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

• ClinicalTrials.gov Identifier: NCT01098006
• Recruitment Status: Completed
• First Posted: April 2, 2010
• Results First Posted: December 18, 2017
• Last Update Posted: February 25, 2020
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Immunologic Tests	Other: Blood withdrawal	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 99 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Study in Adult Subjects With Chronic Hepatitis B Infection to Support the Development of Immunological Assays
• Actual Study Start Date: April 29, 2010
• Actual Primary Completion Date: February 20, 2012
• Actual Study Completion Date: February 20, 2012

Arms and Interventions

Arm	Intervention/treatment
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 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; 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 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 activee inflammation and varying degrees of liver fibbrosis.	Other: Blood withdrawal; 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.
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.	Other: Blood withdrawal; 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; 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.	Other: Blood withdrawal; 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.

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: 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.
2. Frequency of CD4+Foxp3- Expressing CD45RA and/or HLADR and/or ICOS and/or PD1 [ Time Frame: 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.
3. Frequency of CD4+Foxp3+ Expressing CD45RA and/or Glucocorticoid-induced Tumor Necrosis Factor Receptor-related Protein (GITR) and/or Proliferation Marker Ki67 [ Time Frame: 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.
4. Frequency of CD4+Foxp3- Expressing CD45RA and/or GITR and/or Ki67 [ Time Frame: 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.
5. Frequency of CD4+Foxp3+ Expressing CD45RA and/or, Chemokine (C-C Motif) Receptor 7 (CCR7) and/or CD62L [ Time Frame: 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.
6. Frequency of CD4+Foxp3- Expressing CD45RA and/or CCR7 and/or CD62L [ Time Frame: 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.
7. Frequency of CD4+Foxp3+ Expressing CD45RA and/or CD39 and/or Tumor Necrosis Factor Receptor 2 (TNFR2) [ Time Frame: 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.
8. Frequency of CD4+Foxp3- Expressing CD45RA and/or CD39 and/or TNFR2 [ Time Frame: 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.
9. Frequency of CD4+Foxp3+ Expressing CD45RA and/or CTLA4 and/or OX40 [ Time Frame: 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.
10. Frequency of CD4+Foxp3- Expressing CD45RA and/or CTLA4 and/or OX40 [ Time Frame: 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.
11. Frequency of HBs- and HBc-specific CD4+Foxp3+ Expressing CD69 and/or LAP in Fresh Samples [ Time Frame: 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.
12. Frequency of HBs- and HBc-specific CD4+Foxp3- Expressing CD69 and/or LAP in Fresh Samples [ Time Frame: 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.
13. Frequency of HBc-specific CD4+Foxp3+ Expressing CD69 and/or LAP in Frozen Samples [ Time Frame: 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 :

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

2. Frequency of Cluster of Differentiation 8 (CD8+) Expressing CD40-L and/or IFNg and/or IL-2 and/or IL-17 in Fresh Samples [ Time Frame: 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).

3. Frequency of CD4+ Expressing CD40-L and/or IFNg and/or IL-2 and/or IL-17 in Frozen Samples [ Time Frame: 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).

4. Frequency of CD8+ Expressing CD40-L and/or IFNg and/or IL-2 and/or IL-17 in Frozen Samples [ Time Frame: 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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Belgium

GSK Investigational Site

Brussels, Belgium, 1070

GSK Investigational Site

Bruxelles, Belgium, 1000

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01098006
• Other Study ID Numbers: 113854
• First Posted: April 2, 2010
• Results First Posted: December 18, 2017
• Last Update Posted: February 25, 2020
• Last Verified: February 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:

Immunological assays; Chronic hepatitis B

Additional relevant MeSH terms:

Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic; Infections; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Hepadnaviridae Infections; DNA Virus Infections