At least 1 dose of pegIFNλ will be identified which is safe, well tolerated, and efficacious
for the treatment of chronic hepatitis B virus infection (CHB)
Amendment 7, Part B Sub Study: The primary purpose of this amendment is to obtain
preliminary data on the safety of pegylated interferon Lambda (Lambda) when administered in
combination with Entecavir(ETV) to patients with hepatitis E antigen-positive
(HBeAg-positive) chronic hepatitis B(CHB) infection employing a sequential therapy approach
Part A: Proportion of subjects who achieve an hepatitis B virus Deoxyribonucleic acid levels (HBV DNA) < 50 IU/mL (approximately 300 copies/mL) using the Roche COBAS® TaqMan - High Pure System (HPS) assayPart A: Mean change from baseline in log10 HBV DNA levels over time (Proportion of subjects with Alanine amino transferase (ALT) normalization (≤ 1 x upper limit of normal (ULN))
Part A: Proportion of subjects with ALT normalization (≤ 1 x ULN)
Part A: Hepatitis E antigen (HBeAg) loss
Part A: HBeAg seroconversion
Part A: Mean change from baseline in log10 quantitative HBeAg levels over time
Part A: Number and percent of subjects with adverse events (AEs) or laboratory abnormalities
Part A: Number and percent of subjects with adverse events (AEs) or laboratory abnormalities
Part A: Pharmacokinetic (PK) parameter Maximum observed concentration (Cmax) of Pegylated interferon lambda (pegIFNλ) will be derived from serum concentration versus time data
Part A: Pharmacokinetic (PK) parameter Time of maximum observed concentration (Tmax) of Pegylated interferon lambda (pegIFNλ) will be derived from serum concentration versus time data
Part A: Pharmacokinetic (PK) parameter Trough serum concentration pre-dose (C0) of Pegylated interferon lambda (pegIFNλ) will be derived from serum concentration versus time data
Part A: PK parameter serum concentration 168 hours post observed dose [Cmin] (C0 will be used as an estimate of Cmin if sample is not collected) of pegIFNλ will be derived from serum concentration versus time data
Part A: PK parameter Area under the concentration-time curve in 1 dosing interval from time 0 to 168 hours post observed dose [AUC(TAU)] of pegIFNλ will be derived from serum concentration versus time data
Part A: PK parameter Accumulation index (AI) ratio of AUC(TAU) at steady-state to AUC(TAU) after the first dose (only conducted if data warrant) of pegIFNλ will be derived from serum concentration versus time data
Part B: HBeAg seroconversion rate at 24 weeks off treatment
Part B: Antiviral activity of Lambda/ETV regimen, as determined by the proportion of subjects who achieve an HBV DNA < 50 IU/mL (approximately 300 copies/mL) using the Roche COBAS® TaqMan - HPS assay
Part B: Mean change from baseline in HBV DNA over time in subjects treated with Lambda/ETV
Part B: HBeAg loss and seroconversion in subjects treated with Lambda/ETV regimen
Part B: HBeAg levels over time in subjects treated with Lambda/ETV regimen
Part B: biochemical response rates in subjects treated with Lambda/ETV regimen
Part B: Pharmacokinetic (PK) parameter Maximum observed concentration (Cmax) of Lambda/ETV regimen will be derived from serum concentration versus time data
Part B: Pharmacokinetic (PK) parameter Time of maximum observed concentration (Tmax) of Lambda/ETV regimen will be derived from serum concentration versus time data
Part B: Pharmacokinetic (PK) parameter Trough serum concentration pre-dose (C0) of Lambda/ETV regimen will be derived from serum concentration versus time data
Part B: PK parameter Area under the concentration-time curve in 1 dosing interval from time 0 to 168 hours post observed dose [AUC(TAU)] of Lambda/ETV regimen will be derived from serum concentration versus time data
Part B: PK parameter serum concentration 168 hours post observed dose [Cmin] (C0 will be used as an estimate of Cmin if sample is not collected) of Lambda/ETV regimen will be derived from serum concentration versus time data
Part B: PK parameter Accumulation index (AI) ratio of AUC(TAU) at steady-state to AUC(TAU) after the first dose (only conducted if data warrant) of Lambda/ETV regimen will be derived from serum concentration versus time data
Part B: Rate of resistance to ETV during treatment with the Lambda/ETV regimen
Minimum age: 18 Years.
Maximum age: 70 Years.
Gender(s): Both.
Local Institution, Clichy Cedex 92118, France
Local Institution, Nice Cedex 03 06202, France
Local Institution, Paris Cedex 12 75571, France
Local Institution, Rennes Cedex 9 35033, France
Local Institution, Frankfurt 60590, Germany
Local Institution, Freiburg 79106, Germany
Local Institution, Hamburg 20246, Germany
Local Institution, Hannover 30625, Germany
Local Institution, Tuebingen 72076, Germany
Local Institution, Hong Kong 852, Hong Kong
Local Institution, Shatin 30-32, Hong Kong
Local Institution, Tai Po 852, Hong Kong
Local Institution, Firenze 50012, Italy
Local Institution, Roma 00161, Italy
Local Institution, Chuncheon 200-704, Korea, Republic of
Local Institution, Gyeonggi-Do 480-717, Korea, Republic of
Local Institution, Seoul 120-752, Korea, Republic of
Local Institution, Seoul 135-710, Korea, Republic of
Local Institution, Seoul 135-720, Korea, Republic of
Local Institution, Seoul 138-736, Korea, Republic of
Local Institution, Rotterdam 3015 CE, Netherlands
Local Institution, Singapore 169608, Singapore
Local Institution, Singapore 119228, Singapore
Local Institution, Kaohsiung 807, Taiwan
Local Institution, Taichung 404, Taiwan
Local Institution, Tainan 704, Taiwan
Local Institution, Taipei 100, Taiwan
Local Institution, Taipei 114, Taiwan
Local Institution, Taoyuan 333, Taiwan
Heritage Medical Research Clinic, University Of Calgary, Calgary, Alberta T2N 4Z6, Canada
Advanced Clinical Research Institute, Anaheim, California 92801, United States
Sc Clinical Research, Inc., Garden Grove, California 92844, United States
University Of California, Davis Medical Center, Sacramento, California 95817, United States
Research And Education, Inc., San Diego, California 92105, United States
Yale New Haven Hospital, New Haven, Connecticut 06520, United States
Atlanta Gastroenterology Associates, Llc, Atlanta, Georgia 30308, United States
Local Institution, Winnipeg, Manitoba R3E 3P4, Canada
Mercy Medical Center, Baltimore, Maryland 21202, United States
Gastro Center Of Maryland, Colombia, Maryland 21045, United States
Local Institution, Camperdown, New South Wales 2050, Australia
Local Institution, Liverpool, New South Wales 2170, Australia
Local Institution, Westmead Nsw, New South Wales 2145, Australia
Medical Procare, Pllc, Flushing, New York 11355, United States
Office Of Sing Chan Md, Flushing, New York 11355, United States
Duke University Medical Center, Durham, North Carolina 27710, United States
Toronto General Hospital, Toronto, Ontario M5G 2C4, Canada
Toronto Western Hospital University Health Network, Toronto, Ontario M5T 2S8, Canada
Oregon Health & Science University, Portland, Oregon 97239, United States
University Of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, United States
Local Institution, Clayton Vic, Victoria 3168, Australia
Local Institution, Heidelberg Vic, Victoria 3084, Australia
Local Institution, Melbourne, Victoria 3004, Australia
Local Institution, Fremantle, Western Australia 6160, Australia