Phase 2
Completed N=471
A Study of Different Combination Regimens Including JNJ-73763989 and/or JNJ-56136379 for the Treatment of Chronic Hepatitis B Virus Infection
Hepatitis B, Chronic
Source: ClinicalTrials.gov NCT03982186 ↗
Enrolled (actual)
471
Serious AEs
2.8%
Results posted
Jul 2024
Primary outcomePrimary: Percentage of Participants Meeting the Nucleos(t)Ide Analog (NA) Treatment Completion Criteria at Week 48 — 9.4; 19.1; 16.3; 5.5 Percentage of participants — p== 0.848
Summary
The purpose of this study is to establish the dose-response relationship for antiviral activity of 3 dose levels of JNJ-73763989+nucleos(t)ide analog (NA) and to evaluate the efficacy of combination regimens of JNJ-73763989+NA (with and without JNJ-56136379) and of JNJ-56136379+NA.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Meeting the Nucleos(t)Ide Analog (NA) Treatment Completion Criteria at Week 48 |
9.4; 19.1; 16.3; 5.5; 0.0; 2.2 | = 0.848 |
| SECONDARY Double-blind Phase: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) |
71.6; 64.6; 71.0; 74.2; 85.4; 66.7 | — |
| SECONDARY Follow-up Phase 1: Percentage of Participants With TEAEs |
48.1; 45.7; 56.3; 44.7; 55.3; 31.8 | — |
| SECONDARY Follow-up Phase 2: Percentage of Participants With TEAEs |
37.5; 29.4; 60.0; 60.0; 0 | — |
| SECONDARY Follow-up Phase 3: Percentage of Participants With TEAEs |
33.3; 37.5; 20.0 | — |
| SECONDARY Extended Follow-up Phase: Percentage of Participants With TEAEs |
66.7; 71.4; 100.0 | — |
| SECONDARY Double-blind Phase: Percentage of Participants With Serious Adverse Events (SAEs) |
2.1; 3.1; 2.2; 1.1; 4.2; 0 | — |
| SECONDARY Follow-up Phase 1: Percentage of Participants With SAEs |
1.2; 7.1; 4.2; 1.2; 2.1; 0 | — |
| SECONDARY Follow-up Phase 2: Percentage of Participants With SAEs |
12.5; 0; 0; 0; 0 | — |
| SECONDARY Follow-up Phase 3: Percentage of Participants With SAEs |
33.3; 0; 0 | — |
| SECONDARY Extended Follow-up Phase: Percentage of Participants With SAEs |
0; 14.3; 40.0 | — |
| SECONDARY Percentage of Participants With Abnormalities in Clinical Laboratory Tests (Hematology) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Abnormalities in Clinical Laboratory Tests (Chemistry) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Abnormalities in Clinical Laboratory Tests (Urinalysis) |
0; 0; 100.0; 100.0; 0; 0 | — |
| SECONDARY Percentage of Participants With Abnormalities in Electrocardiogram (ECG) |
0; 2.1; 1.1; 3.3; 0; 0 | — |
| SECONDARY Percentage of Participants With Abnormalities in Vital Signs |
1.1; 4.2; 2.2; 2.2; 0; 0 | — |
| SECONDARY Percentage of Participants With HBsAg Seroclearance 24 Weeks After Completion of All Study Intervention at Week 48 |
0.0; 0.0; 0.0; 0.0; 0.0; 2.2 | — |
| SECONDARY Percentage of Participants With HBsAg Seroclearance 48 Weeks After Completion of All Study Intervention at Week 48 |
0.0; 1.1; 0.0; 0.0; 0.0; 2.2 | — |
| SECONDARY Percentage of Participants With HBV DNA <LLOQ 24 and 48 Weeks After Completion of All Study Intervention at Week 48 |
5.3; 16.0; 7.6; 1.1; 0.0; 4.4 | — |
| SECONDARY Percentage of Participants Meeting the NA Treatment Completion Criteria During Follow-up |
11.7; 27.7; 16.3; 4.4; 0.0; 2.2 | — |
| SECONDARY Percentage of Participants With HBsAg Seroclearance After Completion of NA Treatment at Weeks 60, 84, and 96 |
0.0; 9.1; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Percentage of Participants Who Required NA Re-treatment During Follow-up |
1.1; 1.1; 2.2; 0.0; 0.0; 0.0 | — |
| SECONDARY Percentage of Participants With Flares |
0.0; 0.0; 0.0; 0.0; 2.1; 0.0 | — |
| SECONDARY Number of Participants With (Sustained) Reduction, Suppression, and/or Seroclearance Considering Single and Multiple Marker |
0; 1; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With HBsAg Seroconversion |
0.0; 1.1; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Percentage of Participants With HBeAg Seroconversion |
4.0; 3.6; 8.7; 0; 0; 18.2 | — |
