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Phase 2 Completed N=130 Randomized Double-blind Treatment

A Study of JNJ 73763989+JNJ 56136379+Nucleos(t)Ide Analog (NA) Regimen Compared to NA Alone in e Antigen Negative Virologically Suppressed Participants With Chronic Hepatitis B Virus Infection

Hepatitis B, Chronic
Source: ClinicalTrials.gov NCT04129554 ↗
Enrolled (actual)
130
Serious AEs
5.4%
Results posted
Jul 2024
Primary outcomePrimary: Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroclearance at Week 72 Without Restarting NA Treatment — 0.0; 0.0 Percentage of participants

Summary

The purpose of this study is to evaluate the efficacy of 48-week study intervention with JNJ-73763989+JNJ-56136379+nucleos(t)ide analog (NA) regimen compared to NA alone assessed by HBsAg levels. This study is part of HepB Wings Platform Trial (PLATFORMPAHPB2001).

Outcome Measures

OutcomeResultp-value
PRIMARY
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroclearance at Week 72 Without Restarting NA Treatment
0.0; 0.0
SECONDARY
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
85.9; 80.0
SECONDARY
Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs)
3.5; 8.9
SECONDARY
Percentage of Participants With HBsAg Seroclearance at Week 48
0; 0
SECONDARY
Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Less Than (<) Lower Limit of Quantification (LLOQ) at Week 48
97.3; 100
SECONDARY
Percentage of Participants With HBsAg Seroclearance at Week 96 (48 Weeks After Stopping All Study Interventions at Week 48 Without Restarting NA Treatment)
0.0; 0.0
SECONDARY
Percentage of Participants With (Sustained) Reduction, Suppression, and/or Seroclearance
23.9; 3.6; 64.8; 64.3
SECONDARY
Percentage of Participants With HBsAg Seroconversion at Week 96
0; 0
SECONDARY
Change From Baseline in HBsAg Values at Weeks 48, 72, and 96
-1.89; -0.06; -1.76; -0.25; -1.46; -0.49
SECONDARY
Change From Baseline in HBV DNA Values at Weeks 48, 72, and 96
SECONDARY
Time to Achieve First HBsAg Seroclearance
NA; NA
SECONDARY
Percentage of Participants With Reduction of More Than (>) 1 log10 IU/mL in HBsAg Levels From Baseline
81.5; 12.5
SECONDARY
Percentage of Participants With HBsAg Levels Less Than (<) 100 IU/mL at Weeks 48, 72, and 96
71.1; 2.4; 67.1; 10.3; 46.9; 15.0
SECONDARY
Percentage of Participants With HBV DNA Levels Less Than (<) LLOQ From Baseline up to Week 96 (End of Study)
23.9; 3.6
SECONDARY
Percentage of Participants With Flares
38.7; 25.0; 24.0; 30.0; 8.0; 10.0
SECONDARY
Percentage of Participants With Virologic Breakthrough
0.0; 0.0
SECONDARY
Percentage of Participants Requiring NA Re-Treatment During Follow-up
9.1; 26.8
SECONDARY
Correlation Coefficient Between On-treatment HBsAg Change From Baseline With On-treatment HBV Blood Markers and Baseline Characteristics
0.2860; 0.1746; 0.2381; 0.4324; -0.9970; -0.5923
SECONDARY
Observed Plasma Concentration at Predose (C[Predose]) of JNJ-73763976 (Molecule of JNJ-73763989)
NA
SECONDARY
Maximum Observed Analyte Concentration (Cmax) of JNJ-73763976 (Molecule of JNJ-73763989)
1111
SECONDARY
Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763976 (Molecule of JNJ-73763989)
6.00
SECONDARY
Observed Plasma Concentration at 24 Hour Postdose (C[24h]) of JNJ-73763976 (Molecule of JNJ-73763989)
275
SECONDARY
Area Under the Analyte Concentration Versus Time Curve From Time 0 to 24 Hours (AUC[0-24h]) of JNJ-73763976 (Molecule of JNJ-73763989)
17833
SECONDARY
Maximum Observed Analyte Concentration (Cmax) of JNJ-73763976 (Molecule of JNJ-73763989) Dose Normalized to 1 mg (Cmax[Dose Normalized])
8.34
SECONDARY
Area Under the Analyte Concentration Versus Time Curve From Time 0 to 24 Hours of JNJ-73763976 (Molecule of JNJ-73763989) Dose Normalized to 1 mg (AUC[0-24h], Dose Normalized)
134
SECONDARY
Observed Plasma Concentration at Predose (C[Predose]) of JNJ-73763924 (Molecule of JNJ-73763989)
NA
SECONDARY
Maximum Observed Analyte Concentration (Cmax) of JNJ-73763924 (Molecule of JNJ-73763989)
222
SECONDARY
Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763924 (Molecule of JNJ-73763989)
5.07
SECONDARY
Observed Plasma Concentration at 24 Hour Postdose (C[24h]) of JNJ-73763924 (Molecule of JNJ-73763989)
35.0
SECONDARY
Area Under the Analyte Concentration Versus Time Curve From Time 0 to 24 Hour (AUC[0-24h]) of JNJ-73763924 (Molecule of JNJ-73763989)
3386
SECONDARY
Maximum Observed Analyte Concentration (Cmax) of JNJ-73763924 (Molecule of JNJ-73763989) Dose Normalized to 1 mg (Cmax[Dose Normalized])
3.33
SECONDARY
Area Under the Analyte Concentration Versus Time Curve From Time 0 to 24 Hours of JNJ-73763924 (Molecule of JNJ-73763989) Dose Normalized to 1 mg (AUC[0-24h], Dose Normalized)
50.8
SECONDARY
Observed Plasma Concentration at Predose (C[Predose]) of JNJ-56136379
10812
SECONDARY
Maximum Observed Analyte Concentration (Cmax) of JNJ-56136379
14754
SECONDARY
Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-56136379
4.00
SECONDARY
Observed or Predicted Concentration at the End of a Dosing Interval (Ctau) of JNJ-56136379
12763
SECONDARY
Area Under the Analyte Concentration Versus Time Curve During a Dosing Interval at Steady State (AUCtau) of JNJ-56136379
282458

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 e (antigen) (HBeAg)-negative on stable nucleotide analogue (NA) treatment for at least 24 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 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
  • History or signs of cirrhosis or portal hypertension (nodules, no smooth liver contour, no normal portal vein, spleen size ≥12 cm) or 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
  • Known allergies, hypersensitivity, or intolerance to JNJ-73763989 and JNJ-56136379 or their excipients or to 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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04129554). 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.

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