Clinical trial 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis B, Chronic
Lead sponsor: Janssen Sciences Ireland UC
Sponsor class: INDUSTRY
First posted: 2018-03-13
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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.


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.

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs) by Severity and Relationship to Study Treatment and Dose Level
timeFrame: Up to Week 16
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Up to Week 16
measure: Number of Participants With Clinically Significant Changes in Vital Signs
timeFrame: Up to Week 16
measure: Number of Participants With Clinically Significant Changes in Physical Examination (Palpation of Lymph Nodes, Height, Body Weight, and Skin Examination) Findings
timeFrame: Up to Week 16
measure: Number of Participants With Acute Injection Site Reactions on Day 1
timeFrame: From 0 to 2 hours post-vaccination on Day 1
measure: Number of Participants With Acute Injection Site Reactions at Week 4
timeFrame: From 0 to 2 hours post-vaccination at Week 4
measure: Number of Participants With Acute Injection Site Reactions at Week 12
timeFrame: From 0 to 2 hours post-vaccination at Week 12
measure: Number of Participants With Injection Site Reactions After Vaccination on Day 1
timeFrame: Up to 7 days post-vaccination on Day 1
measure: Number of Participants With Injection Site Reactions After Vaccination on Week 4
timeFrame: Up to 7 days post-vaccination on Week 4
measure: Number of Participants With Injection Site Reactions After Vaccination on Week 12
timeFrame: Up to 7 days post-vaccination on Week 12
Secondary outcomes:
measure: Percentage of Participants With a Positive Hepatitis B Virus (HBV) Specific T Cells Response
timeFrame: Day 1, Week 2, 6, 14, 24, 48, and 60
measure: Time to Detection of HBV Specific T-Cell Responses
timeFrame: Day 1 up to Week 60
measure: Percentage of CD4+ and CD8+ T-Cell Responses
timeFrame: Day 1, Week 2, 6, 14, 24, 48, and 60
measure: Hepatitis B Antigen-Specific Cellular Immune Response
timeFrame: Day 1, Week 2, 6, 14, 24, 48, and 60
measure: Number of TriGrid Delivery System (TDS)-Intramuscular (IM) v2.0 Device Fault Conditions by Type
timeFrame: Day 1, Week 4 and 12
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: ZiekenhuisNetwerk Antwerpen (ZNA) - Stuivenberg
city: Brussels
country: Belgium
facility: Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc
city: Brussels
country: Belgium
facility: Universite Libre de Bruxelles (ULB) - Hopital Erasme
city: Mannheim
country: Germany
facility: Ruprecht-Karls-U Mannheim
state: Baden-Wuerttemberg
city: Hannover
country: Germany
facility: MH Hannover
state: Lower Saxony
city: UK Essen
country: Germany
facility: Universitätsklinikum Essen
state: North Rhine-Westphalia
city: Hamburg
country: Germany
facility: IFI Hamburg
city: Leipzig
country: Germany
facility: UK Leipzig
city: Regensburg
country: Germany
facility: Universität Regensburg
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth - Birmingham
city: London
country: United Kingdom
facility: Royal Free - London
city: London
country: United Kingdom
facility: King's College - London
city: London
country: United Kingdom
facility: Bart's Health - Blizard Inst. London
city: Manchester
country: United Kingdom
facility: Pennine Acute Hospitals - Manchester
Study officials:
affiliation: Janssen Sciences Ireland UC
name: Janssen Sciences Ireland UC Clinical Trial
role: STUDY_DIRECTOR
References: