Phase 2
Completed N=232
An Efficacy, Safety, and Pharmacokinetics Study of JNJ-56136379 in Participants With Chronic Hepatitis B Virus Infection
Source: ClinicalTrials.gov NCT03361956 ↗Enrolled (actual)
232
Serious AEs
2.6%
Results posted
Nov 2022
Primary outcomePrimary: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels in Currently Not Treated Population at Week 24 — -0.251; -0.096; -0.142; -0.203 log10 IU per milliliter (log10 IU/mL)
Summary
The main purpose of this study is to evaluate efficacy of 24 weeks of study treatment, in terms of changes in hepatitis B surface antigen (HBsAg) levels.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels in Currently Not Treated Population at Week 24 |
-0.251; -0.096; -0.142; -0.203; -0.411; 0.015 | — |
| PRIMARY Change From Baseline in HBsAg Levels in Virologically Suppressed Population at Week 24 |
0.008; -0.063; 0.105; 0.024; -0.017; 0.092 | — |
| SECONDARY Number of Participants With Treatment- Emergent Adverse Events (AEs) |
34; 18; 55; 25; 54 | — |
| SECONDARY Number of Participants With Serious Adverse Events (SAEs) |
1; 1; 4; 0; 4 | — |
| SECONDARY Number of Participants With Clinically Significant Changes in Vital Signs, Physical Examinations, Electrocardiogram (ECG), and Clinical Laboratory Tests |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Change From Baseline in HBsAg Levels in Currently Not Treated Population Over Time |
-0.251; -0.096; -0.142; -0.203; -0.411; 0.015 | — |
| SECONDARY Change From Baseline in HBsAg Levels in Virologically Suppressed Population Over Time |
0.008; -0.063; 0.105; 0.024; -0.017; 0.092 | — |
| SECONDARY Percentage of Participants With HBsAg Levels Less Than (<) 1,000 or <100 International Units Per Milliliter (IU/mL) in Currently Not Treated Population |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With HBsAg Levels <1,000 or <100 IU/mL in Virologically Suppressed Population |
0; 0; 0; 20.0; 11.1; 10.0 | — |
| SECONDARY Percentage of Participants With Greater Than (>) 0.5 log10 IU/mL or >1 log10 IU/mL Reduction in HBsAg From Baseline in Currently Not Treated Population |
12.5; 12.5; 8.3; 28.6; 36.4; 0 | — |
| SECONDARY Percentage of Participants With >0.5 log10 IU/mL or >1 log10 IU/mL Reduction in HBsAg From Baseline in Virologically Suppressed Population |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels in Currently Not Treated Population |
-5.211; -3.284; -5.531; -5.719; -5.883; -3.622 | — |
| SECONDARY Change From Baseline in HBV DNA Levels in Virologically Suppressed Population |
-0.051; 0.000; 0.021; -0.032; 0.016; -0.024 | — |
| SECONDARY Percentage of Participants With Undetectable HBV DNA Levels in Currently Not Treated Population |
0; 0; 0; 0; 9.1; 23.1 | — |
| SECONDARY Percentage of Participants With Undetectable HBV DNA Levels in Virologically Suppressed Population |
40.0; 22.2; 40.0; 60.0; 58.3; 63.2 | — |
| SECONDARY Change From Baseline in HBeAg Levels in Currently Not Treated Population |
-0.811; -0.456; -0.487; -0.974; -0.701; -2.250 | — |
| SECONDARY Change From Baseline in HBeAg Levels in Virologically Suppressed Population |
-0.313; -0.315; -0.162; -0.589; -0.393; -0.291 | — |
| SECONDARY Percentage of Participants With >0.5 log10 IU/mL and >1 log10 IU/mL Reduction in HBeAg From Baseline in Currently Not Treated Population |
62.5; 50; 41.7; 78.6; 63.6; 37.5 | — |
| SECONDARY Percentage of Participants With >0.5 log10 IU/mL and >1 log10 IU/mL Reduction in HBeAg From Baseline in Virologically Suppressed Population |
20; 33.3; 10; 20; 11.1; 0 | — |
| SECONDARY Percentage of Participants With HBsAg Seroclearance in Currently Not Treated Population |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With HBsAg Seroclearance in Virologically Suppressed Population |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With HBsAg Seroconversion in Currently Not Treated Population |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With HBsAg Seroconversion in Virologically Suppressed Population |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Percentage of Participants With Normalized Alanine Aminotransferase (ALT) Levels in Currently Not Treated Population |
62.5; 60.0; 54.5; 64.3; 44.4; 55.6 | — |
