ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 63 of 325 for:    hepatitis b | Recruiting, Not yet recruiting, Available Studies

A First-In-Human Study to Evaluate Safety, Tolerability, Reactogenicity, and Immunogenicity of JNJ-64300535, a DNA Vaccine, Administered by Electroporation-Mediated Intramuscular Injection, in Participants With Chronic Hepatitis B Who Are on Stable Nucleos(t)Ide Therapy and Virologically Suppressed

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03463369
Recruitment Status : Not yet recruiting
First Posted : March 13, 2018
Last Update Posted : March 29, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen Sciences Ireland UC

Brief Summary:
The purpose of this study is to evaluate the safety, tolerability and reactogenicity of escalating doses of JNJ-64300535 delivered via electroporation-mediated intramuscular injection in nucleos(t)ide analogs (NA)-treated chronic hepatitis B (CHB) participants.

Condition or disease Intervention/treatment Phase
Hepatitis B, Chronic Biological: JNJ-64300535 Biological: Placebo Drug: Nucleos(t)ide Analogs (NA) Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: A First-In-Human, Double-Blind, Randomized, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability, Reactogenicity, and Immunogenicity of JNJ-64300535, a DNA Vaccine, Administered by Electroporation-Mediated Intramuscular Injection, in Participants With Chronic Hepatitis B Who Are on Stable Nucleos(t)Ide Therapy and Virologically Suppressed
Estimated Study Start Date : March 29, 2018
Estimated Primary Completion Date : November 12, 2019
Estimated Study Completion Date : November 12, 2019

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Placebo + Nucleos(t)ide Analogs (NA)
Participants will receive placebo intramuscular (IM) injection on Day 1, Week 4, and Week 12, along with standard of care NA treatment.
Biological: Placebo
Participants will receive 1 mL (0.9 percent [%] sodium chloride [NaCl]) of placebo solution matching to JNJ-64300535 electroporation-mediated IM injection on Day 1, Week 4, and Week 12.
Drug: Nucleos(t)ide Analogs (NA)
Participants will receive NA as a standard of care treatment.
Experimental: JNJ-64300535 + NA
Participants will receive JNJ-64300535 IM injection on Day 1, Week 4, and Week 12, along with standard of care NA treatment.
Biological: JNJ-64300535
Participants will receive JNJ-64300535 vaccine by electroporation-mediated IM injection on Day 1, Week 4, and Week 12.
Drug: Nucleos(t)ide Analogs (NA)
Participants will receive NA as a standard of care treatment.



Primary Outcome Measures :
  1. Number of Participants with Adverse Events (AEs) by Severity and Relationship to Study Treatment and Dose Level [ Time Frame: Up to Week 16 ]
    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of AEs will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events as follows: Mild = Grade 1, Moderate = Grade 2, Severe = Grade 3, Potentially life-threatening = Grade 4.

  2. Number of Participants With Laboratory Abnormalities [ Time Frame: Up to Week 16 ]
    Number of participants with laboratory abnormalities related to hematology, serum chemistry, coagulation, liver function tests and urinalysis will be reported. Laboratory abnormalities will be graded according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events as follows: Mild = Grade 1, Moderate = Grade 2, Severe = Grade 3, Potentially life-threatening = Grade 4.

  3. Number of Participants With Clinically Significant Changes in Vital Signs [ Time Frame: Up to Week 16 ]
    Number of participants with clinically significant changes in the vital signs including blood pressure, pulse/heart rate, and body temperature will be reported.

  4. Number of Participants With Clinically Significant Changes in Physical Examination (Palpation of Lymph Nodes, Height, Body Weight, and Skin Examination) Findings [ Time Frame: Up to Week 16 ]
    Number of participants with clinically significant changes in physical examination parameters will be reported. Full physical examination (including palpation of lymph nodes, height, body weight, and skin examination) and symptom-directed physical examination will be performed.

  5. Number of Participants With Acute Injection Site Reactions on Day 1 [ Time Frame: From 0 to 2 hours post-vaccination on Day 1 ]
    Participants will be assessed for the acute injection site reactions. Acute reactions means the reactions which occur within 0 to 2 hours post-vaccination. Acute reactions will be graded as follows: Grade 0 = Normal, Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Potentially Life Threatening.

  6. Number of Participants With Acute Injection Site Reactions at Week 4 [ Time Frame: From 0 to 2 hours post-vaccination at Week 4 ]
    Participants will be assessed for the acute injection site reactions. Acute reactions means the reactions which occur within 0 to 2 hours post-vaccination. Acute reactions will be graded as follows: Grade 0 = Normal, Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Potentially Life Threatening.

  7. Number of Participants With Acute Injection Site Reactions at Week 12 [ Time Frame: From 0 to 2 hours post-vaccination at Week 12 ]
    Participants will be assessed for the acute injection site reactions. Acute reactions means the reactions which occur within 0 to 2 hours post-vaccination. Acute reactions will be graded as follows: Grade 0 = Normal, Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Potentially Life Threatening.

