Phase 2
N=24
A Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Chronic Hepatitis B Virus Infection
Hepatitis B
Bottom Line
View on ClinicalTrials.gov: NCT04585789 ↗Enrolled (actual)
24
Serious AEs
2.1%
Results posted
Mar 2024
Primary outcome: Primary: Panel 1 and 2: Absolute Change From Baseline in the Percentage of Hepatitis B Surface Antigen (HBsAg) Hepatocytes at Week 40 — -78.46; -5.68 percentage of HBsAg hepatocytes
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- JNJ-73763989 (Drug); JNJ-56136379 (Drug); Entecavir (ETV) (Drug); Tenofovir disoproxil (Drug); Tenofovir alafenamide (TAF) (Drug); PegIFN-alpha-2a (Optional) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Janssen Research & Development, LLC
- Primary completion
- Feb 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Panel 1 and 2: Absolute Change From Baseline in the Percentage of Hepatitis B Surface Antigen (HBsAg) Hepatocytes at Week 40 |
-78.46; -5.68 | — |
| PRIMARY Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and JNJ-87719164 [M65; Deaminated Metabolite of JNJ-73763976]) at Week 12 |
3550.00; 87300.00; 66175.00 | — |
| PRIMARY Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, and JNJ-73763924 and JNJ-87719164 [M65; Deaminated Metabolite of JNJ-73763976]) at Week 40 |
5883.33; 208666.67; 133800.00 | — |
| PRIMARY Panel 3: Plasma Concentration of JNJ-73763989 (JNJ-73763976, and JNJ-73763924) at Week 12 |
254.70; 36.18 | — |
| PRIMARY Panel 3: Plasma Concentrations of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) at Week 40 |
530.97; 74.87 | — |
| PRIMARY Panel 3: Correlation of Liver Concentration to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of JNJ-87719164 (M65: Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 12 |
14.51; 2844.26; 19.47 | — |
| PRIMARY Panel 3: Correlation of Liver to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of JNJ-87719164 (M65: Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 40 |
12.67; 2847.66; 22.65 | — |
| SECONDARY Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 2 at Follow-up Week 48 |
50.0; 42.9; 50.0 | — |
| SECONDARY Panel 1, 2 and 3: Percentage of Participants Who Achieved HBsAg Seroclearance |
25.0; 20.0; 0 | — |
| SECONDARY Panel 1, 2 and 3: Percentage of Participants Who Achieved HBeAg Seroclearance |
37.5; 50.0 | — |
| SECONDARY Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Hepatitis B Core Antigen Positive (HBcAg+) Hepatocytes at Week 40 |
-54.49; 0.03 | — |
| SECONDARY Panel 1,and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Covalently Closed Circular Deoxyribonucleic Acid Positive (cccDNA+) Hepatocytes at Week 40 |
-4.50; -2.40 | — |
| SECONDARY Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: HBsAg Positive (HBsAg+) Hepatocytes at Week 40 |
-92.38; -14.19 | — |
| SECONDARY Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Pre-genomic Ribonucleic Acid Positive (pgRNA+) Hepatocytes at Week 40 |
-81.23; -6.74 | — |
| SECONDARY Panel 1 and 2: Change From Baseline in Transcriptional Activity (Ratio of pg RNA/cccDNA) at Week 40 |
50.00; 8.86 | — |
| SECONDARY Panel 1, 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Silent Infected Hepatocytes at Week 40 |
25.06; 2.88 | — |
| SECONDARY Panel 1, 2 and 3: Percentage of Participants With HBsAg Seroclearance at Week 72 Without Restarting Nucleos(t)Ide Analog (NA) Treatment |
0; 1; 0 | — |
| SECONDARY Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 1 at Follow-up Week 48 |
50.0; 70.0; 50.0 | — |
| SECONDARY Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 3 at Follow-up Week 48 |
25.0; 42.9; 50.0 | — |
| SECONDARY Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 4 at Follow-up Week 48 |
11.1; 0; 0; 22.2; 30.0; 25.0 | — |
| SECONDARY Panel 1, 2 and 3: Percentage of Participants Who Achieved HBsAg Seroconversion |
28.6; 11.1; 0 | — |
