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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Biological: Placebo; Drug: Nucleos(t)ide Analogs (NA); Biological: JNJ-64300535

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium
    • ZiekenhuisNetwerk Antwerpen (ZNA) - Stuivenberg
  • Brussels, Belgium
    • Université libre de Bruxelles (ULB) - Hôpital Erasme
  • Brussels, Belgium
    • Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc
• Germany
  • Hamburg, Germany
    • IFI Hamburg
  • Leipzig, Germany
    • UK Leipzig
  • Regensburg, Germany
    • Universitat Regensburg
  • Baden-Wuerttemberg
    • Mannheim, Baden-Wuerttemberg, Germany, 68167
      • Ruprecht-Karls-U Mannheim
  • Lower Saxony
    • Hannover, Lower Saxony, Germany, 30625
      • MH Hannover
  • North Rhine-Westphalia
    • UK Essen, North Rhine-Westphalia, Germany, 45122
      • Universitätsklinikum Essen
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • Queen Elizabeth - Birmingham
  • London, United Kingdom, NW3 2PF
    • Royal Free - London
  • London, United Kingdom, SE5 9RS
    • King's College - London
  • London, United Kingdom
    • Bart's Health - Blizard Inst. London
  • Manchester, United Kingdom, E1 1BB
    • Pennine Acute Hospitals - Manchester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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.	Drug: Nucleos(t)ide Analogs (NA); Participants will receive NA as a standard of care treatment.; Biological: JNJ-64300535; Participants will receive JNJ-64300535 vaccine by electroporation-mediated IM injection on Day 1, Week 4, and Week 12.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	From 0 to 2 hours post-vaccination on Day 1
Number of Participants With Acute Injection Site Reactions 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.	From 0 to 2 hours post-vaccination at Week 4
Number of Participants With Acute Injection Site Reactions 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.	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.	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.	Up to 7 days post-vaccination on Week 4
Number of Participants With Injection Site Reactions After 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.	Up to 7 days post-vaccination on Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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).	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.	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.	Day 1, Week 4 and 12

Collaborators and Investigators

• Sponsor: Janssen Sciences Ireland UC

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2018
• Primary Completion (Actual): March 23, 2021
• Study Completion (Actual): March 23, 2021

Study Registration Dates

• First Submitted: February 28, 2018
• First Submitted That Met QC Criteria: March 10, 2018
• First Posted (Actual): March 13, 2018

Study Record Updates

• Last Update Posted (Actual): April 14, 2021
• Last Update Submitted That Met QC Criteria: April 13, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic
• Other Study ID Numbers: 64300535HPB1001 (Other Identifier: Janssen Sciences Ireland UC); 2017-000147-41 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No