to liver disease and HCC in 20-40% of infected persons. With the advent of nucleoside analogues, this rescued patients with significant risk of disease progression, but in most circumstances, therapy was needed long term as HBsAg seroclearance was an uncommon occurrence, and stopping therapy was associated with relapse of disease and hepatitis B flares. The use of pegylated interferons showed increased HBeAg seroconversion and HBsAg seroclearance rates compared to nucleoside analogues , however combination nucleos(t)ide analogue therapy has been quite disappointing. However a recent showed that the combination of telbivudine and tenofovir in a response guided therapy design, had a remarkable 6% HBsAg seroclearance at week 52 in patients. Such results require further confirmation. There is currently an unmet need for the large number of patients on long term nucleoside analogue therapy who have not achieved HBeAg seroconversion or HBsAg seroclearance. Such patients are seeking alternatives to long term therapy hence an exploration of other therapeutic strategies is attractive. An additional benefit of telbivudine has been the surprising improvement in renal function and this study seeks to examine whether this can improve the renal impairment that may be seen with tenofovir. Our study proposes to examine if the combination of tenofovir and telbivudine can improve endpoints. Patients fulfilling inclusion and exclusion criteria will be randomized to tenofovir or tenofovir and telbivudine (1:1 ratio). The primary endpoint will be a qHBsAg reduction of \>1log at week 96, which may predict future HBsAg seroclearance, which is also a secondary endpoint. An additional primary endpoint is increase in eGFR in the combination arm compared to the monotherapy arm. The study aims to enroll 146 patients randomized 1:1 ratio (73:73) patients. Multivariate analysis will be performed of baseline and on-treatment factors that predict the primary outcome.

Detailed description

Each subject must sign and date a study-specific informed consent form (ICF) prior to their participation in any screening activities. Prospective subjects should be screened no more than 28 days prior to administration of the first dose of study drug on Day 1. Screening evaluations will be used to determine eligibility of each candidate for study enrollment. Subjects meeting all of the inclusion criteria and none of the exclusion criteria as determined during screening will be eligible for the study. Candidates who fail to meet eligibility criteria by screening evaluations may be re-screened one time. Eligible patients at the end of screening will be randomised in a 1:1 ratio to experimental (combination) arm versus control (mono therapy) arm. Randomisation will be performed by computer generated random codes (performed by Singapore Clinical Research Institute) with a masked allocation sequence. There will be no blinding of therapy and the study will be conducted as an open label study since the outcomes are objectively measurable. After randomisation patients will be monitored 12 weekly for the first 24 weeks, then every 24 weekly until the last visit at 96 weeks. At each visit, patients will have a clinical evaluation and have a panel of laboratory tests: * Hematology: Full blood count, prothrombin time and international normalized ratio * Chemistry: Sodium, potassium, creatinine, albumin, alkaline phosphatase, -aspartate transaminase, alanine transaminase, lactate dehydrogenase, total bilirubin, creatine phosphokinase, alphafetoprotein, * Urinalysis: Urine dipstick (Appearance, color, leucocytes, nitrite, urobilinogen, protein, PH, specific gravity, ketone, bilirubin and glucose). * Viral serology: HBeAg, anti-HBe, HBsAg, qHBsAg and anti-HBs

Conditions

• Chronic Hepatitis B

Interventions

Type	Name	Description
DRUG	Tenofovir disoproxil	Tenofovir disoproxil 300mg once daily for 96 weeks
DRUG	Telbivudine	Telbivudine oral tablets 600mg once daily for 96 weeks

Timeline

• Start date: 2016-04-01
• Primary completion: 2020-07-01
• Completion: 2020-07-01
• First posted: 2016-05-17
• Last updated: 2019-03-18

Locations

1 site across 1 country: Singapore