| SECONDARY Change From Baseline in HBsAg Levels |
3.66; 3.83; 3.70; 3.81; 3.63; 3.83 | — |
| SECONDARY Change From Baseline in HBeAg Levels |
1.22; 1.60; 1.68; 1.26; 0.81; 1.03 | — |
| SECONDARY Change From Baseline in HBV DNA Levels |
5.97; 6.64; 6.34; 6.10; 6.48; 6.39 | — |
| SECONDARY Time to Achieve HBsAg Seroclearance |
NA; NA; NA | — |
| SECONDARY Time to Achieve HBeAg Seroclearance |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Percentage of Participants With HBsAg Levels <100 IU/mL |
0; 1.1; 1.1; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With HBsAg Levels >1 log10 IU/mL Reduction From Baseline |
40.2; 72.8; 60.5; 27.3; 2.2; 0 | — |
| SECONDARY Percentage of HBeAg-positive Participants With HBeAg Levels <LLOQ |
7.4; 3.7; 17.4; 6.9; 7.7; 0 | — |
| SECONDARY Percentage of HBeAg-positive Participants With HBeAg Levels >1 log10 IU/mL |
33.3; 33.3; 39.1; 3.4; 23.1; 10.0 | — |
| SECONDARY Percentage of Participants With HBV DNA Levels <LLOQ |
64.4; 60.4; 63.7; 60.9; 60.6; 63.8 | — |
| SECONDARY Mean Change From Baseline in ALT at EOT (Week 48) in Participants With Elevated ALT at Baseline |
-72.77; -65.47; -37.51; -42.53; -17.68; -49.28 | — |
| SECONDARY Percentage of Participants With ALT Normalization |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Virologic Breakthrough |
2.1; 2.1; 2.2; 2.2; 0.0; 2.2 | — |
| SECONDARY Percentage of Participants With Undetectable HBV DNA Levels After Re-start of NA Treatment During Follow-up |
1.1; 1.1; 1.1; 0.0; 0.0; 0.0 | — |
Eligibility Criteria
Inclusion Criteria
- Medically stable based on physical examination, medical history, vital signs, electrocardiogram (ECG) at screening
- Chronic hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening
- 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
- Liver fibrosis stage 0-2 (Metavir) or Fibroscan less than (<) 9 Kilopascal (kPa) at screening
Exclusion Criteria
- Evidence of infection with hepatitis A, C, D or E virus infection or evidence of human immunodeficiency, virus type 1 (HIV-1) or HIV-2 infection at screening
- History or evidence of clinical signs/symptoms of hepatic decompensation including but not limited to: portal hypertension, ascites, hepatic encephalopathy, esophageal varices or any laboratory abnormalities indicating a reduced liver function as defined in the protocol
- Evidence of liver disease of non-HBV etiology
- Signs of hepatocellular carcinoma (HCC)
- Significant laboratory abnormalities as defined in the protocol at screening
- Participants with a history of malignancy within 5 years before screening
- Abnormal sinus rhythm or ECG parameters at screening as defined in the protocol
- History of or current cardiac arrhythmia or history or clinical evidence of significant or unstable cardiac disease
- Participants with any current or previous illness for which, in the opinion of the investigator and/or sponsor, participation would not be in the best interest of the participant
- History of or current clinically significant skin disease or drug rash
- Participants with known allergies, hypersensitivity, or intolerance to JNJ-3989 and JNJ 6379 or their excipients or excipients of the placebo content
- Contraindications to the use of entecavir (ETV), tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) per local prescribing information
- Participants who have taken any therapies disallowed per protocol
- Female participants who are pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 90 days after the last dose of study intervention
- Male participants who plan to father a child while enrolled
- Participants who had or planned major surgery, (example, requiring general anesthesia) or who have received an organ transplant
- Vulnerable participants (example, incarcerated individuals, individuals under a legal protection measure)
Data sourced from ClinicalTrials.gov (NCT03982186). 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.