  8. Number of Participants With Injection Site Reactions After Vaccination on Day 1 [ Time Frame: Up to 7 days post-vaccination on Day 1 ]
    Participants will be assessed for the Reactogenicity. Reactogenicity means injection site reactions which occur after 7 days post- vaccination. Severity of reactions will be graded as follows: Grade 0 = Normal, Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Potentially Life Threatening.

  9. Number of Participants With Injection Site Reactions After Vaccination on Week 4 [ Time Frame: Up to 7 days post-vaccination on Week 4 ]
    Participants will be assessed for the Reactogenicity. Reactogenicity means injection site reactions which occur after 7 days post-vaccination. Severity of reactions will be graded as follows: Grade 0 = Normal, Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Potentially Life Threatening.

  10. Number of Participants With Injection Site Reactions After Vaccination on Week 12 [ Time Frame: Up to 7 days post-vaccination on Week 12 ]
    Participants will be assessed for the Reactogenicity. Reactogenicity means injection site reactions which occur after 7 days post- vaccination. Severity of reactions will be graded as follows: Grade 0 = Normal, Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Potentially Life Threatening.


Secondary Outcome Measures :
  1. Percentage of Participants With a Positive Hepatitis B Virus (HBV) Specific T Cells Response [ Time Frame: Day 1, Week 2, 6, 14, 24, 48, and 60 ]
    Percentage of participants with a positive HBV-specific T cells response, assessed by interferon (IFN)-gamma ELISpot assay will be reported.

  2. Time to Detection of HBV Specific T-Cell Responses [ Time Frame: Day 1 up to Week 60 ]
    Time to HBV Specific T-Cell response is defined as the time interval between Day 1 (vaccination) to the date of first evidence of positive HBV Specific T-Cell response.

  3. Percentage of CD4+ and CD8+ T-Cell Responses [ Time Frame: Day 1, Week 2, 6, 14, 24, 48, and 60 ]
    The activation of CD4+ and CD8+ T-cell subsets and their cytokine expression patterns (expressing at least 1 interleukin [IL]-2, tumor necrosis factor-alpha [TNF-α] or IFN-γ specific to any antigen) will be determined by Intracellular Cytokine Staining (ICS).

  4. Hepatitis B Antigen-Specific Cellular Immune Response [ Time Frame: Day 1, Week 2, 6, 14, 24, 48, and 60 ]
    Magnitude of Hepatitis B antigen-specific cellular immune responses will be assessed by ICS.

  5. Number of TriGrid Delivery System (TDS)-Intramuscular (IM) v2.0 Device Fault Conditions by Type [ Time Frame: Day 1, Week 4 and 12 ]
    Number of TDS-IM v2.0 device fault conditions by type will be observed. User reported fault conditions will be documented to enable assessment of the device reliability. Device functions to be assessed include electrode/needle deployment, study treatment administration, and electroporation application.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has chronic hepatitis B virus envelope antigen (HBeAg) negative hepatitis B virus (HBV) infection documented by a positive hepatitis B virus surface antigen (HBsAg) test and/or detectable HBV deoxyribonucleic acid (DNA) at least 6 months prior to the screening visit
  • Is on a stable treatment with one of the approved oral nucleos(t)ide analogs (NA) polymerase inhibitors tenofovir alafenamide, tenofovir disoproxil fumarate, or entecavir for greater than or equal to (>=)12 months prior to screening. A history of switching between the above treatments is acceptable as long as it was not triggered by virologic failure
  • Must demonstrate HBV DNA levels less than (<)60 international unit/milliliter (IU/mL) on 2 occasions separated by greater than (>)6 months (of which one can be the screening assessment).
  • Has HBsAg levels at screening between 100 IU/mL and 10,000 IU/mL
  • Has normal alanine aminotransferase (ALT) levels for at least 6 months prior to baseline with no documented measurement exceeding 1.25 times upper limit of normal [ULN]). Minimal requirement is documentation of two ALT results within the year prior to baseline of which one can be the screening assessment.

Exclusion Criteria:

  • Presence of advanced hepatic fibrosis or cirrhosis in 1 of the assessments below done less than or equal to (<=)6 month prior to baseline: a. Metavir score 3 or 4 in a liver biopsy OR b. Fibroscan result of >9 kilopascal (kPa) OR c. Acoustic Radiation Force Impulse (ARFI) result of >=1.55 meter/second (m/s)
  • Clinical signs or history of liver cirrhosis or hepatic decompensation:

    1. Metavir score 4 in a historical biopsy OR
    2. ascites, esophageal varices, or hepatic encephalopathy OR
    3. documentation of one of the following laboratory abnormality:

    i. direct (conjugated) bilirubin >1.2 times upper limit of normal (ULN) OR ii. prothrombin time (PT) >1.2 times ULN OR iii. serum albumin <3.5 gram per deciliter (g/dL)

