Hepatitis C, ChronicPhase 1/2NCT03119025
Autologous Dendritic Cell Vaccine for Treatment of Patients With Chronic HCV-Infection
A Phase 1/2 study testing Autologous DC-vaccines in people with Hepatitis C, Chronic and Liver Diseases, run by Russian Academy of Medical Sciences at 1 site in Russia.
Trial summary
Clearance of HCV infection requires early and multi-specific HLA class I restricted CD8+ T cell and class II restricted CD4+ T cell responses to both structural (Core) and non-structural HCV proteins (NS3, NS4A, NS5A, NS5B). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hepatitis C, Chronic, Liver Diseases, Hepatitis
- What is being tested?
- Autologous DC-vaccines
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteRussia
- Study dates
- May 2015to Apr 2018
- Phase
- Phase 1/2
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 to 65 Years (Adult)
- Chronic hepatitis C (genotype 1b)
- HCV-positive patients
- Plasma HCV RNA level ≥ 10 000 IU/ml
- Liver fibrosis (METAVIR Score 0-III)
- Patients must be able to tolerate all study procedures
- Patients must be willing to voluntarily give written Informed Consent to participate in the study before any procedures are performed
- Patients must be willing to be available for all baseline, treatment and follow-up examinations required by protocol
Who cannot join
- Co-infection with hepatitis B, A, D, E, cytomegalovirus or Epstein-Barr virus
- Liver cirrhosis (METAVIR Score IV)
- The high degree of hepatitis activity (ALT and/or AST ≥ 10 ULN)
- Received any vaccine within a month prior to study entry
- A history of diabetes
- Psychiatric disorders
Show all 13Show fewer
- Renal dysfunctions
- Hemodynamic or respiratory instability
- HIV or uncontrolled bacterial, fungal, or viral infections
- Autoimmune diseases
- Pregnancy
- Malignancy
- Participation in other clinical trials
Trial locations and contacts
1 site in 1 country.
Russia1 site
Institute of Fundamental and Clinical Immunology
Novosibirsk, 630099
About this study
Official title: Safety/Efficacy of Vaccination With Autologous Dendritic Cells Pulsed With Recombinant HCV-Antigens (Core and NS3) for Treatment of Patients With Chronic HCV-Infection
Clearance of HCV infection requires early and multi-specific HLA class I restricted CD8+ T cell and class II restricted CD4+ T cell responses to both structural (Core) and non-structural HCV proteins (NS3, NS4A, NS5A, NS5B). Dendritic cells (DCs) are professional antigen-presenting cells that link innate and adaptive immune responses, and play a major role in priming, initiating, and sustaining strong anti-HCV T cell immune responses.
The general objective of this study is to evaluate safety, feasibility and clinical efficacy of therapeutic vaccination in genotype 1 HCV patients using autologous DCs pulsed with recombinant HCV-antigens (Core and NS3). Expected effects: DC vaccination induces Core/NS3-specific immune response and reduces viral load in patients with chronic HCV-infection.
Read the detailed description
Hepatitis C virus (HCV) has chronically infected an estimated 170 million people worldwide. People infected with HCV are at risk for developing chronic liver diseases, such as liver cirrhosis and primary hepatocellular carcinoma. It has been estimated that HCV accounts for 27% of cirrhosis and 25% of hepatocellular carcinoma worldwide. Therapy for chronically HCV-infected patients has involved a pegylated interferon-alpha and ribavirin (pegIFN/RBV) and is still the only FDA-approved therapeutic combination. However, this therapy is expensive, non-specific, toxic, and only effective in about 50% of genotype-1 HCV patients.
An early immune response, represented by the activation of NK cells, the development of vigorous anti-HCV CD4+ and CD8+ T-cell responses, and the appearance of HCV-specific antibodies, is mounted by the host during acute HCV infection and leads to clearance of the virus. However, in the vast majority (≈85%) of infected individuals HCV causes a persistent infection. The mechanisms of HCV persistence remain elusive and are largely related to inefficient clearance of the virus by the host immune system.
Although HCV genome is very variable with hundreds of serotypes and six genotypes, several structural (Core) and nonstructural proteins (NS3, NS4A, NS5A, NS5B) are highly conserved among genotypes and subtypes. It is apparent that clearance of hepatitis C infection requires early and multi-specific HLA class I restricted CD8+ T cell and class II restricted CD4+ T cell responses to both structural and non-structural HCV proteins.