| SECONDARY Percentage of Participants With Normalized ALT Levels in Virologically Suppressed Population |
100.0; 33.3; 50.0; 100.0; 0; 100.0 | — |
| SECONDARY Percentage of Participants With Virological Breakthrough in Currently Not Treated Population |
0; 16.7; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Virological Breakthrough in Virologically Suppressed Population |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Plasma Concentrations of Entecavir [ETV] in Currently Not Treated Population |
NA; NA; NA; NA; 1.39; 1.18 | — |
| SECONDARY Plasma Concentrations of ETV in Virologically Suppressed Population |
NA; 0.683; NA; 1.86; 1.89; 1.94 | — |
| SECONDARY Plasma Concentrations of Tenofovir Disoproxil Fumarate (TDF) in Currently Not Treated Population |
NA; NA; NA; NA; 277; 170 | — |
| SECONDARY Plasma Concentrations of TDF in Virologically Suppressed Population |
NA; NA; 68.9; 63.3; 274; 311 | — |
| SECONDARY Plasma Concentrations of JNJ-56136379 in Currently Not Treated Population |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Plasma Concentrations of JNJ-56136379 in Virologically Suppressed Population |
NA; NA; NA; 857; 616; 2103 | — |
| SECONDARY Number of Participants With Treatment-Associated Mutations |
8; 0; 4; 0; 2; 0 | — |
Eligibility Criteria
Inclusion Criteria
- Participants must have a body mass index (weight in kilogram (kg) divided by the square of height in meters) of 18.0 to 35.0 kilogram / square meter (kg/m^2), extremes included
- Participants must have chronic hepatitis B virus infection (CHB) infection documented by: Serum hepatitis B surface antigen (HBsAg)-positive at screening and serum HBsAg- or hepatitis B virus (HBV) deoxyribonucleic acid (DNA)-positive at least 6 months prior to screening; Serum immunoglobulin M (IgM) anti- hepatitis B core-related (HBc) antibody negative at screening
- In participants currently not being treated (Treatment Arms 1-2-3 and 6-7-8): Participants must not be receiving any CHB treatment at screening, that is, Have never received treatment with HBV antiviral medicines, including NAs or interferon (IFN) products, OR Have not been on treatment with HBV antiviral medicines, including nucleos(t)ide analog (NA)s or IFN products within 6 months prior to baseline (first intake of study drugs), and participants must be HBeAg-positive and have HBV DNA greater than or equal to (>=) 20,000 International Units Per Milliliter (IU/mL), OR be hepatitis B e antigen (HBeAg)-negative and have HBV DNA >=2,000 IU /mL at screening, and participants must have HBsAg greater than (>) 250 IU/mL at screening, and participants must have alanine aminotransferase (ALT) > upper limit of normal (ULN) and less than or equal to ( =12 months prior to screening, and participants must have HBsAg > 250 IU/mL at screening, and participants must have ALT 1.2* ULN, or International normalized ratio (INR) >1.5* ULN, or Serum albumin < lower limit of normal (LLN), or documented history or current evidence of variceal bleeding, ascites, or hepatic encephalopathy
- Participants with a history of cardiac arrhythmia (example, extrasystoli, tachycardia at rest), history of risk factors for Torsades de Pointes syndrome (example, hypokalemia, family history of long QT syndrome) or history or other clinical evidence of significant or unstable cardiac disease (example, angina, congestive heart failure, myocardial infarction, diastolic dysfunction, significant arrhythmia, coronary heart disease, and/or clinically significant 12 lead electrocardiograms (ECGs) abnormalities), moderate to severe valvular disease, or uncontrolled hypertension at screening
- Participants with contraindications to the use of ETV or TDF per local prescribing information
Substudy:
- Presence of coagulopathy or hemoglobinopathy (including sickle cell disease, thalassemia)
- Use of any anti-coagulant, anti-platelet, or non-steroidal anti-inflammatory drug medications from 10 days before until 5 days after each liver biopsy
- Presence of ascites, focal liver lesions, and other findings that would be contraindications for liver biopsies
Data sourced from ClinicalTrials.gov (NCT03361956). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.