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

NCT03463369 | Completed Phase 1 DMC

• 2 other identifiers: 64300535HPB10012017-000147-41
• Study Type: interventional
• Target: 30
• Locations: 3 countries
• Sites: 14

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.

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (5)

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

  Day 1, Week 2, 6, 14, 24, 48, and 60

• Time to Detection of HBV Specific T-Cell Responses

  Day 1 up to Week 60

• Percentage of CD4+ and CD8+ T-Cell Responses

  Day 1, Week 2, 6, 14, 24, 48, and 60

• Hepatitis B Antigen-Specific Cellular Immune Response

  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

  Day 1, Week 4 and 12

Study Arms (2)

Placebo + Nucleos(t)ide Analogs (NA)

EXPERIMENTAL

Participants will receive placebo intramuscular (IM) injection on Day 1, Week 4, and Week 12, along with standard of care NA treatment.

Biological: Placebo; Drug: Nucleos(t)ide Analogs (NA)

JNJ-64300535 + NA

EXPERIMENTAL

Participants will receive JNJ-64300535 IM injection on Day 1, Week 4, and Week 12, along with standard of care NA treatment.

Biological: JNJ-64300535; Drug: Nucleos(t)ide Analogs (NA)

Interventions

JNJ-64300535 BIOLOGICAL

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

JNJ-64300535 + NA

Placebo BIOLOGICAL

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.

Placebo + Nucleos(t)ide Analogs (NA)

Nucleos(t)ide Analogs (NA) DRUG

Participants will receive NA as a standard of care treatment.

JNJ-64300535 + NA; Placebo + Nucleos(t)ide Analogs (NA)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Metavir score 4 in a historical biopsy OR
• ascites, esophageal varices, or hepatic encephalopathy OR
• 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:
• anti-hepatitis B surface (ant-HBs) antibodies
• HBeAg
• anti-human immunodeficiency virus (HIV)-1 or anti-HIV-2 antibodies
• anti-hepatitis A virus (HAV) immunoglobulin M (IgM) antibodies
• anti-hepatitis C virus (ant-HCV) antibodies
• 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

Sponsors & Collaborators

• Janssen Sciences Ireland UC: lead

Study Sites (14)

ZiekenhuisNetwerk Antwerpen (ZNA) - Stuivenberg

Antwerp, Belgium

Location

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

Brussels, Belgium

Location

Universite Libre de Bruxelles (ULB) - Hopital Erasme

Brussels, Belgium

Location

Ruprecht-Karls-U Mannheim

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

MH Hannover

Hanover, Lower Saxony, 30625, Germany

Location

Universitätsklinikum Essen

UK Essen, North Rhine-Westphalia, 45122, Germany

Location

IFI Hamburg

Hamburg, Germany

Location

UK Leipzig

Leipzig, Germany

Location

Universität Regensburg

Regensburg, Germany

Location

Queen Elizabeth - Birmingham

Birmingham, B15 2GW, United Kingdom

Location

Royal Free - London

London, NW3 2PF, United Kingdom

Location

King's College - London

London, SE5 9RS, United Kingdom

Location

Bart's Health - Blizard Inst. London

London, United Kingdom

Location

Pennine Acute Hospitals - Manchester

Manchester, E1 1BB, United Kingdom

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Janssen Sciences Ireland UC Clinical Trial

  Janssen Sciences Ireland UC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2018
• First Posted: March 13, 2018
• Study Start: April 18, 2018
• Primary Completion: March 23, 2021
• Study Completion: March 23, 2021
• Last Updated: April 14, 2021

Record last verified: 2021-04

Locations

BE (3); DE (6); GB (5)