  • Positive serology test at screening for any of the following:

    1. anti-hepatitis B surface (ant-HBs) antibodies
    2. HBeAg
    3. anti-human immunodeficiency virus (HIV)-1 or anti-HIV-2 antibodies
    4. anti-hepatitis A virus (HAV) immunoglobulin M (IgM) antibodies
    5. anti-hepatitis C virus (ant-HCV) antibodies
    6. anti-hepatitis D virus (anti-HDV) antibodies
  • Participants with any evidence of liver disease of non-HBV etiology. This includes but is not limited to hepatitis A, C, or D virus infections (as above), drug- or alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, α-1 antitrypsin deficiency, primary biliary cirrhosis, primary sclerosing cholangitis, non-alcoholic steatohepatitis or any other non-HBV liver disease considered clinically significant by the investigator
  • Has a history of persistent or recurrent hyperbilirubinemia unless explained by known Gilbert's Disease
  • History of blood disorders (bleeding problems or a blood clot, thalassemia major or sickle cell anemia).
  • History of severe local or systemic reactions to any vaccination or a history of severe allergic reactions.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03463369


Contacts
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

Locations
Belgium
ZiekenhuisNetwerk Antwerpen (ZNA) - Stuivenberg Not yet recruiting
Antwerp, Belgium
Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc Not yet recruiting
Brussels, Belgium
Universite Libre de Bruxelles (ULB) - Hopital Erasme Not yet recruiting
Brussels, Belgium
University Hospital, Ghent Not yet recruiting
Ghent, Belgium
Germany
Ruprecht-Karls-Universität Heidelberg Not yet recruiting
Mannheim, Baden-Wuerttemberg, Germany, 68167
Principal Investigator: Matthias Ebert         
Universität Regensburg Not yet recruiting
Regensburg, Bavaria, Germany, 92053
Principal Investigator: Kilian Weigand         
Medizinische Hochschule Hannover Not yet recruiting
Hannover, Lower Saxony, Germany, 30625
Principal Investigator: Markus Cornberg         
Universitätsklinikum Essen Not yet recruiting
Essen, North Rhine-Westphalia, Germany, 45122
Principal Investigator: Gudrun Hilgard         
Universitätsklinikum Leipzig Not yet recruiting
Leipzig, Sasxony, Germany, 04103
Principal Investigator: Thomas Berg         
Zentrum fuer Infektiologie Berlin Prenzlauer Berg (ZIBP) Not yet recruiting
Berlin, Germany, 10439
Principal Investigator: Axel Baumgarten         
EPIMED - Gesellschaft für epidemiologische und klinische Forschung in der Medizin mbH Not yet recruiting
Berlin, Germany, 12157
Principal Investigator: Keikawus Arasteh         
Klinikum Joh.Wolfg.Goethe-UNI Zentrum d. Inneren Medizin Not yet recruiting
Frankfurt, Germany, 60596
Principal Investigator: Stefan Zeuzem         
Institut fuer Interdisziplinaere Medizin (IFI) Not yet recruiting
Hamburg, Germany, 20099
Principal Investigator: Peter Buggisch         
Universitätsklinikum Tuebingen (UKT) Not yet recruiting
Tubingen, Germany, 72076
Principal Investigator: Christoph Berg         
United Kingdom
Queen Elizabeth Medical Center University Hospital Birmingham NHS Foundation Trust Not yet recruiting
Birmingham, United Kingdom, B15 2GW
Principal Investigator: David Mutimer         
Barts and The London School of Medicine and Dentistry, Blizzard Institute London Not yet recruiting
London, United Kingdom, E1 1BB
Principal Investigator: Patrick Kennedy         
Royal Free London NHS Foundation Trust Not yet recruiting
London, United Kingdom, NW3 2PF
Principal Investigator: Douglas MacDonald         
King's College Hospital Not yet recruiting
London, United Kingdom, SE5 9RS
Principal Investigator: Kosh Agarwal, MD         
Pennine Acute Hospitals Not yet recruiting
Manchester, United Kingdom, E1 1BB
Principal Investigator: Andrew Ustianowski         
Royal Surrey County Hospital NHS Foundation Trust Not yet recruiting
Watford, United Kingdom, GU2 7XX
Principal Investigator: Aftab Ala         
Sponsors and Collaborators
Janssen Sciences Ireland UC
Investigators
Study Director: Janssen Sciences Ireland UC Clinical Trial Janssen Sciences Ireland UC

Responsible Party: Janssen Sciences Ireland UC
ClinicalTrials.gov Identifier: NCT03463369     History of Changes
Other Study ID Numbers: 64300535HPB1001
64300535HPB1001 ( Other Identifier: Janssen Sciences Ireland UC )
2017-000147-41 ( EudraCT Number )
First Posted: March 13, 2018    Key Record Dates
Last Update Posted: March 29, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs