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

Hepatitis B, Chronic Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03463369
• Other study ID #: 64300535HPB1001
• Secondary ID: 64300535HPB10012
• Status: Completed
• Phase: Phase 1
• Start date: April 18, 2018
• Est. completion date: March 23, 2021

Study information

• Verified date: April 2021
• Source: Janssen Sciences Ireland UC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: March 23, 2021
• Est. primary completion date: March 23, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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, a-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.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Biological:
• JNJ-64300535
Participants will receive JNJ-64300535 vaccine by electroporation-mediated IM injection on Day 1, Week 4, and Week 12.
• 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.

Locations

Country	Name	City	State
Belgium	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
Germany	IFI Hamburg	Hamburg
Germany	MH Hannover	Hannover	Lower Saxony
Germany	UK Leipzig	Leipzig
Germany	Ruprecht-Karls-U Mannheim	Mannheim	Baden-Wuerttemberg
Germany	Universität Regensburg	Regensburg
Germany	Universitätsklinikum Essen	UK Essen	North Rhine-Westphalia
United Kingdom	Queen Elizabeth - Birmingham	Birmingham
United Kingdom	Bart's Health - Blizard Inst. London	London
United Kingdom	King's College - London	London
United Kingdom	Royal Free - London	London
United Kingdom	Pennine Acute Hospitals - Manchester	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Sciences Ireland UC

Countries where clinical trial is conducted

Belgium,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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-a] or IFN-? specific to any antigen) will be determined by Intracellular Cytokine Staining (ICS).	Day 1, Week 2, 6, 14, 24, 48, and 60
Secondary	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
Secondary	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