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

NCT ID: NCT02282709

Last Updated: 2015-10-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2015-07-31

Brief 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

Conditions

Chronic Hepatitis C

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Daclatasvir and asunaprevir

daclatasvir 60 mg once daily asunaprevir 100 mg BID

Group Type: EXPERIMENTAL

Daclatasvir

Intervention Type: DRUG

60 mg once daily

asunaprevir

Intervention Type: DRUG

100 mg BID

Interventions

Daclatasvir

60 mg once daily

Intervention Type: DRUG

asunaprevir

100 mg BID

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Foundation for Liver Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rob de Knegt, M.D.

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Center

Locations

Erasmus Medical Center

Rotterdam, , Netherlands

Countries

Netherlands

References

Spaan M, van Oord G, Kreefft K, Hou J, Hansen BE, Janssen HL, de Knegt RJ, Boonstra A. Immunological Analysis During Interferon-Free Therapy for Chronic Hepatitis C Virus Infection Reveals Modulation of the Natural Killer Cell Compartment. J Infect Dis. 2016 Jan 15;213(2):216-23. doi: 10.1093/infdis/jiv391. Epub 2015 Jul 28.

Reference Type: DERIVED

PMID: 26223768 (View on PubMed)

Other Identifiers

Foundation_LiverR

Identifier Type: -

Identifier Source: org_study_id