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 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.


Eligibility 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 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.