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

NCT02282709 | Completed Phase 3 DMC

• 1 other identifier: Foundation_LiverR
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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. 1.Phenotype and function of blood leukocytes during treatment; frequency of HCV-specific T cells, NK cells and monocytes
2. 2.Gene expression levels of leukocyte populations before, during and after treatment
3. 3.Gene expression levels of the type I IFN signaling pathway on whole blood samples
4. 4.Serum cytokines levels using multiplex platforms

Conditions

Chronic Hepatitis C

Keywords

Immunity

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (3)

• Gene expression levels of the type I IFN signaling pathway on whole blood samples measured by multiplex

  1 year

• Gene expression levels of leukocyte populations before, during and after treatment measured by microarray

  2 years

• Serum cytokines levels using multiplex platforms LUMINEX -100

  1 year

Study Arms (1)

Daclatasvir and asunaprevir

EXPERIMENTAL

daclatasvir 60 mg once daily asunaprevir 100 mg BID

Drug: Daclatasvir; Drug: asunaprevir

Interventions

Daclatasvir DRUG

60 mg once daily

Daclatasvir and asunaprevir

asunaprevir DRUG

100 mg BID

Daclatasvir and asunaprevir

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Foundation for Liver Research: lead

Study Sites (1)

Erasmus Medical Center

Rotterdam, 3015 CE, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 26223768 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

daclatasvir; asunaprevir

Condition Hierarchy (Ancestors)

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

Study Officials

• Rob de Knegt, M.D.

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2014
• First Posted: November 4, 2014
• Study Start: February 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: October 19, 2015

Record last verified: 2015-10

Locations

NL (1)