A Study in Adult Subjects With Chronic Hepatitis B Infection to Support the Development of Immunological Assays

Not Applicable

Completed

Conditions: Immunologic Tests

Interventions: Other: Blood withdrawal

Registration Number: NCT01098006

Lead Sponsor: GlaxoSmithKline

Brief Summary: The purpose of this study is to develop and characterize immunological assays on blood samples.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 99

Inclusion Criteria

Written informed consent obtained from the subject.
Subjects who the investigator believes that they can and will comply with the requirements of the protocol.
A male or female between, and including, 18 and 65 years of age at study start.
Evidence of chronic hepatitis B infection as per medical record.
Female subjects of non-childbearing potential may be enrolled in the study.
Female subjects of childbearing potential may be enrolled in the study, if the subject has practiced adequate contraception for 30 day prior to study start.

In addition to these general inclusion criteria, subjects should satisfy ALL specific criteria according to the specified group maximum 6 months prior to Visit 1 as per medical records:

Group A: Immune tolerant patients

Viral load: > 2x107 IU/mL of HBV DNA
HBeAg positive
Normal levels of ALT according to lab range Group B: HBeAg positive chronic hepatitis B patients
Viral load: > 2x104 IU/mL of HBV DNA
HBeAg positive
Increased levels of ALT and/or evidence of chronic hepatitis on liver biopsy Group C: Healthy carriers
Viral load: not exceeding 2x103 IU/mL of HBV DNA
HBeAg negative
Normal levels of ALT measured at least twice, at least 3 months apart, during the last 6 months Group D: HBeAg negative chronic hepatitis B patients
Viral load: > 2x103 IU/mL of HBV DNA
HBeAg negative
Increased levels of ALT and/or evidence of chronic hepatitis on liver biopsy

Exclusion Criteria

Any hepatitis B specific treatment prior to blood sampling at Visit 1.
Any known clinically significant anaemia or any other condition within 7 days prior to study entry (Visit 1) as per medical records that would preclude the drawing of blood as described in the protocol.
Receipt of live attenuated vaccines within 30 days preceding the blood sampling at Visit 1 and the administration of a pandemic influenza vaccine within 21 days preceding the blood sampling at Visit 1.
Receipt of blood products within 120 days prior to study entry (Visit 1).
Receipt of immunoglobulins within 120 days prior to study entry (Visit 1).
Receipt of interferon within 120 days prior to study entry (Visit 1).
Use of any investigational or non-registered product (drug or vaccine) within 30 days preceding study start, or planned use during the study period.
Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
History of immunosuppressive or immune-mediated disorders including autoimmune diseases, human immunodeficiency virus (HIV) infection and hepatitis C infection, based on medical history and physical examination (no laboratory testing required).
Pregnant or lactating female.
History of malignancy (unless there has been surgical excision followed by a sufficient observation period, of at least 5 years, to give a reasonable assurance of sustained cure and which, in the estimate of the investigator, is not likely to recur during the study period).
Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs (including chloroquine) within six months prior to the blood sampling at Visit 1 (for corticosteroids, this will mean prednisone ≥10 milligram/day (10 mg/day), or equivalent). Inhaled and topical steroids are allowed.
History of type I or type II diabetes mellitus including cases controlled with diet alone (a subject with past gestational diabetes is eligible).
History of major congenital defect.
Subjects with a history of, or current, alcohol or substance abuse.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HBeAg positive Group	Blood withdrawal	HBeAg positive chronic Hepatitis B patients aged between and including 18 and 65 years of age at study start, having elevated or fluctuating ALT levels, presence of HBeAg and variable HBV DNA on a high level, histology mainly with activee inflammation and varying degrees of liver fibbrosis.
Immune tolerant patients Group	Blood withdrawal	Immune tolerant patients aged between and including 18 and 65 years of age at study start, having high levels of hepatitis B viruss (HBV) replication characterized by elevated HBV DNA levels and presence of hepatitis B envelope antigen (HBeAg), but normal alanine aminotransferase (ALT) levels with normal or mild histology findings.
Inactive carriers Group	Blood withdrawal	Inactive carriers aged between and including 18 and 65 years of age at study start, having normal ALT levels, undetectable or low levels of serum HBV DNA; absence of HBeAg and presence of anti-HBe antibodies, histology with little or no inflammation and varying degrees of liver fibrosis.
HBeAg negative Group	Blood withdrawal	HBeAg negative chronic Hepatitis B patients aged between and including 18 and 65 years of age at study start, having absence of HBeAg, presence of anti-HBe, elevated ALT and HBV DNA levels, histology with significant inflammatory changes, liver fibrosis and cirrhosis.

