Clinical trial NCT04585789: A Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Chronic Hepatitis B Virus Infection
Official title: A Phase 2 Randomized, Open-label, Parallel-group, Multicenter Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Response to Combination Regimens Containing JNJ-73763989 and Nucleos(t)Ide Analog With or Without JNJ-56136379 in Patients With Chronic Hepatitis B Virus Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis B
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-10-14
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: As per protocol amendment-5, JNJ-56136379 has been removed as study intervention and all participants are counted as single arm in each panel.
Primary purpose: OTHER

Brief 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.

Detailed description: The title of protocol reflects the original study design. The study design section is reflecting that the design as of protocol amendment 5 is non-randomized.

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 (\<=) 9 Kilopascal (kPa) within 6 months prior to screening or at the time of 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
* History or signs of cirrhosis or portal hypertension, signs of hepatocellular carcinoma (HCC) or clinically relevant renal abnormalities on an abdominal ultrasound performed within 6 months prior to screening or at the time of screening
* Presence of coagulopathy or bleeding disorder as indicated by: (a) International normalized ratio (INR) greater than or 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

Primary outcomes:
measure: Panel 1 and 2: Absolute Change From Baseline in the Percentage of Hepatitis B Surface Antigen (HBsAg) Hepatocytes at Week 40
timeFrame: Baseline, Week 40
measure: Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and JNJ-87719164 [M65; Deaminated Metabolite of JNJ-73763976]) at Week 12
timeFrame: At Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
measure: Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, and JNJ-73763924 and JNJ-87719164 [M65; Deaminated Metabolite of JNJ-73763976]) at Week 40
timeFrame: At Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
measure: Panel 3: Plasma Concentration of JNJ-73763989 (JNJ-73763976, and JNJ-73763924) at Week 12
timeFrame: At Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
measure: Panel 3: Plasma Concentrations of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) at Week 40
timeFrame: At Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
measure: 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
timeFrame: Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
measure: 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
timeFrame: Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
Secondary outcomes:
measure: Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 2 at Follow-up Week 48
timeFrame: Follow-up Week 48
measure: Panel 1, 2 and 3: Percentage of Participants Who Achieved HBsAg Seroclearance
timeFrame: Follow-up Week 48
measure: Panel 1, 2 and 3: Percentage of Participants Who Achieved HBeAg Seroclearance
timeFrame: Follow-up Week 48
measure: Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Hepatitis B Core Antigen Positive (HBcAg+) Hepatocytes at Week 40
timeFrame: Baseline, Week 40
measure: Panel 1,and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Covalently Closed Circular Deoxyribonucleic Acid Positive (cccDNA+) Hepatocytes at Week 40
timeFrame: Baseline, Week 40
measure: Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: HBsAg Positive (HBsAg+) Hepatocytes at Week 40
timeFrame: Baseline, Week 40
measure: Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Pre-genomic Ribonucleic Acid Positive (pgRNA+) Hepatocytes at Week 40
timeFrame: Baseline, Week 40
measure: Panel 1 and 2: Change From Baseline in Transcriptional Activity (Ratio of pg RNA/cccDNA) at Week 40
timeFrame: Baseline, Week 40
measure: Panel 1, 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Silent Infected Hepatocytes at Week 40
timeFrame: Baseline, Week 40
measure: Panel 1, 2 and 3: Percentage of Participants With HBsAg Seroclearance at Week 72 Without Restarting Nucleos(t)Ide Analog (NA) Treatment
timeFrame: At Week 72 (24 weeks after completion of all study drugs at Week 48)
measure: Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 1 at Follow-up Week 48
timeFrame: Follow-up Week 48
measure: Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 3 at Follow-up Week 48
timeFrame: From follow-up Week 24 up to follow-up Week 48
measure: Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 4 at Follow-up Week 48
timeFrame: Follow-up Week 48
measure: Panel 1, 2 and 3: Percentage of Participants Who Achieved HBsAg Seroconversion
timeFrame: From baseline (Day 1) up to follow-up Week 48
measure: Panel 1, 2 and 3: Percentage of Participants Who Achieved HBeAg Seroconversion
timeFrame: From baseline (Day 1) up to follow-up Week 48
measure: Panel 1, 2 and 3: Percentage of Participants With Off-treatment Virologic Flares Per Derivation 1
timeFrame: From baseline (Day 1) up to follow-up Week 48
measure: Panel 1, 2 and 3: Percentage of Participants With Off-treatment and On-treatment Biochemical Flares
timeFrame: From baseline (Day 1) up to follow-up Week 48
measure: Panel 1, 2 and 3: Percentage of Participants With Off-treatment Clinical Flares
timeFrame: From baseline (Day 1) up to follow-up Week 48
measure: Panel 1, 2 and 3: Time to First Occurence of HBsAg Seroclearance
timeFrame: From baseline (Day 1) up to follow-up Week 48
measure: Panel 1, 2 and 3: Percentage of Participants With Virologic Breakthrough
timeFrame: From baseline (Day 1) up to follow-up Week 48
measure: Panel 1, 2 and 3: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
measure: Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses
timeFrame: Open-label: Weeks 40, 44, and 48; Follow-up Phase: Follow-up Weeks 2, 12 and 24
measure: 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
timeFrame: Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
measure: Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG)
timeFrame: Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
measure: Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High) Treatment-emergent DAIDS Toxicity Grade in Vital Signs
timeFrame: Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
measure: Panel 1, 2 and 3: Number of Participants With Clinically Significant Treatment-emergent Abnormalities in Physical Examination
timeFrame: Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
measure: Panel 2 and 3: Plasma Trough Concentration (C[0hour]) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
timeFrame: Week 4 : Pre-dose on Day 29
measure: Panel 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
timeFrame: Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose
measure: Panel 3: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
timeFrame: Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose
measure: Panel 2 and 3: Minimum Observed Plasma Concentration (Cmin) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
timeFrame: Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose
measure: Panel 2: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976,JNJ-73763924)
timeFrame: Week 4 (Day 29): Post dose (15 minutes, 30 minutes, 1, 2, 3, 4, 6, and 24 hours)
measure: Panel 3:Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
timeFrame: Week 4 (Day 29): Post dose (15 minutes, 30 minutes, 1, 2, 3, 4, 6, and 24 hours)
measure: Panel 2: Area Under the Plasma Concentration-time Curve From Time Zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
timeFrame: Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose
measure: Panel 3: Area Under the Plasma Concentration-time Curve From Time Zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
timeFrame: Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Clichy
country: France
facility: Hopital Beaujon
city: Hamburg
country: Germany
facility: University Medical Center
city: Milano
country: Italy
facility: Irccs Ospedale Maggiore Di Milano
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research
city: Myslowice
country: Poland
facility: ID Clinic
city: London
country: United Kingdom
facility: Grahame Hayton Unit
city: London
country: United Kingdom
facility: Kings College Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: