Effects of Persistent Innate Immune Activation on Vaccine Efficacy

NCT02429583 | Terminated Phase 4 Results

• 2 other identifiers: CRI-0844U19AI111825
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis C Infection

Outcome Measures

Primary Outcomes (1)

• 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

  8 months

Secondary Outcomes (4)

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

  8 months

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

  8 months

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

  8 months

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

  8 months

Study Arms (2)

Recombivax in HCV infected individuals

ACTIVE COMPARATOR

Recombivax vaccine administered IM to HCV-infected individuals

Drug: Recombivax

Recombivax in healthy volunteers

ACTIVE COMPARATOR

Recombivax vaccine administered IM to healthy individuals

Drug: Recombivax

Interventions

Recombivax DRUG

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

Also known as: Hepatitis B vaccine

Recombivax in HCV infected individuals; Recombivax in healthy volunteers

Eligibility Criteria

• Age: 18 Years - 62 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rockefeller University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Rockefeller University Hospital

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Hepatitis C

Interventions

Recombivax HB; Hepatitis B Vaccines

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Viral Hepatitis Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Aileen O'Connell, Laboratory Manager
• Organization: The Rockefeller University

aoconnell@rockefeller.edu

212-327-7047

Study Officials

• Charles Rice, PhD

  The Rockefeller University Center for Clinical and Translational

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Laboratory of Virology and Infectious Disease

Study Record Dates

• First Submitted: April 24, 2015
• First Posted: April 29, 2015
• Study Start: May 8, 2015
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2018
• Last Updated: March 4, 2020
• Results First Posted: March 4, 2020

Record last verified: 2020-02

Locations

US (1)