Primary Outcome Measures

Name	Time	Method
Frequency of Cluster of Differentiation 4 (CD4) + Forkhead Box p3 (Foxp3) + Expressing CD45RA and/or Human Leucocyte Antigen DR Complex (HLA-DR) and/or Inducible T Cell Co-stimulator (ICOS) and/or PD1	At the time of the visit for each subject (i.e., Day 0)	The frequency was assessed based on the following range of markers: CD4, CD45RA, ICOS, HLA-DR, PD-1 and anti-Foxp3.
Frequency of CD4+Foxp3- Expressing CD45RA and/or CCR7 and/or CD62L	At the time of the visit for each subject (i.e., Day 0)	The frequency was assessed based on the following range of markers: CD4, CD45RA, CCR7, CD62L and anti-Foxp3.
Frequency of HBc-specific CD4+Foxp3+ Expressing CD69 and/or LAP in Frozen Samples	At the time of the visit for each subject (i.e., Day 0)	The frequency was assessed based on the following range of markers: CD4, CD69, LAP and anti-Foxp3.
Frequency of CD4+Foxp3- Expressing CD45RA and/or HLADR and/or ICOS and/or PD1	At the time of the visit for each subject (i.e., Day 0)	The frequency was assessed based on the following range of markers: CD4, CD45RA, ICOS, HLA-DR, PD-1 and anti-Foxp3.
Frequency of CD4+Foxp3- Expressing CD45RA and/or GITR and/or Ki67	At the time of the visit for each subject (i.e., Day 0)	The frequency was assessed based on the following range of markers: CD4, CD45RA, GITR, anti-Foxp3 and Ki67.
Frequency of CD4+Foxp3+ Expressing CD45RA and/or CD39 and/or Tumor Necrosis Factor Receptor 2 (TNFR2)	At the time of the visit for each subject (i.e., Day 0)	The frequency was assessed based on the following range of markers: CD4, CD45RA, CD39, TNFR2 and anti-Foxp3.
Frequency of CD4+Foxp3- Expressing CD45RA and/or CD39 and/or TNFR2	At the time of the visit for each subject (i.e., Day 0)	The frequency was assessed based on the following range of markers: CD4, CD45RA, CD39, TNFR2 and anti-Foxp3.
Frequency of HBs- and HBc-specific CD4+Foxp3- Expressing CD69 and/or LAP in Fresh Samples	At the time of the visit for each subject (i.e., Day 0)	The frequency was assessed based on the following range of markers: CD4, CD69, LAP and anti-Foxp3.
Frequency of CD4+Foxp3+ Expressing CD45RA and/or Glucocorticoid-induced Tumor Necrosis Factor Receptor-related Protein (GITR) and/or Proliferation Marker Ki67	At the time of the visit for each subject (i.e., Day 0)	The frequency was assessed based on the following range of markers: CD4, CD45RA, GITR, anti-Foxp3 and Ki67.
Frequency of CD4+Foxp3+ Expressing CD45RA and/or, Chemokine (C-C Motif) Receptor 7 (CCR7) and/or CD62L	At the time of the visit for each subject (i.e., Day 0)	The frequency was assessed based on the following range of markers: CD4, CD45RA, CCR7, CD62L and anti-Foxp3.
Frequency of CD4+Foxp3- Expressing CD45RA and/or CTLA4 and/or OX40	At the time of the visit for each subject (i.e., Day 0)	The frequency was assessed based on the following range of markers: CD4, CD45RA, CTLA4, OX40 and anti-Foxp3.
Frequency of CD4+Foxp3+ Expressing CD45RA and/or CTLA4 and/or OX40	At the time of the visit for each subject (i.e., Day 0)	The frequency was assessed based on the following range of markers: CD4, CD45RA, CTLA4, OX40 and anti-Foxp3.
Frequency of HBs- and HBc-specific CD4+Foxp3+ Expressing CD69 and/or LAP in Fresh Samples	At the time of the visit for each subject (i.e., Day 0)	The frequency was assessed based on the following range of markers: CD4, CD69, LAP and anti-Foxp3.

Secondary Outcome Measures

Name	Time	Method
Frequency of Cluster of Differentiation 8 (CD8+) Expressing CD40-L and/or IFNg and/or IL-2 and/or IL-17 in Fresh Samples	At the time of the visit for each subject (i.e., Day 0)	The frequency was assessed based on the following range of markers: CD8, CD40-L, IFNg, IL-2 and IL-17. Note: The precision of the measure (i.e., four decimals) of median and inter-quartile range is not sufficient to distinguish between the values median, lower and upper limits of inter-quartile range for some of the data presented within the table below (e.g., median=0.0001 and inter-quartile range=0.0001 to 0.0001).
Frequency of CD8+ Expressing CD40-L and/or IFNg and/or IL-2 and/or IL-17 in Frozen Samples	At the time of the visit for each subject (i.e., Day 0)	The frequency was assessed based on the following range of markers: CD8, CD40L, IFNg, IL-2 and IL-17. Note: The precision of the measure (i.e., four decimals) of median and inter-quartile range is not sufficient to distinguish between the values median, lower and upper limits of inter-quartile range for some of the data presented within the table below (e.g., median=0.0001 and inter-quartile range=0.0001 to 0.0001).
Frequency of CD4+ Expressing CD40-L and/or Interferon-gamma (IFNg) and/or Interleukin 2 (IL-2) and/or IL-17 in Fresh Samples	At the time of the visit for each subject (i.e., Day 0)	The frequency was assessed based on the following range of markers: CD4, CD40-L, IFNg, IL-2 and IL-17. Note: The precision of the measure (i.e., four decimals) of median and inter-quartile range is not sufficient to distinguish between the values median, lower and upper limits of inter-quartile range for some of the data presented within the table below (e.g., median=0.0001 and inter-quartile range=0.0001 to 0.0001).
Frequency of CD4+ Expressing CD40-L and/or IFNg and/or IL-2 and/or IL-17 in Frozen Samples	At the time of the visit for each subject (i.e., Day 0)	The frequency was assessed based on the following range of markers: CD4, CD40-L, IFNg, IL-2 and IL-17. Note: The precision of the measure (i.e., four decimals) of median and inter-quartile range is not sufficient to distinguish between the values median, lower and upper limits of inter-quartile range for some of the data presented within the table below (e.g., median=0.0001 and inter-quartile range=0.0001 to 0.0001).