A Study in Adult Subjects With Chronic Hepatitis B Infect... | NCT01098006

NCT01098006

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Immune tolerant patients Group	Other	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.	Other: Blood withdrawal
HBeAg positive Group	Other	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.	Other: Blood withdrawal
Inactive carriers Group	Other	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.	Other: Blood withdrawal
HBeAg negative Group	Other	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.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Blood withdrawal	Other	A single blood sample was to be taken from all subjects at the study visit. No study-related treatment was given to the study participants.	HBeAg negative Group

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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	The frequency was assessed based on the following range of markers: CD4, CD45RA, ICOS, HLA-DR, PD-1 and anti-Foxp3.	At the time of the visit for each subject (i.e., Day 0)
Frequency of CD4+Foxp3- Expressing CD45RA and/or HLADR and/or ICOS and/or PD1	The frequency was assessed based on the following range of markers: CD4, CD45RA, ICOS, HLA-DR, PD-1 and anti-Foxp3.	At the time of the visit for each subject (i.e., Day 0)
Frequency of CD4+Foxp3+ Expressing CD45RA and/or Glucocorticoid-induced Tumor Necrosis Factor Receptor-related Protein (GITR) and/or Proliferation Marker Ki67	The frequency was assessed based on the following range of markers: CD4, CD45RA, GITR, anti-Foxp3 and Ki67.	At the time of the visit for each subject (i.e., Day 0)
Frequency of CD4+Foxp3- Expressing CD45RA and/or GITR and/or Ki67	The frequency was assessed based on the following range of markers: CD4, CD45RA, GITR, anti-Foxp3 and Ki67.	At the time of the visit for each subject (i.e., Day 0)
Frequency of CD4+Foxp3+ Expressing CD45RA and/or, Chemokine (C-C Motif) Receptor 7 (CCR7) and/or CD62L	The frequency was assessed based on the following range of markers: CD4, CD45RA, CCR7, CD62L and anti-Foxp3.	At the time of the visit for each subject (i.e., Day 0)
Frequency of CD4+Foxp3- Expressing CD45RA and/or CCR7 and/or CD62L

Secondary Outcomes

Measure	Description	Time Frame
Frequency of CD4+ Expressing CD40-L and/or Interferon-gamma (IFNg) and/or Interleukin 2 (IL-2) and/or IL-17 in Fresh Samples	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).

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Brussels		1000	Belgium
GSK Investigational Site

Arm/Group Information

ID	Title	Description
FG000	Immune Tolerant Patients Group	Immune tolerant patients aged between and including 18 and 65 years of age at study start, having high levels of hepatitis B virus (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.
FG001	HBeAg Positive Group	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 active inflammation and varying degrees of liver fibrosis.
FG002	Inactive Carriers Group	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.
FG003	HBeAg Negative Group	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.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Immune Tolerant Patients Group	Immune tolerant patients aged between and including 18 and 65 years of age at study start, having high levels of hepatitis B virus (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.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

The frequency was assessed based on the following range of markers: CD4, CD45RA, ICOS, HLA-DR, PD-1 and anti-Foxp3.

The analysis was performed on the According-to-protocol (ATP) cohort for immunogenicity, which included all subjects who met all eligibility criteria, with a blood sample available, who had satisfied all specific criteria according to their specific group and with data available for the markers analyzed within this outcome measure.

Posted

Median

Inter-Quartile Range

Treg cells/million cells

At the time of the visit for each subject (i.e., Day 0)

ID	Title	Description
OG000	Immune Tolerant Patients Group	Immune tolerant patients aged between and including 18 and 65 years of age at study start, having high levels of hepatitis B virus (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.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Immune Tolerant Patients Group	Immune tolerant patients aged between and including 18 and 65 years of age at study start, having high levels of hepatitis B virus (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.

ID	Term
D006509	Hepatitis B
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections