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Effects of Persistent Innate Immune Activation on Vaccine Efficacy

Primary Purpose

Hepatitis C Infection

Status

Terminated

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Recombivax

About this trial

This is an interventional basic science trial for Hepatitis C Infection

Eligibility Criteria

18 Years - 62 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Willing to receive three doses of an FDA-approved Hepatitis B vaccine
Volunteer chronically infected with HCV (as demonstrated by serology and/or viral load laboratory studies)
Healthy volunteer without significant medical problems

Exclusion Criteria:

Received any vaccine within a month prior to study vaccine
Positive serum antibody against Hep B surface antigen and/or core Hep B core antigen
HIV positive
For HCV-negative, healthy volunteers: History of HCV infection or positive HCV antibody test
Participation in another clinical study of an investigational product currently or within the past 90 days, or expected participation during this study
In the opinion of the investigator, the volunteer is unlikely to comply with the study protocol
Any clinically significant abnormality or medical history or physical examination including history of immunodeficiency or autoimmune disease (in addition to HCV infection, for HCV group)
Currently taking systemic steroids or other immunomodulatory medications including anticancer medications and antiviral medications
Any clinically significant acute or chronic medical condition requiring care by a primary care provider (e.g., diabetes, coronary artery disease, rheumatologic illness, malignancy, substance abuse) that, in the opinion of the investigator, would preclude participation
Unable to continue participation for 156 weeks
History of previous Hepatitis B vaccination(s)
Male or female < 18 and > 62 years of age
Is pregnant or lactating
History of Hepatitis B infection
Clinical, laboratory, or biopsy evidence of cirrhosis

Sites / Locations

Rockefeller University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Recombivax in HCV infected individuals

Recombivax in healthy volunteers

Arm Description

Recombivax vaccine administered IM to HCV-infected individuals

Recombivax vaccine administered IM to healthy individuals

Outcomes

Primary Outcome Measures

HBV Vaccine Response Versus Non-response Status

Titers of anti-hepatitis B surface antigen antibody measured at 8 months Luminex assay for multiplex cytokine/chemokine panel measured at 8 months RNA-Seq with analysis focus on curated ISG list measured at 8 months

Secondary Outcome Measures

Frequency and Functional Status of Anti-HBsAg Antibody-producing B Cells Post-vaccination Doses Over Time

ELISPOT assays will measured at 8 months

Frequency and Functional Status of HBsAg-specific CD4+ "Helper" T Cells

Flow cytometry assays measured at 8 months

Functional Response of Monocytes Stimulated ex Vivo With Vaccine Antigen and/or Adjuvant

Isolated from patient PBMCs measured at 8 months

Gene Expression Profile of Conventional Dendritic Cells Measured by RNA-Seq

Isolated from patient PBMCs measured at 8 months

Full Information

NCT ID

NCT02429583

First Posted

April 24, 2015

Last Updated

February 20, 2020

Sponsor

Rockefeller University

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

1. Study Identification

Unique Protocol Identification Number

NCT02429583

Brief Title

Effects of Persistent Innate Immune Activation on Vaccine Efficacy

Official Title

Effects of Persistent Innate Immune Activation on Vaccine Efficacy

Study Type

Interventional

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Terminated

Why Stopped

Unable to enroll sufficient subjects

Study Start Date

May 8, 2015 (Actual)

Primary Completion Date

November 2018 (Actual)

Study Completion Date

November 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Rockefeller University

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This study will investigate the effects of chronic HCV infection and corresponding innate immune activation on the immune response to HBV vaccination. We will recruit chronic HCV patients and healthy control patients for HBV vaccination. We will use RNA Sequencing (RNA-Seq), a relatively new technology for simultaneously measuring the expression of all genes, to determine patients' innate immune status, and learn how this innate immune signature is related to HBV vaccine response. We will then explore the mechanisms by which chronic HCV infection affects different immune cells and functions that are known to be important for an effective HBV vaccine response. These studies will enhance our understanding of the immune effects of chronic viral infection, establish factors that determine effective vaccine responses, and help guide vaccination strategies for HCV patients and other individuals with chronic inflammatory disease.

