A Study of Different Combination Regimens Including JNJ-73763989 and/or JNJ-56136379 for the Treatment of Chronic Hepatitis B Virus Infection
- Conditions
- Hepatitis B, Chronic
- Interventions
- Drug: JNJ-73763989Drug: Placebo for JNJ-73763989Drug: Placebo for JNJ-56136379Drug: JNJ-56136379Drug: Nucleos(t)ide Analog (NA)
- Registration Number
- NCT03982186
- Lead Sponsor
- Janssen Sciences Ireland UC
- Brief 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.
- Detailed Description
Hepatitis B virus (HBV) is a small deoxyribonucleic acid virus that specifically infects the human liver. The acute phase of infection is either followed by an immune controlled state or progresses to chronic hepatitis B. The worldwide estimated prevalence of chronic HBV infection is about 292 million people affected. Hepatitis B surface antigen (HBsAg) seroclearance is currently considered to be associated with the most thorough suppression of HBV replication (termed functional cure). With current available NA treatment strategies, rate of HBsAg seroclearance remains very low (around 3 percent \[%\]) even under long-term treatment. Also, with the persistently high global prevalence of HBV-associated mortality, there is a medical need for more effective finite treatment options that lead to sustained HBsAg seroclearance. JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic HBV infection via ribonucleic acid interference mechanism. JNJ-56136379 is an orally administered capsid assembly modulator that is being developed for the treatment of chronic HBV infection. The aim of the study is to evaluate efficacy as measured by proportion of participants who completed 48-week study intervention and qualified for stopping NA treatment at Week 48. The study includes: Screening phase (4 weeks), Double-blind study intervention phase (from Day 1 up to Week 48), and Follow-up phase (48 weeks after end of investigational intervention with a maximum duration of 96 weeks). The duration of individual study participation will be between 100 and 150 weeks. Safety and tolerability (including adverse events \[AEs\] and Serious AEs, laboratory assessments, electrocardiogram \[ECG\], vital signs, physical examination), efficacy (including HBsAg seroclearance), and pharmacokinetics will be assessed throughout the study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 471
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 4: JNJ-73763989 (low dose) + Placebo + NA Placebo for JNJ-56136379 Participants will receive low dose of JNJ-73763989 along with placebo for JNJ-56136379 and NA (either ETV, TDF, or TAF) up to 48 weeks. Arm 1: JNJ-73763989 (medium dose) + JNJ-56136379 + NA JNJ-73763989 Participants will receive medium dose of JNJ-73763989 along with JNJ-56136379 and nucleos(t)ide analog (NA) treatment (either entecavir \[ETV\], tenofovir disoproxil fumarate \[TDF\], or tenofovir alafenamide \[TAF\]) up to 48 weeks. Arm 1: JNJ-73763989 (medium dose) + JNJ-56136379 + NA Nucleos(t)ide Analog (NA) Participants will receive medium dose of JNJ-73763989 along with JNJ-56136379 and nucleos(t)ide analog (NA) treatment (either entecavir \[ETV\], tenofovir disoproxil fumarate \[TDF\], or tenofovir alafenamide \[TAF\]) up to 48 weeks. Arm 2: JNJ-73763989 (high dose) + Placebo + NA Placebo for JNJ-56136379 Participants will receive high dose of JNJ-73763989 along with placebo for JNJ-56136379 and NA (either ETV, TDF, or TAF) up to 48 weeks. Arm 2: JNJ-73763989 (high dose) + Placebo + NA Nucleos(t)ide Analog (NA) Participants will receive high dose of JNJ-73763989 along with placebo for JNJ-56136379 and NA (either ETV, TDF, or TAF) up to 48 weeks. Arm 3: JNJ-73763989 (medium dose) + Placebo + NA Placebo for JNJ-56136379 Participants will receive medium dose of JNJ-73763989 along with placebo for JNJ-56136379 and NA (either ETV, TDF, or TAF) up to 48 weeks. Arm 4: JNJ-73763989 (low dose) + Placebo + NA JNJ-73763989 