DCs are professional antigen-presenting cells that link innate and adaptive immune responses. DCs play a major role in priming, initiating, and sustaining strong T cell responses against pathogen-derived antigens. Therefore DC-based therapy represents a promising immunotherapeutic approach in terms of their propensity to establish anti-HCV adaptive immune responses.
This trial is a prospective, non-blinded, interventional study to determine safety, feasibility and clinical efficacy of therapeutic vaccination in genotype 1 HCV patients using autologous DCs pulsed with recombinant HCV-antigens (Core and NS3). Our previous work has shown that the short-term loading of DCs with recombinant HCV proteins Core (1-120) and NS3 (1192-1457) have no any marked inhibitory effect on maturation and functions of DCs.
In experimental group thirty patients with chronic hepatitis C (genotype 1) will be vaccinated via intracutaneous injection of monocyte-derived DCs, generated in the presence of IFN-α/GM-CSF and pulsed with recombinant HCV Core (1-120) and NS3 (1192-1457) proteins. The vaccination protocol will includes initiating (one injection per week, no 4) and maintaining (one injection per month, no 6) courses with subsequent 6-month of follow up.
The safety will be determined by the evaluation of the number of participants with the adverse events. Liver safety will be assessed by blood analysis and Ultrasound. Patients will be monitored in a 2 months (after completing of initiating course), 7 months (after completing of maintaining course) and 13 months (in a 6 months post-vaccination follow-up).
- Conditions
- Hepatitis C, Chronic, Liver Diseases, Hepatitis, Virus Diseases
- Being tested
- Autologous DC-vaccines
- Keywords
- Dendritic Cells, DC-based Vaccines, Chronic HCV Infection, Antigen-Specific T cell response, Recombinant HCV-Core antigen, Recombinant HCV-NS3 antigen
- Medical subject headings
- Hepatitis C, Chronic, Liver Diseases, Hepatitis, Virus Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous DC-vaccinesBiological
Patients will be vaccinated via intracutaneous injection of autologous DCs (5×106) combined with adjuvant subcutaneous injection of recombinant hIL-2 (250 000 IU).
Initiating course: one vaccination per week, during 1 month. Maintaining course: one vaccination per month, during 6 month. Patients will be monitored in a 2 months (after completing of initiating course), 7 months (after completing of maintaining course) and 13 months (in a 6 months post-vaccination follow-up).
| Study group | Role | What they receive |
|---|---|---|
| Autologous DC-vaccines | Experimental | Thirty patients with chronic hepatitis C (genotype 1) will receive the initiating and maintaining courses of autologous of autologous monocyte-derived dendritic cells, generated in the presence of IFN-α/GM-CSF and pulsed with recombinant HCV Core (1-120) and NS3 (1192-1457) proteins. Receives: Biological: Autologous DC-vaccines |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Severe Adverse Reactions and/or With Abnormal Clinical Laboratory Values That Are Related to Treatment
Frequency of severe adverse reactions will be evaluated from enrollment and up to 13 months. Liver safety by blood analysis (ALT, AST, GGT, Total and conjugated bilirubin, platelets, ESR, etc) and Ultrasound will be assessed from enrollment and up to 13 months (= baseline, 2, 7 and 13 months after 1-st vaccination).
Measured: From enrollment and up to 13 months
Secondary outcomes (3)
Number of Participants With Virological Response According to HCV RNA Viral Load
Virological response in patients receiving DC-vaccinations is defined as change from baseline in HCV RNA viral load by at least 1 log at 2, 7 and 13 month after 1-st vaccination. Plasma level of HCV RNA will be measured by Real-Time Reverse Transcription-Polymerase Chain Reaction (RT-PCR)
Measured: Baseline, 2, 7 and 13 months after 1-st vaccination
Number of Participants Who Have Developed or Increased Anti-Viral Immune Response According to T-cell Proliferation
Change from baseline in T-cell proliferative response to HCV Core and NS3 proteins at 2, 7 and 13 month after 1-st vaccination. T-cell proliferation will be evaluated using radiometry based on 3H-thymidine incorporation
Measured: Baseline, 2, 7, and 13 months after 1-st vaccination
Number of Participants Who Have Developed or Increased Anti-Viral Immune Response According to IFN-γ Production
Change from baseline in T-cell IFN-γ-producing response to HCV Core and NS3 proteins at 2, 7 and 13 month after 1-st vaccination. Production of IFN-γ will be measured by ELISA kit
Measured: Baseline, 2, 7 and 13 months after 1-st vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2017
- Study startMay 2015
- Primary completionFeb 2018
- Study completionApr 2018
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis C, ChronicStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Russian Academy of Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alexander A Ostanin, Russian Academy of Medical Sciences