| SECONDARY Panel 1, 2 and 3: Percentage of Participants Who Achieved HBeAg Seroconversion |
28.6; 50.0 | — |
| SECONDARY Panel 1, 2 and 3: Percentage of Participants With Off-treatment Virologic Flares Per Derivation 1 |
0; 0; 33.3; 0; 0; 50.0 | — |
| SECONDARY Panel 1, 2 and 3: Percentage of Participants With Off-treatment and On-treatment Biochemical Flares |
0; 0; 10.0; 10.0; 25.0 | — |
| SECONDARY Panel 1, 2 and 3: Percentage of Participants With Off-treatment Clinical Flares |
0; 0; 0; 0; 0; 50.0 | — |
| SECONDARY Panel 1, 2 and 3: Time to First Occurence of HBsAg Seroclearance |
NA; NA; NA | — |
| SECONDARY Panel 1, 2 and 3: Percentage of Participants With Virologic Breakthrough |
0; 0; 0 | — |
| SECONDARY Panel 1, 2 and 3: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) |
90.0; 100.0; 75.0; 50.0; 60.0; 75.0 | — |
| SECONDARY Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses |
6; 6; 0; 0; 1; 1 | — |
| SECONDARY Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests |
0; 10.0; 25.0; 0; 10.0; 25.0 | — |
| SECONDARY Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) |
0; 10.0; 0; 0; 10.0; 0 | — |
| SECONDARY Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High) Treatment-emergent DAIDS Toxicity Grade in Vital Signs |
0; 10.0; 0; 0; 0; 0 | — |
| SECONDARY Panel 1, 2 and 3: Number of Participants With Clinically Significant Treatment-emergent Abnormalities in Physical Examination |
4; 0; 0; 0; 0; 0 | — |
| SECONDARY Panel 2 and 3: Plasma Trough Concentration (C[0hour]) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) |
NA; NA; NA; NA | — |
| SECONDARY Panel 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) |
2757; 1062; 595; 205 | — |
| SECONDARY Panel 3: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) |
924; 178 | — |
| SECONDARY Panel 2 and 3: Minimum Observed Plasma Concentration (Cmin) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) |
NA; NA; NA; NA | — |
| SECONDARY Panel 2: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976,JNJ-73763924) |
6.00; 10.00; 6.00; 10.00 | — |
| SECONDARY Panel 3:Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) |
6.00; 5.04 | — |
| SECONDARY Panel 2: Area Under the Plasma Concentration-time Curve From Time Zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) |
27744; 13820; 5388; 2649 | — |
| SECONDARY Panel 3: Area Under the Plasma Concentration-time Curve From Time Zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) |
13,256; 2,394 | — |
Summary
The purpose of this study is to assess changes in intrahepatic hepatitis B surface antigen (HBsAg) between baseline and on-treatment liver biopsy in response to JNJ-3989-based combination treatment.
Eligibility Criteria
Inclusion Criteria
- Medically stable on the basis of physical examination, medical history, vital signs, and triplicate 12-lead electrocardiogram (ECG) performed at screening
- Hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening: participants be either currently not treated with HBeAg positive status or virologically (nucleos[t]ide analog [NA]) suppressed with HBeAg negative status
- Hepatitis B surface antigen (HBsAg) greater than (>) 100 International Units per Milliliter (IU/mL) at screening
- Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included
- Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential
- Fibroscan liver stiffness measurement less than and equal to ( =) 1.1* upper limit of normal (ULN); (b) Partial thromboplastin time >1.1*ULN; (c) Any signs of prolonged bleeding (>10 minutes)
- Presence of hemoglobinopathy (including sickle cell disease, thalassemia)
- Liver biopsy performed prior to screening that led to complications and that in the opinion of the investigator would prohibit another liver biopsy
Data sourced from ClinicalTrials.gov (NCT04585789). 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.