Hepatitis C InfectionPhase 4NCT02429583
Effects of Persistent Innate Immune Activation on Vaccine Efficacy
A Phase 4 study testing Recombivax in people with Hepatitis C Infection, run by Rockefeller University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 62 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis C Infection
- What is being tested?
- Recombivax
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 8 May 2015to Nov 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 62 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Rockefeller University Hospital
New York, New York, 10065
About this study
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.
Read the 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.
- Conditions
- Hepatitis C Infection
- Being tested
- Recombivax
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RecombivaxDrug
Also called Hepatitis B vaccine
Injection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment
| Study group | Role | What they receive |
|---|---|---|
| Recombivax in HCV infected individuals | Active comparator | Recombivax vaccine administered IM to HCV-infected individuals Receives: Drug: Recombivax |
| Recombivax in healthy volunteers | Active comparator | Recombivax vaccine administered IM to healthy individuals Receives: Drug: Recombivax |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 8 months
Secondary outcomes (4)
Frequency and Functional Status of Anti-HBsAg Antibody-producing B Cells Post-vaccination Doses Over Time
ELISPOT assays will measured at 8 months
Measured: 8 months
Frequency and Functional Status of HBsAg-specific CD4+ "Helper" T Cells
Flow cytometry assays measured at 8 months
Measured: 8 months
Functional Response of Monocytes Stimulated ex Vivo With Vaccine Antigen and/or Adjuvant
Isolated from patient PBMCs measured at 8 months
Measured: 8 months
Gene Expression Profile of Conventional Dendritic Cells Measured by RNA-Seq
Isolated from patient PBMCs measured at 8 months
Measured: 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2015 (estimated)
- Study start8 May 2015
- Primary completionNov 2018
- Study completionNov 2018
Why it stopped: Unable to enroll sufficient subjects
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatitis C InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rockefeller University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Charles Rice, Rockefeller University
- Investigators
- Charles Rice, PhD, Principal investigator, The Rockefeller University Center for Clinical and Translational
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02429583
- Sponsor's protocol ID
- CRI-0844
- Other IDs
- U19AI111825
- Status last verified
- Feb 2020
- First submitted
- 24 Apr 2015
- Last updated
- 4 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Persistent Innate Immune Activation on Vaccine Efficacy
- ClinicalTrials.gov ID
- NCT02429583
- Acronym / sponsor ID
- CRI-0844
- Conditions
- Hepatitis C Infection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unable to enroll sufficient subjects
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Rockefeller UniversityUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 8 May 2015 (actual)
- Primary completion
- Nov 2018 (actual)
- Study completion
- Nov 2018 (actual)
- First posted
- 29 Apr 2015 (estimated)
- Results
- Posted 4 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Recombivax in HCV infected individuals | Active comparator | Drug: RecombivaxRecombivax vaccine administered IM to HCV-infected individuals |
| Recombivax in healthy volunteers | Active comparator | Drug: RecombivaxRecombivax vaccine administered IM to healthy individuals |
Who may qualify
- Ages
- 18 to 62 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RecombivaxAlso: Hepatitis B vaccineInjection of Recombivax HBV vaccine administered IM, at 0, 1, and 6 months after enrollment | Drug | Recombivax in HCV infected individuals, Recombivax in healthy volunteers |
Primary outcome
HBV Vaccine Response Versus Non-response Status
Time frame: 8 months
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
4 secondary outcomes
Frequency and Functional Status of Anti-HBsAg Antibody-producing B Cells Post-vaccination Doses Over Time
Time frame: 8 months
Frequency and Functional Status of HBsAg-specific CD4+ "Helper" T Cells
Time frame: 8 months
Functional Response of Monocytes Stimulated ex Vivo With Vaccine Antigen and/or Adjuvant
Time frame: 8 months
Gene Expression Profile of Conventional Dendritic Cells Measured by RNA-Seq
Time frame: 8 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles Rice, PhD principal investigator
The Rockefeller University Center for Clinical and Translational
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Recombivax in people with Hepatitis C Infection, run by Rockefeller University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HBV Vaccine Response Versus Non-response Status (time frame: 8 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2020.