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

NCT01098006 | Completed Results

• 1 other identifier: 113854
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Immunologic Tests

Keywords

Immunological assays; Chronic hepatitis B

Outcome Measures

Primary Outcomes (13)

• 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

  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 CD39 and/or Tumor Necrosis Factor Receptor 2 (TNFR2)

  The frequency was assessed based on the following range of markers: CD4, CD45RA, CD39, TNFR2 and anti-Foxp3.

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

• Frequency of CD4+Foxp3- Expressing CD45RA and/or CD39 and/or TNFR2

  The frequency was assessed based on the following range of markers: CD4, CD45RA, CD39, TNFR2 and anti-Foxp3.

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

• Frequency of CD4+Foxp3+ Expressing CD45RA and/or CTLA4 and/or OX40

  The frequency was assessed based on the following range of markers: CD4, CD45RA, CTLA4, OX40 and anti-Foxp3.

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

• Frequency of CD4+Foxp3- Expressing CD45RA and/or CTLA4 and/or OX40

  The frequency was assessed based on the following range of markers: CD4, CD45RA, CTLA4, OX40 and anti-Foxp3.

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

• Frequency of HBs- and HBc-specific CD4+Foxp3+ Expressing CD69 and/or LAP in Fresh Samples

  The frequency was assessed based on the following range of markers: CD4, CD69, LAP and anti-Foxp3.

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

• Frequency of HBs- and HBc-specific CD4+Foxp3- Expressing CD69 and/or LAP in Fresh Samples

  The frequency was assessed based on the following range of markers: CD4, CD69, LAP and anti-Foxp3.

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

• Frequency of HBc-specific CD4+Foxp3+ Expressing CD69 and/or LAP in Frozen Samples

  The frequency was assessed based on the following range of markers: CD4, CD69, LAP and anti-Foxp3.

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

Secondary Outcomes (4)

• 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)

• 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)

• 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)

• 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)

Study Arms (4)

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.

Other: Blood withdrawal

Interventions

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; HBeAg positive Group; Immune tolerant patients Group; Inactive carriers Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Brussels, 1000, Belgium

Location

GSK Investigational Site

Brussels, 1070, Belgium

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2010
• First Posted: April 2, 2010
• Study Start: April 29, 2010
• Primary Completion: February 20, 2012
• Study Completion: February 20, 2012
• Last Updated: February 25, 2020
• Results First Posted: December 18, 2017

Record last verified: 2020-02

Locations

BE (2)