Participants will receive low dose of JNJ-73763989 along with placebo for JNJ-56136379 and NA (either ETV, TDF, or TAF) up to 48 weeks. Arm 6 (Control): Placebo + Placebo + NA Placebo for JNJ-56136379 Participants will receive placebo for JNJ-73763989 and placebo for JNJ-56136379 along with NA (either ETV, TDF, or TAF) up to 48 weeks. Arm 2: JNJ-73763989 (high dose) + Placebo + NA JNJ-73763989 Participants will receive high dose of JNJ-73763989 along with placebo for JNJ-56136379 and NA (either ETV, TDF, or TAF) up to 48 weeks. Arm 3: JNJ-73763989 (medium dose) + Placebo + NA JNJ-73763989 Participants will receive medium dose of JNJ-73763989 along with placebo for JNJ-56136379 and NA (either ETV, TDF, or TAF) up to 48 weeks. Arm 4: JNJ-73763989 (low dose) + Placebo + NA Nucleos(t)ide Analog (NA) Participants will receive low dose of JNJ-73763989 along with placebo for JNJ-56136379 and NA (either ETV, TDF, or TAF) up to 48 weeks. Arm 5: Placebo + JNJ-56136379 + NA Placebo for JNJ-73763989 Participants will receive placebo for JNJ-73763989 and a fixed dose of JNJ-56136379 along with NA (either ETV, TDF, or TAF) up to 48 weeks. Arm 6 (Control): Placebo + Placebo + NA Placebo for JNJ-73763989 Participants will receive placebo for JNJ-73763989 and placebo for JNJ-56136379 along with NA (either ETV, TDF, or TAF) up to 48 weeks. Arm 1: JNJ-73763989 (medium dose) + JNJ-56136379 + NA JNJ-56136379 Participants will receive medium dose of JNJ-73763989 along with JNJ-56136379 and nucleos(t)ide analog (NA) treatment (either entecavir \[ETV\], tenofovir disoproxil fumarate \[TDF\], or tenofovir alafenamide \[TAF\]) up to 48 weeks. Arm 3: JNJ-73763989 (medium dose) + Placebo + NA Nucleos(t)ide Analog (NA) Participants will receive medium dose of JNJ-73763989 along with placebo for JNJ-56136379 and NA (either ETV, TDF, or TAF) up to 48 weeks. Arm 5: Placebo + JNJ-56136379 + NA JNJ-56136379 Participants will receive placebo for JNJ-73763989 and a fixed dose of JNJ-56136379 along with NA (either ETV, TDF, or TAF) up to 48 weeks. Arm 5: Placebo + JNJ-56136379 + NA Nucleos(t)ide Analog (NA) Participants will receive placebo for JNJ-73763989 and a fixed dose of JNJ-56136379 along with NA (either ETV, TDF, or TAF) up to 48 weeks. Arm 6 (Control): Placebo + Placebo + NA Nucleos(t)ide Analog (NA) Participants will receive placebo for JNJ-73763989 and placebo for JNJ-56136379 along with NA (either ETV, TDF, or TAF) up to 48 weeks.
- Primary Outcome Measures
Name Time Method Percentage of Participants Meeting the Nucleos(t)Ide Analog (NA) Treatment Completion Criteria at Week 48 Week 48 Percentage of participants meeting the NA treatment completion criteria at Week 48 were reported. A participant was defined as a responder in meeting the NA treatment completion criteria at Week 48, if the following criteria were met based on the clinical laboratory tests performed at Week 44: participants had alanine transaminase (ALT) less than (\<) 3\*upper limit of normal range (ULN); had hepatitis B virus deoxyribonucleic acid (HBV DNA) \< lower limit of quantification (LLOQ); was hepatitis B e antigen (HBeAg)-negative; had hepatitis B surface antigen (HBsAg) \<10 international units per milliliter (IU/mL). Multiple Imputation using a longitudinal multiple regression model was applied to impute missing data.
- Secondary Outcome Measures
Name Time Method Follow-up Phase 1: Percentage of Participants With SAEs From Week 48 up to Week 96 An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE was any untoward medical occurrence that at any dose may result in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, and was medically important.
Time to Achieve HBsAg Seroclearance Baseline (Day 1) up to Week 96 Time to HBsAg seroclearance (defined as HBsAg level \<LLOQ \[0.05 IU/mL\]) was defined as the number of days between the date of first study treatment intake and the date of the first occurrence of HBsAg seroclearance.
