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Evaluating the Role of Immune Responses in the Emergence of Protease Inhibitor Mutations

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Mohamed Tarek Shata, University of Cincinnati
ClinicalTrials.gov Identifier:
NCT01517529
First received: January 20, 2012
Last updated: October 20, 2015
Last verified: October 2015
History of Changes
  Purpose
The major goal of this project is to identify the role of the immune responses in the emergence of protease inhibitor mutants during therapy.

Condition
Hepatitis C

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Evaluating the Role of the Immune Responses in the Emergence of HCV NS3 Resistance Mutations During Protease Inhibitor Therapy

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Cincinnati:

Primary Outcome Measures:
  • Number of Participants Who Completed Standard Treatment [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
    Blood samples will be drawn while the subject is on treatment to measure viral load and HCV-specific immune responses.


Secondary Outcome Measures:
  • Number of Participants Who Cleared the Virus [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    Blood samples will be drawn while the subject is on treatment to measure viral load and HCV-specific immune responses


Biospecimen Retention:   Samples With DNA
Blood lymphocytes from enrolled subjects will be retained until all investigations will be performed and publications are generated. After that remaining samples will be discarded properly according to the Biosafety instructions.

Enrollment: 10
Study Start Date: January 2012
Study Completion Date: December 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
10 Hepatitis C infected subjects
10 chronically HCV-infected patients who fail the standard peg-IFN and Ribavirin therapy (NR) and are therefore eligible for combined treatment with Protease Inhibitor therapy.

Detailed Description:

Objective 1: Evaluate the role of the immune responses in determining the emergence of HCV NS3 resistance mutation during protease inhibitor therapy

Hypothesis 1 (HT 1): Low HLA binding to peptides containing protease inhibitor resistance mutations is associated with the emergence of protease inhibitor mutants during therapy and failure of the treatment.

Hypothesis 2 (HT 2): A hole in T cell repertoire may allow emergence of protease inhibitor mutants during protease inhibitor therapy which leads to loss of the immune responses to these mutants and failure of treatment.

  Eligibility
Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Investigators plan to enroll 20 human subjects with chronic hepatitis C virus infection from the outpatient clinic at the University of Cincinnati College of Medicine.
Criteria

Inclusion Criteria: All chronically HCV-infected patients who fail peg-IFN and RBV therapy and are eligible for combined treatment with PI therapy will be enrolled. Briefly, this includes:

  1. Male or female
  2. Age 18 to 65
  3. Chronic HCV infection evidenced by liver biopsy or persistent HCV viremia for >6 months
  4. Treatment experienced and classified as non-responder or relapser to prior interferon-based therapy.

Exclusion criteria:

  1. Treatment naïve chronically HCV-infected patients.
  2. Patients with a history of inflammatory bowel diseases (IBD) or suspected IBD, autoimmune diseases, including rheumatoid arthritis, and any patients on systemic immunomodulators.
  3. Pregnancy
  4. HIV
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01517529

Locations
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267
Sponsors and Collaborators
University of Cincinnati
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Mohamed Tarek. M Shata, MD, PhD University of Cincinnati
  More Information

Responsible Party: Mohamed Tarek Shata, Principal investigator, University of Cincinnati
ClinicalTrials.gov Identifier: NCT01517529     History of Changes
Other Study ID Numbers: UC 11101915 
Study First Received: January 20, 2012
Results First Received: August 25, 2015
Last Updated: October 20, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by University of Cincinnati:
Hepatitis C
HCV

Additional relevant MeSH terms:
Hepatitis
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
 Protease Inhibitors
HIV Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 30, 2016