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

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

April 1, 2010
April 2, 2010
May 24, 2017
December 18, 2017
December 18, 2017
April 29, 2010
February 20, 2012   (Final data collection date for primary outcome measure)
  • Frequency of Cluster of Differentiation 4 (CD4) + Foxhead 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 Day 0 ]
    The frequency was assessed based on the following range of markers: CD4, CD25, CD45RA, CD45RO, ICOS, CD39, tumor necrosis factor receptor 2 (TNFR2), HLA-DR, PD-1, chemokine receptor 7 (CCR7), CD62L, OX40, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), anti-Foxp3 and Ki67.
  • Frequency of CD4+Foxp3- Expressing CD45RA and/or HLADR and/or ICOS and/or PD1. [ Time Frame: At Day 0 ]
    The frequency was assessed based on the following range of markers: CD4, CD25, CD45RA, CD45RO, ICOS, CD39, tumor necrosis factor receptor 2 (TNFR2), HLA-DR, PD-1, chemokine receptor 7 (CCR7), CD62L, OX40, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), anti-Foxp3 and Ki67.
  • Frequency of CD4+Foxp3+ Expressing CD45RA and/or GITR and/or Ki67. [ Time Frame: At Day 0 ]
    The frequency was assessed based on the following range of markers: CD4, CD25, CD45RA, CD45RO, ICOS, CD39, tumor necrosis factor receptor 2 (TNFR2), HLA-DR, PD-1, chemokine receptor 7 (CCR7), CD62L, OX40, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), anti-Foxp3 and Ki67.
  • Frequency of CD4+Foxp3- Expressing CD45RA and/or GITR and/or Ki67. [ Time Frame: At Day 0 ]
    The frequency was assessed based on the following range of markers: CD4, CD25, CD45RA, CD45RO, ICOS, CD39, tumor necrosis factor receptor 2 (TNFR2), HLA-DR, PD-1, chemokine receptor 7 (CCR7), CD62L, OX40, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), anti-Foxp3 and Ki67.
  • Frequency of CD4+Foxp3+ Expressing CD45RA and/or CCR7 and/or CD62L. [ Time Frame: At Day 0 ]
    The frequency was assessed based on the following range of markers: CD4, CD25, CD45RA, CD45RO, ICOS, CD39, tumor necrosis factor receptor 2 (TNFR2), HLA-DR, PD-1, chemokine receptor 7 (CCR7), CD62L, OX40, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), anti-Foxp3 and Ki67.
  • Frequency of CD4+Foxp3- Expressing CD45RA and/or CCR7 and/or CD62L. [ Time Frame: At Day 0 ]
    The frequency was assessed based on the following range of markers: CD4, CD25, CD45RA, CD45RO, ICOS, CD39, tumor necrosis factor receptor 2 (TNFR2), HLA-DR, PD-1, chemokine receptor 7 (CCR7), CD62L, OX40, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), anti-Foxp3 and Ki67.
  • Frequency of CD4+Foxp3+ Expressing CD45RA and/or CD39 and/or TNFR2. [ Time Frame: At Day 0 ]
    The frequency was assessed based on the following range of markers: CD4, CD25, CD45RA, CD45RO, ICOS, CD39, tumor necrosis factor receptor 2 (TNFR2), HLA-DR, PD-1, chemokine receptor 7 (CCR7), CD62L, OX40, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), anti-Foxp3 and Ki67.
  • Frequency of CD4+Foxp3- Expressing CD45RA and/or CD39 and/or TNFR2. [ Time Frame: At Day 0 ]
    The frequency was assessed based on the following range of markers: CD4, CD25, CD45RA, CD45RO, ICOS, CD39, tumor necrosis factor receptor 2 (TNFR2), HLA-DR, PD-1, chemokine receptor 7 (CCR7), CD62L, OX40, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), anti-Foxp3 and Ki67.
  • Frequency of CD4+Foxp3+ Expressing CD45RA and/or CTLA4 and/or OX40. [ Time Frame: At Day 0 ]
    The frequency was assessed based on the following range of markers: CD4, CD25, CD45RA, CD45RO, ICOS, CD39, tumor necrosis factor receptor 2 (TNFR2), HLA-DR, PD-1, chemokine receptor 7 (CCR7), CD62L, OX40, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), anti-Foxp3 and Ki67.
  • Frequency of CD4+Foxp3- Expressing CD45RA and/or CTLA4 and/or OX40. [ Time Frame: At Day 0 ]
    The frequency was assessed based on the following range of markers: CD4, CD25, CD45RA, CD45RO, ICOS, CD39, tumor necrosis factor receptor 2 (TNFR2), HLA-DR, PD-1, chemokine receptor 7 (CCR7), CD62L, OX40, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), anti-Foxp3 and Ki67.
  • Frequency of HBs- and HBc-specific CD4+Foxp3+ Expressing CD69 and/or LAP in Fresh Samples. [ Time Frame: At Day 0 ]
    The frequency was assessed based on the following range of markers: CD4, CD25, CD45RA, CD45RO, ICOS, CD39, tumor necrosis factor receptor 2 (TNFR2), HLA-DR, PD-1, chemokine receptor 7 (CCR7), CD62L, OX40, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), anti-Foxp3 and Ki67.