Time to Achieve HBeAg Seroclearance Baseline (Day 1) up to Week 96 Time to HBeAg seroclearance (defined as HBeAg level \<LLOQ \[0.11 IU/mL\]) was defined as the number of days between the date of first study treatment intake and the date of the first occurrence of HBeAg seroclearance.
Percentage of Participants With HBsAg Levels <100 IU/mL Baseline, Weeks 12, 24, 48, 60, 72, 96 Percentage of participants with HBsAg levels \<100 IU/mL was reported.
Percentage of Participants With Undetectable HBV DNA Levels After Re-start of NA Treatment During Follow-up Week 48 up to Week 96 Percentage of participants with undetectable HBV DNA levels after re-start of NA treatment during follow-up was reported.
Follow-up Phase 1: Percentage of Participants With TEAEs From Week 48 up to Week 96 An AE was any untoward medical occurrence in a clinical study participants administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Treatment-emergent AEs were defined as AEs with onset or worsening on or after date of first dose of study treatment.
Extended Follow-up Phase: Percentage of Participants With TEAEs Extended Follow up Week 1 to extended follow up Week 48 An AE was any untoward medical occurrence in a clinical study participants administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Treatment-emergent AEs were defined as AEs with onset or worsening on or after date of first dose of study treatment.
Double-blind Phase: Percentage of Participants With Serious Adverse Events (SAEs) Baseline up to Week 48 An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE was any untoward medical occurrence that at any dose may result in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, and was medically important.
Extended Follow-up Phase: Percentage of Participants With SAEs Extended Follow up Week 1 to extended follow up Week 48 An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE was any untoward medical occurrence that at any dose may result in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, and was medically important.
Double-blind Phase: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) Baseline up to Week 48 An AE was any untoward medical occurrence in a clinical study participants administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Treatment-emergent AEs were defined as AEs with onset or worsening on or after date of first dose of study treatment.
Percentage of Participants With HBsAg Seroclearance 48 Weeks After Completion of All Study Intervention at Week 48 Week 96 Percentage of participants with HBsAg seroclearance 48 weeks after completion of all study intervention at Week 48 were reported. HBsAg Seroclearance was defined as HBsAg \<LLOQ (0.05 IU/mL). A responder was defined as a participant who achieved HBsAg seroclearance at Week 96 if the participant completed 48 weeks of treatment, met the criteria for stopping NA treatment at Week 48, did not require NA re-treatment between Week 48 and Week 96, and had HBsAg seroclearance at Week 96. Multiple Imputation using a longitudinal multiple regression model was applied to impute missing data.
Follow-up Phase 2: Percentage of Participants With TEAEs From Week 48 up to Week 96 An AE was any untoward medical occurrence in a clinical study participants administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Treatment-emergent AEs were defined as AEs with onset or worsening on or after date of first dose of study treatment.
Follow-up Phase 3: Percentage of Participants With TEAEs From Week 48 up to Week 96 An AE was any untoward medical occurrence in a clinical study participants administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Treatment-emergent AEs were defined as AEs with onset or worsening on or after date of first dose of study treatment.
Percentage of Participants With Abnormalities in Clinical Laboratory Tests (Hematology) Double blind (DB) phase: Baseline (Day 1) up to Week 48, Follow up (FU) phase: Week 48 up to Week 96 Percentage of participants with abnormalities in clinical laboratory tests (hematology: Abnormally low \[AL\] and Abnormally high \[AH\] basophils, eosinophils, erthrocytes mean corpuscular hemoglobin concentration, erthrocytes mean corpuscular heamoglobin, erthrocytes mean corpuscular volume, erthrocytes, hematocrit, lymphocytes atypical, metamyelocytes, monocytes, myelocytes, neutrophils, segmented, reticulocytes) were reported. Abnormality was determined at the investigator's discretion. Here, M.C: Mean corpuscular. Participants with abnormally low or high values were reported.
Percentage of Participants With Abnormalities in Vital Signs Double blind (DB) phase: Baseline (Day 1) up to Week 48, Follow up (FU) phase: Week 48 up to Week 96 Percentage of participants with abnormalities in vital signs parameters (pulse rate, diastolic and systolic blood pressure) were reported. Abnormality criteria: Pulse rate AL:\<=45 bpm; Systolic blood pressure (SBP) AL: \<=90 millimeters of mercury (mmHg), mild:\>140 mmHg to \<160 mmHg; moderate:\>=160 mmHg to \<180 mmHg; Diastolic blood pressure (DBP): AL: \<=150 mmHg; mild:\>90 mmHg to \<100 mmHg; moderate: \>=100 mmHg to \<110 mmHg; severe:\>=110 mmHg. Abnormality was determined at the investigator's discretion. Participants with abnormally low or high values were reported.