- Investigators
- Elena R Chernykh, MD, PhD, Study chair, Institute of Fundamental and Clinical ImmunologyAlexander A Ostanin, MD, PhD, Principal investigator, Institute of Fundamental and Clinical Immunology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03119025
- Sponsor's protocol ID
- IFCI-04/10/2015
- Status last verified
- Feb 2019
- First submitted
- 27 Mar 2017
- Last updated
- 10 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Oleynik EA, Leplina OY, Tyrinova TV, Tikhonova MA, Pyrinova GB, Ostanin AA, Starostina NM, Chernykh ER. The influence of recombinant HCV proteins Core and NS3 on maturation and functions of dendritic cells generated in vitro with interferon-alpha. Immunology 37 (5): 239-245, 2016. (in Russian) DOI: 10.18821/0206-4952-2016-37-5-239-245
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety/Efficacy of Vaccination With Autologous Dendritic Cells Pulsed With Recombinant HCV-Antigens (Core and NS3) for Treatment of Patients With Chronic HCV-Infection
- ClinicalTrials.gov ID
- NCT03119025
- Acronym / sponsor ID
- IFCI-04/10/2015
- Conditions
- Hepatitis C, Chronic, Liver Diseases, Hepatitis, Virus Diseases
- Keywords
- Dendritic Cells, DC-based Vaccines, Chronic HCV Infection, Antigen-Specific T cell response, Recombinant HCV-Core antigen, Recombinant HCV-NS3 antigen
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Russian Academy of Medical SciencesUniversity, hospital or other
- Study start
- May 2015 (actual)
- Primary completion
- Feb 2018 (actual)
- Study completion
- Apr 2018 (actual)
- First posted
- 18 Apr 2017 (actual)
- Results
- Posted 10 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Clearance of HCV infection requires early and multi-specific HLA class I restricted CD8+ T cell and class II restricted CD4+ T cell responses to both structural (Core) and non-structural HCV proteins (NS3, NS4A, NS5A, NS5B). Dendritic cells (DCs) are professional antigen-presenting cells that link innate and adaptive immune responses, and play a major role in priming, initiating, and sustaining strong anti-HCV T cell immune responses.
The general objective of this study is to evaluate safety, feasibility and clinical efficacy of therapeutic vaccination in genotype 1 HCV patients using autologous DCs pulsed with recombinant HCV-antigens (Core and NS3). Expected effects: DC vaccination induces Core/NS3-specific immune response and reduces viral load in patients with chronic HCV-infection.
Detailed description
Hepatitis C virus (HCV) has chronically infected an estimated 170 million people worldwide. People infected with HCV are at risk for developing chronic liver diseases, such as liver cirrhosis and primary hepatocellular carcinoma. It has been estimated that HCV accounts for 27% of cirrhosis and 25% of hepatocellular carcinoma worldwide. Therapy for chronically HCV-infected patients has involved a pegylated interferon-alpha and ribavirin (pegIFN/RBV) and is still the only FDA-approved therapeutic combination. However, this therapy is expensive, non-specific, toxic, and only effective in about 50% of genotype-1 HCV patients.
An early immune response, represented by the activation of NK cells, the development of vigorous anti-HCV CD4+ and CD8+ T-cell responses, and the appearance of HCV-specific antibodies, is mounted by the host during acute HCV infection and leads to clearance of the virus. However, in the vast majority (≈85%) of infected individuals HCV causes a persistent infection. The mechanisms of HCV persistence remain elusive and are largely related to inefficient clearance of the virus by the host immune system.
Although HCV genome is very variable with hundreds of serotypes and six genotypes, several structural (Core) and nonstructural proteins (NS3, NS4A, NS5A, NS5B) are highly conserved among genotypes and subtypes. It is apparent that clearance of hepatitis C infection requires early and multi-specific HLA class I restricted CD8+ T cell and class II restricted CD4+ T cell responses to both structural and non-structural HCV proteins.
DCs are professional antigen-presenting cells that link innate and adaptive immune responses. DCs play a major role in priming, initiating, and sustaining strong T cell responses against pathogen-derived antigens. Therefore DC-based therapy represents a promising immunotherapeutic approach in terms of their propensity to establish anti-HCV adaptive immune responses.
This trial is a prospective, non-blinded, interventional study to determine safety, feasibility and clinical efficacy of therapeutic vaccination in genotype 1 HCV patients using autologous DCs pulsed with recombinant HCV-antigens (Core and NS3). Our previous work has shown that the short-term loading of DCs with recombinant HCV proteins Core (1-120) and NS3 (1192-1457) have no any marked inhibitory effect on maturation and functions of DCs.