  • Frequency of HBs- and HBc-specific CD4+Foxp3- Expressing CD69 and/or LAP in Fresh Samples. [ Time Frame: At Day 0 ]
    The frequency was assessed based on the following range of markers: CD4, CD25, CD45RA, CD45RO, ICOS, CD39, tumor necrosis factor receptor 2 (TNFR2), HLA-DR, PD-1, chemokine receptor 7 (CCR7), CD62L, OX40, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), anti-Foxp3 and Ki67.
  • Frequency of HBc-specific CD4+Foxp3+ Expressing CD69 and/or LAP in Frozen Samples. [ Time Frame: At Day 0 ]
    The frequency was assessed based on the following range of markers: CD4, CD25, CD45RA, CD45RO, ICOS, CD39, tumor necrosis factor receptor 2 (TNFR2), HLA-DR, PD-1, chemokine receptor 7 (CCR7), CD62L, OX40, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), anti-Foxp3 and Ki67.
  • Frequency of Hepatitis B (HB) antigen-specific regulatory T (Treg) cells. [ Time Frame: At Day 1 ]
  • Presence of HB antigen-specific Treg cells in cryopreserved and fresh blood samples from the same donor. [ Time Frame: At Day 1 ]
Complete list of historical versions of study NCT01098006 on ClinicalTrials.gov Archive Site
  • Frequency of CD4+ Expressing CD40-L and/or IFNg and/or Interleukin Receptor 2 (IL-2) and/or IL-17 in Fresh Samples. [ Time Frame: At Day 0 ]
    The frequency was assessed based on the following range of markers: CD4, CD25, CD45RA, CD45RO, ICOS, CD39, tumor necrosis factor receptor 2 (TNFR2), HLA-DR, PD-1, chemokine receptor 7 (CCR7), CD62L, OX40, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), anti-Foxp3 and Ki67.
  • Frequency of CD8+ Expressing CD40-L and/or IFNg and/or IL-2 and/or IL-17 in Fresh Samples. [ Time Frame: At Day 0 ]
    The frequency was assessed based on the following range of markers: CD4, CD25, CD45RA, CD45RO, ICOS, CD39, tumor necrosis factor receptor 2 (TNFR2), HLA-DR, PD-1, chemokine receptor 7 (CCR7), CD62L, OX40, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), anti-Foxp3 and Ki67.
  • Frequency of CD4+ Expressing CD40-L and/or IFNg and/or IL-2 and/or IL-17 in Frozen Samples. [ Time Frame: At Day 0 ]
    The frequency was assessed based on the following range of markers: CD4, CD25, CD45RA, CD45RO, ICOS, CD39, tumor necrosis factor receptor 2 (TNFR2), HLA-DR, PD-1, chemokine receptor 7 (CCR7), CD62L, OX40, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), anti-Foxp3 and Ki67.
  • Frequency of CD8+ Expressing CD40-L and/or IFNg and/or IL-2 and/or IL-17 in Frozen Samples. [ Time Frame: At Day 0 ]
    The frequency was assessed based on the following range of markers: CD4, CD25, CD45RA, CD45RO, ICOS, CD39, tumor necrosis factor receptor 2 (TNFR2), HLA-DR, PD-1, chemokine receptor 7 (CCR7), CD62L, OX40, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), anti-Foxp3 and Ki67.
  • Frequency of IL-17 positive T-cells. [ Time Frame: At Day 1 ]
  • Frequency of Th1 positive T-cells. [ Time Frame: At Day 1 ]
Not Provided
Not Provided
 
A Study in Adult Subjects With Chronic Hepatitis B Infection to Support the Development of Immunological Assays
A Study in Adult Subjects With Chronic Hepatitis B Infection to Support the Development of Immunological Assays
The purpose of this study is to develop and characterize immunological assays on blood samples.

Chronic hepatitis B patients of the following 4 groups will be asked to participate in the study:

  • Group A: Immune tolerant patients
  • Group B: Hepatitis B envelope antigen (HBeAg)-positive chronic hepatitis B patients
  • Group C: Healthy carriers
  • Group D: Hepatitis B envelope antigen (HBeAg)-negative chronic hepatitis B patients
Interventional
Not Applicable
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Immunologic Tests
Other: Blood withdrawal
Blood sampling
  • Group 1
    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.
    Intervention: Other: Blood withdrawal
  • Group 2
    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.
    Intervention: Other: Blood withdrawal
  • Group 3
    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.
    Intervention: Other: Blood withdrawal
  • Group 4
    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.
    Intervention: Other: Blood withdrawal
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
99
80
February 20, 2012
February 20, 2012   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years to 65 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
Belgium
 
 
NCT01098006
113854
Not Provided
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Not Provided
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP