NCT03119025

Brief 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). 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started May 2015

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2015

Completed
1.9 years until next milestone

First Submitted

Initial submission to the registry

March 27, 2017

Completed
22 days until next milestone

First Posted

Study publicly available on registry

April 18, 2017

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2018

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2018

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

May 10, 2019

Completed
Last Updated

May 10, 2019

Status Verified

February 1, 2019

Enrollment Period

2.8 years

First QC Date

March 27, 2017

Results QC Date

April 15, 2018

Last Update Submit

February 6, 2019

Conditions

Hepatitis C, ChronicLiver DiseasesHepatitisVirus Diseases

Keywords

Dendritic CellsDC-based VaccinesChronic HCV InfectionAntigen-Specific T cell responseRecombinant HCV-Core antigenRecombinant HCV-NS3 antigen

Outcome Measures

Primary Outcomes (1)

  • 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).

    From enrollment and up to 13 months

Secondary Outcomes (3)

  • Number of Participants With Virological Response According to HCV RNA Viral Load

    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

    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

    Baseline, 2, 7 and 13 months after 1-st vaccination

Study Arms (1)

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.

Biological: Autologous DC-vaccines

Interventions

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).

Autologous DC-vaccines

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • Renal dysfunctions
  • Hemodynamic or respiratory instability
  • HIV or uncontrolled bacterial, fungal, or viral infections
  • Autoimmune diseases
  • Pregnancy
  • Malignancy
  • Participation in other clinical trials

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Institute of Fundamental and Clinical Immunology

Novosibirsk, 630099, Russia

Location

Related Publications (1)

  • 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

    BACKGROUND

MeSH Terms

Conditions

Hepatitis C, ChronicLiver DiseasesHepatitisVirus Diseases

Condition Hierarchy (Ancestors)

Hepatitis CBlood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanFlaviviridae InfectionsRNA Virus InfectionsHepatitis, ChronicDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Results Point of Contact

Title
Alexander A Ostanin, MD, PhD Study Principal Investigator
Organization
Institute of Fundamental and Clinical Immunology
ct_lab@mail.ru; ostanin62@mail.ru
383-236-03-29

Study Officials

  • Elena R Chernykh, MD, PhD

    Institute of Fundamental and Clinical Immunology

    STUDY CHAIR

  • Alexander A Ostanin, MD, PhD

    Institute of Fundamental and Clinical Immunology

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Head of Clinical Department

Study Record Dates

First Submitted

March 27, 2017

First Posted

April 18, 2017

Study Start

May 1, 2015

Primary Completion

February 1, 2018

Study Completion

April 1, 2018

Last Updated

May 10, 2019

Results First Posted

May 10, 2019

Record last verified: 2019-02

Locations

RU(1)