In experimental group thirty patients with chronic hepatitis C (genotype 1) will be vaccinated via intracutaneous injection of monocyte-derived DCs, generated in the presence of IFN-α/GM-CSF and pulsed with recombinant HCV Core (1-120) and NS3 (1192-1457) proteins. The vaccination protocol will includes initiating (one injection per week, no 4) and maintaining (one injection per month, no 6) courses with subsequent 6-month of follow up.
The safety will be determined by the evaluation of the number of participants with the adverse events. Liver safety will be assessed by blood analysis and Ultrasound. Patients will be monitored in a 2 months (after completing of initiating course), 7 months (after completing of maintaining course) and 13 months (in a 6 months post-vaccination follow-up).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Autologous DC-vaccines | Experimental | Biological: Autologous DC-vaccinesThirty patients with chronic hepatitis C (genotype 1) will receive the initiating and maintaining courses of autologous of autologous monocyte-derived dendritic cells, generated in the presence of IFN-α/GM-CSF and pulsed with recombinant HCV Core (1-120) and NS3 (1192-1457) proteins. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18 to 65 Years (Adult)
- Chronic hepatitis C (genotype 1b)
- HCV-positive patients
- Plasma HCV RNA level ≥ 10 000 IU/ml
- Liver fibrosis (METAVIR Score 0-III)
Key exclusion criteria (13 listed)
- Co-infection with hepatitis B, A, D, E, cytomegalovirus or Epstein-Barr virus
- Liver cirrhosis (METAVIR Score IV)
- The high degree of hepatitis activity (ALT and/or AST ≥ 10 ULN)
- Received any vaccine within a month prior to study entry
- A history of diabetes
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 |
|---|---|---|
| Autologous DC-vaccinesPatients will be vaccinated via intracutaneous injection of autologous DCs (5×106) combined with adjuvant subcutaneous injection of recombinant hIL-2 (250 000 IU). Initiating course: one vaccination per week, during 1 month. Maintaining course: one vaccination per month, during 6 month. Patients will be monitored in a 2 months (after completing of initiating course), 7 months (after completing of maintaining course) and 13 months (in a 6 months post-vaccination follow-up). | Biological | Autologous DC-vaccines |
Primary outcome
Number of Participants With Severe Adverse Reactions and/or With Abnormal Clinical Laboratory Values That Are Related to Treatment
Time frame: From enrollment and up to 13 months
Frequency of severe adverse reactions will be evaluated from enrollment and up to 13 months. Liver safety by blood analysis (ALT, AST, GGT, Total and conjugated bilirubin, platelets, ESR, etc) and Ultrasound will be assessed from enrollment and up to 13 months (= baseline, 2, 7 and 13 months after 1-st vaccination).
3 secondary outcomes
Number of Participants With Virological Response According to HCV RNA Viral Load
Time frame: Baseline, 2, 7 and 13 months after 1-st vaccination
Number of Participants Who Have Developed or Increased Anti-Viral Immune Response According to T-cell Proliferation
Time frame: Baseline, 2, 7, and 13 months after 1-st vaccination
Number of Participants Who Have Developed or Increased Anti-Viral Immune Response According to IFN-γ Production
Time frame: Baseline, 2, 7 and 13 months after 1-st vaccination
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundOleynik EA, Leplina OY, Tyrinova TV, Tikhonova MA, Pyrinova GB, Ostanin AA, Starostina NM, Chernykh ER. The influence of recombinant HCV proteins Core and NS3 on maturation and functions of dendritic cells generated in vitro with interferon-alpha. Immunology 37 (5): 239-245, 2016. (in Russian) DOI: 10.18821/0206-4952-2016-37-5-239-245
- 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.
Elena R Chernykh, MD, PhD study chair
Institute of Fundamental and Clinical Immunology
Alexander A Ostanin, MD, PhD principal investigator
Institute of Fundamental and Clinical Immunology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Autologous DC-vaccines in people with Hepatitis C, Chronic and Liver Diseases, run by Russian Academy of Medical Sciences at 1 site in Russia.
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 8 inclusion and 13 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: finished, as of the sponsor's last update on 10 May 2019. 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 Russia. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 10 May 2019). 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?
Number of Participants With Severe Adverse Reactions and/or With Abnormal Clinical Laboratory Values That Are Related to Treatment (time frame: From enrollment and up to 13 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03119025, which also lists 1 linked publication.
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 10 May 2019.