Role of the Host Immunity in the Non-response to Direct Anti-viral Agent (DAA) Therapy

NCT03155113 | Completed

• 1 other identifier: NR-DAA-HCV
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

Anti-viral, hepatitis C virus (HCV)-specific immune T cell responses are functionally defective in patients with chronic hepatitis C and this functional impairment is believed to contribute to virus persistence. Persistent exposure to high virus loads is likely involved in the pathogenesis of T cell dysfunction. The underlying hypothesis of the project is that the level of anti-viral immune dysfunction in chronic HCV infection is a causal factor which can influence non-response to therapy. Although the rate of response to direct anti-viral agent (DAA) therapy, in untreated, non-cirrhotic, patients is between 95% and 100%, however, the response rate is lower in specific subgroups of patients, including genotype 3 cirrhotics and patients with decompensated cirrhosis, irrespective of the infecting genotype. Aim of the present study will be thus to understand whether non-response to therapy is associated with a wider and deeper anti-viral immune dysfunction, by comparing individual HCV-specific T cell responses in two groups of responder and non-responder patients. Characterization of protective immunity in non-responder patients could allow to identify baseline predictors of non-response to therapy to be used in the daily clinical practice. Objective of the study will be to compare the features (intensity and quality) of the overall HCV-specific immune T cell response in patients non-responder and responder to DAA therapy. To achieve this goal, T lymphocytes (either CD4 or CD8) isolated from the peripheral blood of the patients, before starting DAA therapy, will be stimulated with HCV proteins to evaluate the capacity of those cells to expand, produce cytokines and express cytotoxic capacity.

Conditions

Chronic Hepatitis C

Keywords

Chronic infection; HCV; DAA therapy; immune response

Outcome Measures

Primary Outcomes (1)

• Immune T cell response

  Identification of specific baseline immunological features predictors of non-response to therapy

  between 12 and 14 months from the beginning of the study

Study Arms (1)

patients with chronic HCV infection

OTHER

Patients with chronic HCV infection to be treated with any of the available DAA (without associated PEG-IFN) in daily clinical practice. Intervention: Blood Drawing.Before starting therapy a blood sample will be collected from any subject.

Other: blood drawing

Interventions

blood drawing OTHER

Before starting therapy a blood sample will be collected from any subject.

patients with chronic HCV infection

Eligibility Criteria

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

You may qualify if:

• naïve HCV genotype 1 infected chronic patients (F3-F4 fibrosis stages by liver histology of fibroscan) treated with any of the available DAA (without associated PEG-IFN) in daily clinical practice:
• non-responder patients, enrolled and studied after identification of non-response (at least 12 weeks after end of therapy) - 50 patients
• responder patients, enrolled and studied before therapy - 25 patients
• male or female, age ≥ 18 years
• quantifiable plasma HCV-RNA
• F3-F4 liver fibrosis (Metavir) assessed by liver biopsy or by FibroScan™
• treatment with an optimal DAA schedule (based on EASL guidelines)
• evidence of adherence to therapy

You may not qualify if:

• Mixed genotype populations by deep HCV sequencing
• Non response following a non-optimal treatment schedule
• Signs or symptoms of HCC
• History of decompensated liver disease
• Co-infection with hepatitis B or HIV

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria di Parma: lead
• AbbVie: collaborator

Study Sites (1)

Unit of Infectious Diseases and Hepatology

Parma, 43126, Italy

Location

MeSH Terms

Conditions

Hepatitis C, Chronic; Persistent Infection

Interventions

Blood Specimen Collection

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

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Carlo Ferrari, Dr

  Università degli Studi di Parma

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: May 12, 2017
• First Posted: May 16, 2017
• Study Start: August 30, 2017
• Primary Completion: October 31, 2019
• Study Completion: December 31, 2019
• Last Updated: July 21, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)