Effect of ASV and DCV Therapy on the Quality of Immune Status in Chronic HCV Patients

Chronic Hepatitis C Clinical Trial

— ImmunoDual  

Official title:

Effect of ASV and DCV Therapy on the Quality of Immune Status in Chronic HCV Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02282709
• Other study ID #: Foundation_LiverR
• Status: Completed
• Phase: Phase 3
• First received: October 23, 2014
• Last updated: October 16, 2015
• Start date: February 2014
• Est. completion date: July 2015

Study information

• Verified date: October 2015
• Source: Foundation for Liver Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial Summary

Rationale: Chronic HCV infection is characterised by a weak HCV specific CD8+ T cell response, due to continuous pressure of high viral load. Treatment of chronic HCV patients with ASV and DCV will result in a significant drop in HCV viral load. At present, no information is available on the immunological effects of treatment with ASV and DCV, nor on the early effects of viral load reduction caused by a compound that is thought not to possess direct immunomodulatory effects. This information will be crucial for a better understanding of the mechanisms that may limit the effectiveness of treatment, occurrence of viral rebound or relapses during, at the end of treatment or during the follow up period.

Objective: To evaluate in detail the functionality of immune cells in blood in chronic HCV patients before, during and after treatment with ASV and DCV, in an IFN-free regimen.

Study design: This is an investigator-initiated single center open label study with one arm of 12 patients.

Study population: Adult chronic HCV patients with genotype 1b, who are previous non-responders to the treatment.

Intervention (if applicable): All patients will be treated with twice daily a 200 mg oASV and once daily a 60 mg DCV for 24 weeks.

Main study parameters/endpoints:

1. Phenotype and function of blood leukocytes during treatment; frequency of HCV-specific T cells, NK cells and monocytes

2. Gene expression levels of leukocyte populations before, during and after treatment

3. Gene expression levels of the type I IFN signaling pathway on whole blood samples

4. Serum cytokines levels using multiplex platforms

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Patients between 18 and 70 years of age, with a chronic hepatitis C - genotype 1b infection

• Patients are non-responders to previous treatment with peginterferon or conventional interferon plus ribavirin combination therapy

• High viral load (>400,000 IU/ml)

• Indication for antiviral therapy of hepatitis C according to current clinical guidelines

• Written informed consent

Exclusion Criteria:

• Decompensated cirrhosis (Child-Pugh Grade B or C)

• Hepatic imaging (ultrasound, CT or MRI) with the evidence of hepatocellular carcinoma within the last 3 months.

• Females who are pregnant or breast-feeding

• History or other evidence of severe illness, malignancy or any other condition which would make the patient, in the opinion of the investigators, unsuitable for the study

• Co-infections with human immunodeficiency virus (HIV) or Hepatitis B virus (HBV)

• Presence of contra-indications for antiviral therapy with ASV and DCV:

• Interfering substance abuse, such as high alcohol intake (indicator: 28 drinks/ week)

• Any exposure to NS3 protease inhibitors or NS5A polymerase inhibitors

• Treatment with peginterferon/ ribavirin within 6 months before start of therapy

• Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating and completing in the study

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Daclatasvir
60 mg once daily
• asunaprevir
100 mg BID

Locations

Country	Name	City	State
Netherlands	Erasmus Medical Center	Rotterdam

Sponsors (1)

Lead Sponsor	Collaborator
Foundation for Liver Research

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HCV-specific T cell phenotype and function (a composite measure of (I) HCV-specific T-cell frequency and (II) phenotypic expression of memory markers and (III) inhibitory receptor markers		1 year	No
Primary	NK cell phenotype and function (a composite measure of (I) NK cell frequency and (II) expression of activation and inhibitory markers (III) IFN-y production upon IL-12/IL-18 stimulation and (IV) Perforin granzyme production		1 year	No
Secondary	Gene expression levels of the type I IFN signaling pathway on whole blood samples measured by multiplex		1 year	No
Secondary	Gene expression levels of leukocyte populations before, during and after treatment measured by microarray		2 years	No
Secondary	Serum cytokines levels using multiplex platforms LUMINEX -100		1 year	No