Follow-up Phase 2: Percentage of Participants With SAEs From Week 48 up to Week 96 An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE was any untoward medical occurrence that at any dose may result in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, and was medically important.
Follow-up Phase 3: Percentage of Participants With SAEs From Week 48 up to Week 96 An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE was any untoward medical occurrence that at any dose may result in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, and was medically important.
Percentage of Participants With Abnormalities in Electrocardiogram (ECG) Double blind (DB) phase: Baseline (Day 1) up to Week 48, Follow up (FU) phase: Week 48 up to Week 96 Percentage of participants with abnormalities in ECG parameters (heart rate, PR interval, QRS duration, and QTcF interval) were reported. Abnormality criteria: Heart rate abnormally low (AL): \<45 beats per minute (bpm); PR interval AH:\>220 msec; QRS duration AH:\>120 msec; QTcF borderline prolonged (BP) QT: 450 msec to \<=480 msec. Participants with abnormally low or high values were reported.
Percentage of Participants With HBV DNA <LLOQ 24 and 48 Weeks After Completion of All Study Intervention at Week 48 Weeks 72 and 96 Percentage of participants with HBV DNA \<LLOQ at 24 and 48 weeks after completion of all study intervention at Week 48 were reported. A responder was defined as a participant who achieved HBV DNA \<LLOQ 24 and 48 weeks after stopping all study treatments at any time during the study and without restarting NA treatment thereafter.
Percentage of Participants With HBsAg Seroclearance After Completion of NA Treatment at Weeks 60, 84, and 96 Weeks 60, 84, and 96 Percentage of participants with HBsAg seroclearance after completion of NA treatment at Weeks 60, 84, and 96 were reported. Seroclearance of HBsAg was defined as HBsAg level \<LLOQ (0.05 IU/mL). For Week 60: a responder was defined as a participant who achieved HBsAg seroclearance 12 weeks off treatment if the subject achieved HBsAg seroclearance 12 weeks after stopping; for Week 84:A responder was defined as a participant who achieved HBsAg seroclearance 36 weeks off-treatment if the participant achieved HBsAg seroclearance 36 weeks after stopping all study treatments; for Week 96:A responder was defined as a participant who achieved HBsAg seroclearance at Week 96 if the participant completed 48 weeks of treatment, met the criteria for stopping NA treatment at Week 48, did not require NA re-treatment between Week 48 and Week 96, and had HBsAg seroclearance at Week 96.
Change From Baseline in HBeAg Levels Baseline, Weeks 12, 24, 48, 60, 72, 96 Change from baseline in HBeAg levels was reported.
Percentage of Participants With Abnormalities in Clinical Laboratory Tests (Chemistry) Double blind (DB) phase: Baseline up to Week 48, Follow up (FU) phase: Week 48 up to Week 96 Percentage of participants with abnormalities in clinical laboratory tests (Chemistry: abnormally high and serum alpha fetoprotein, serum chloride, Serum gamma glutamyl tranferase \[GGT\], Serum high density cholesterol \[HDL\] Cholesterol, Indirect Bilirubin, Lactate Dehydrogenase, Serum Protein, Urea Nitrogen) were reported. Abnormality was determined at the investigator's discretion. Participants with abnormally low or high values were reported.
Percentage of Participants With Abnormalities in Clinical Laboratory Tests (Urinalysis) Double blind (DB) phase: Baseline up to Week 48, Follow up (FU) phase: Week 48 up to Week 96 Percentage of participants with abnormalities in clinical laboratory tests(Urinalysis: abnormally high and low urine granular casts, urine hyaline casts, Urine Leukocytes,Urine Specific Gravity,Urine Squamous Epithelial cell, Urine T.E Cells, Urine Transitinoal erythrocyte count \[E.C\],Urine Tubular erthrocyte count ) were reported. Abnormality was determined at the investigator's discretion. Participants with abnormally low or high values were reported.