Detailed Description

Vaccines have been responsible for preventing millions of deaths and extending the average human lifespan. Effective vaccines stimulate the cells of the immune system to activate genes and associated functions that bring about protective immunity. If we can better understand the factors that influence vaccine success versus failure, we may be able to improve current vaccines and/or develop new vaccines against prevalent infectious diseases. Certain groups of people do not respond well to particular vaccines. For example, vaccines can be less effective in immunocompromised patients, elderly individuals, and people with chronic inflammatory diseases. Often it is these groups of people that have the greatest need for protection against infectious disease. People chronically infected with hepatitis C virus (HCV) are at increased risk of serious liver disease. As a result, they should receive the hepatitis B virus (HBV) vaccine, which can protect them from infection by HBV, another virus that targets the liver. However, people chronically infected with HCV do not respond to the HBV vaccine as effectively as healthy people without HCV. Chronic HCV infection is not thought to cause general problems with the immune system, and the reasons for this poor vaccine response are poorly understood. Previous work has shown that chronic HCV infection leads to production of chemical ("innate immune") signals that can affect function of the immune system, but it is currently unknown how this might impact vaccination.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis C Infection

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Recombivax in HCV infected individuals

Arm Type

Active Comparator

Arm Description

Recombivax vaccine administered IM to HCV-infected individuals

Arm Title

Recombivax in healthy volunteers

Arm Type

Active Comparator

Arm Description

Recombivax vaccine administered IM to healthy individuals

Intervention Type

Drug

Intervention Name(s)

Recombivax

Other Intervention Name(s)

Hepatitis B vaccine

Intervention Description

Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment

Primary Outcome Measure Information:

Title

HBV Vaccine Response Versus Non-response Status

Description

Time Frame

8 months

Secondary Outcome Measure Information:

Title

Frequency and Functional Status of Anti-HBsAg Antibody-producing B Cells Post-vaccination Doses Over Time

Description

ELISPOT assays will measured at 8 months

Time Frame

8 months

Title

Frequency and Functional Status of HBsAg-specific CD4+ "Helper" T Cells

Description

Flow cytometry assays measured at 8 months

Time Frame

8 months

Title

Functional Response of Monocytes Stimulated ex Vivo With Vaccine Antigen and/or Adjuvant

Description

Isolated from patient PBMCs measured at 8 months

Time Frame

8 months

Title

Gene Expression Profile of Conventional Dendritic Cells Measured by RNA-Seq

Description

Isolated from patient PBMCs measured at 8 months

Time Frame

8 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

62 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Willing to receive three doses of an FDA-approved Hepatitis B vaccine Volunteer chronically infected with HCV (as demonstrated by serology and/or viral load laboratory studies) Healthy volunteer without significant medical problems Exclusion Criteria: Received any vaccine within a month prior to study vaccine Positive serum antibody against Hep B surface antigen and/or core Hep B core antigen HIV positive For HCV-negative, healthy volunteers: History of HCV infection or positive HCV antibody test Participation in another clinical study of an investigational product currently or within the past 90 days, or expected participation during this study In the opinion of the investigator, the volunteer is unlikely to comply with the study protocol Any clinically significant abnormality or medical history or physical examination including history of immunodeficiency or autoimmune disease (in addition to HCV infection, for HCV group) Currently taking systemic steroids or other immunomodulatory medications including anticancer medications and antiviral medications Any clinically significant acute or chronic medical condition requiring care by a primary care provider (e.g., diabetes, coronary artery disease, rheumatologic illness, malignancy, substance abuse) that, in the opinion of the investigator, would preclude participation Unable to continue participation for 156 weeks History of previous Hepatitis B vaccination(s) Male or female < 18 and > 62 years of age Is pregnant or lactating History of Hepatitis B infection Clinical, laboratory, or biopsy evidence of cirrhosis

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Charles Rice, PhD

Organizational Affiliation

The Rockefeller University Center for Clinical and Translational

Official's Role

Principal Investigator

Facility Information:

Facility Name

Rockefeller University Hospital

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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Effects of Persistent Innate Immune Activation on Vaccine Efficacy

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