NCT03463369 - 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 | Crick

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 Years

Medical Language ↔ Plain English

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 within 12 months of screening: 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.

Locations (14)

ZiekenhuisNetwerk Antwerpen (ZNA) - Stuivenberg

Antwerp, Belgium

Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc

Brussels, Belgium

Universite Libre de Bruxelles (ULB) - Hopital Erasme

Brussels, Belgium

Ruprecht-Karls-U Mannheim

Mannheim, Baden-Wurttemberg, Germany

MH Hannover

Hanover, Lower Saxony, Germany

Universitätsklinikum Essen

UK Essen, North Rhine-Westphalia, Germany

IFI Hamburg

Hamburg, Germany

UK Leipzig

Leipzig, Germany

Universität Regensburg

Regensburg, Germany

Queen Elizabeth - Birmingham

Birmingham, United Kingdom

...and 4 more locations

Outcomes

Primary Outcomes

Number of Participants with Adverse Events (AEs) by Severity and Relationship to Study Treatment and Dose Level

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.

Time frame: Up to Week 16

Number of Participants With Laboratory Abnormalities

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.

Time frame: Up to Week 16

Number of Participants With Clinically Significant Changes in Vital Signs

Number of participants with clinically significant changes in the vital signs including blood pressure, pulse/heart rate, and body temperature will be reported.

Time frame: Up to Week 16

Number of Participants With Clinically Significant Changes in Physical Examination (Palpation of Lymph Nodes, Height, Body Weight, and Skin Examination) Findings

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.

Time frame: Up to Week 16

Number of Participants With Acute Injection Site Reactions 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.

Time frame: From 0 to 2 hours post-vaccination on Day 1

Number of Participants With Acute Injection Site Reactions at Week 4

Time frame: From 0 to 2 hours post-vaccination at Week 4

Number of Participants With Acute Injection Site Reactions at Week 12

Time frame: From 0 to 2 hours post-vaccination at Week 12

Number of Participants With Injection Site Reactions After 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.

Time frame: Up to 7 days post-vaccination on Day 1

Number of Participants With Injection Site Reactions After 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.

Time frame: Up to 7 days post-vaccination on Week 4

Number of Participants With Injection Site Reactions After Vaccination on Week 12

Time frame: Up to 7 days post-vaccination on Week 12

Secondary Outcomes

Percentage of Participants With a Positive Hepatitis B Virus (HBV) Specific T Cells Response

Percentage of participants with a positive HBV-specific T cells response, assessed by interferon (IFN)-gamma ELISpot assay will be reported.

Time frame: Day 1, Week 2, 6, 14, 24, 48, and 60

Time to Detection of HBV Specific T-Cell Responses

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.

Time frame: Day 1 up to Week 60

Percentage of CD4+ and CD8+ T-Cell Responses

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).

Time frame: Day 1, Week 2, 6, 14, 24, 48, and 60

Hepatitis B Antigen-Specific Cellular Immune Response

Magnitude of Hepatitis B antigen-specific cellular immune responses will be assessed by ICS.

Time frame: Day 1, Week 2, 6, 14, 24, 48, and 60

Number of TriGrid Delivery System (TDS)-Intramuscular (IM) v2.0 Device Fault Conditions by Type

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.

Time frame: Day 1, Week 4 and 12

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

Overview

Conditions

Interventions

Eligibility

Locations (14)

Outcomes

Primary Outcomes

Secondary Outcomes