Percentage of Participants With HBsAg Seroclearance 24 Weeks After Completion of All Study Intervention at Week 48 Week 72 Percentage of participants with HBsAg seroclearance 24 weeks after completion of all study intervention at Week 48 were reported. HBsAg seroclearance was defined as HBsAg (less than \[\<\] lower limit of quantification LLOQ \[0.05 IU/mL\]). Responder was defined as a participant who achieved functional cure at Week 72. A participant was defined as having achieved functional cure at Week 72 if he/she: had met the criteria for stopping NA treatment at Week 48 and stopped treatment; had HBsAg seroclearance at Week 72 (that is, 24 weeks after stopping all study interventions); did not require NA re-treatment between Weeks 48 and 72. Multiple Imputation using a longitudinal multiple regression model was applied to impute missing data.
Percentage of Participants With HBsAg Seroconversion Weeks 48, 60, 72, and 96 HBsAg seroconversion was defined as achieving HBsAg seroclearance (HBsAg \[quantitative\] \<LLOQ \[0.05 IU/mL\]) together with an appearance of anti-HBs antibodies (baseline anti-HBs antibodies \[quantitative\] \<LLOQ and a post-baseline assessment greater than or equal to \[\>=\] LLOQ).
Change From Baseline in HBV DNA Levels Baseline, Weeks 12, 24, 48, 60, 72, 96 Change from baseline in HBV DNA levels were reported.
Percentage of Participants With HBV DNA Levels <LLOQ Baseline, Weeks 12, 24, 48, 60, 72, 96 Percentage of participants with HBV DNA levels \<LLOQ (20 IU/mL) were reported.
Percentage of Participants With ALT Normalization Baseline, Weeks 12, 24, 48, 60, 72, 96 Percentage of participants with ALT normalization was reported. A participant with ALT elevation at baseline was considered to achieve ALT normalization if his/her ALT value was \<ULN at any given postbaseline analysis time point. A participant was defined as on treatment failure if he/she never met the criteria for stopping NA treatment during the study. A participant was defined as off-treatment failure if he/she required NA re-treatment after stopping all study interventions.
Percentage of Participants Meeting the NA Treatment Completion Criteria During Follow-up Week 48 up to Week 96 Percentage of participants meeting the NA treatment completion criteria during follow-up were reported. A participant was defined as a responder in meeting the NA treatment completion criteria at Week 48, if the following criteria were met based on the clinical laboratory tests performed at Week 44: participants had alanine transaminase (ALT) less than (\<) 3\*upper limit of normal range (ULN); had hepatitis B virus deoxyribonucleic acid (HBV DNA) \< lower limit of quantification (LLOQ); was hepatitis B e antigen (HBeAg)-negative; had hepatitis B surface antigen (HBsAg) \<10 international units per milliliter (IU/mL). A responder was defined as a participant who stopped NA at Week 48 and met the NA treatment completion criteria at any time during the follow-up phase, regardless of the treatment duration.
Percentage of Participants Who Required NA Re-treatment During Follow-up Week 48 up to Week 96 Percentage of participants who required NA re-treatment during follow-up were reported. Responder was defined as a participant who met the criteria for NA re-treatment at any time during follow-up, for those participants who met the NA treatment completion criteria at any time during the study and actually stopped NA treatment. NA re-treatment criteria: (1) Re-start NA treatment immediately with signs of decreasing liver function based on laboratory findings (eg, International Normalized Ratio \[INR\], direct bilirubin) or clinical assessment (eg, ascites, hepatic encephalopathy). (2) Immediately with an HBV DNA value of \>100,000 IU/mL (irrespective of confirmation and/or ALT increase). (3) With confirmed post-treatment HBeAg seroreversion (HBeAg positive after it was negative at NA completion) (4) With confirmed\* post-treatment increases in HBV DNA \>2,000 IU/mL and ALT \>5x ULN (5) With confirmed\* post-treatment increases in HBV DNA \>20,000 IU/mL.
Percentage of Participants With Flares Follow-up phase (Week 48 up to Week 96) Percentage of participants with flares (virologic, biochemical, and clinical) were reported. Virologic flare: confirmed HBV DNA \>peak threshold ( 20,000 IU/mL 2,000 IU/mL and 200 IU/mL); biochemical Flare: confirmed ALT and/or AST increase of 3\*ULN and 3\*nadir; clinical flare: confirmed HBV DNA \>peak threshold and confirmed ALT and/or AST increase of 3\*ULN and 3\*nadir. Virologic and clinical flare was assessed only for those participants who were off-treatment and had HBV DNA\<LLOQ at the last observed time point on all study treatments and biochemical flares was identified on treatment and off treatment, respectively. Each virologic flare was categorized based on the confirmed (i.e., two consecutive values) peak HBV DNA above any of the three thresholds within the start and end date of that flare as follows: 20,000 IU/mL 2,000 IU/mL and 200 IU/mL. A participant was defined as off-treatment failure if he/she required NA re-treatment after stopping all study interventions.
Number of Participants With (Sustained) Reduction, Suppression, and/or Seroclearance Considering Single and Multiple Marker Weeks 12, 24, 36 and 48 Number of participants with (sustained) reduction considering multiple markers were reported. HBV DNA results \<LLOQ were reported as: (a) target detected, that is, traces of HBV DNA were detected/found but were too low to be quantified, or (b) target not detected, that is, no traces of HBV DNA were detected/found. LLOQ value for HBV DNA was 20 IU/mL.
Percentage of Participants With HBeAg Seroconversion Weeks 48, 60, 72, and 96 HBeAg seroconversion was defined as achieving HBeAg seroclearance (HBeAg \[quantitative\] \<LLOQ) together with an appearance of anti-HBe antibodies (baseline anti-HBe antibodies \[qualitative\] with a "negative" result and a post-baseline assessment with "positive" result.
Change From Baseline in HBsAg Levels Baseline, Weeks 12, 24, 48, 60, 72, 96 Change from baseline in HBsAg levels was reported.
Percentage of Participants With HBsAg Levels >1 log10 IU/mL Reduction From Baseline Weeks 12, 24, 48, 60, 72, 96 Percentage of participants with HBsAg levels \>1 log10 IU/mL reduction from baseline was reported.
Percentage of HBeAg-positive Participants With HBeAg Levels <LLOQ Weeks 12, 24, 48, 60, 72, 96 Percentage of HBeAg-positive participants with HBeAg levels \<LLOQ were reported.
Percentage of HBeAg-positive Participants With HBeAg Levels >1 log10 IU/mL Weeks 12, 24, 48, 60, 72, 96 Percentage of HBeAg-positive partcipants with HBeAg levels \>1 log10 IU/mL were reported.
Mean Change From Baseline in ALT at EOT (Week 48) in Participants With Elevated ALT at Baseline Baseline and Week 48 Mean change from baseline in ALT at EOT (Week 48) in participants with elevated ALT at baseline were reported.
Percentage of Participants With Virologic Breakthrough Baseline (Day 1) up to Week 48 Virologic breakthrough was defined as having a confirmed on-treatment HBV DNA increase by \>1 log10 from nadir (that is, lowest value during treatment) or a confirmed HBV DNA level \>200 IU/mL in participants who had on-treatment HBV DNA level below the LLOQ (20 IU/mL). On-treatment was defined as the time period in which the participant received any of the study intervention.
Trial Locations
- Locations (108)
Medical Company Hepatolog Ltd
🇷🇺Samara, Russian Federation
Istanbul University Cerrahpasa Medical Faculty
🇹🇷Istanbul, Turkey
ID Clinic
🇵🇱Myslowice, Poland
Clinic of the Modern Medicine
🇷🇺Moscow, Russian Federation
Universitaetsklinikum Leipzig
🇩🇪Leipzig, Germany
Nanfang Hospital
🇨🇳Guangzhou, China
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
National Hospital Organization Nagasaki Medical Center
🇯🇵Nagasaki, Japan
Nagoya City University Hospital
🇯🇵Nagoya, Japan
The Hospital of Hyogo College of Medicine
🇯🇵Nishinomiya, Japan
Hospital Sultanah Bahiyah
🇲🇾Alor Setar, Malaysia
University of Alberta - Faculty of Medicine & Dentistry
🇨🇦Edmonton, Alberta, Canada
UZ Antwerpen
🇧🇪Edegem, Belgium
Fukui-ken Saiseikai Hospital
🇯🇵Fukui City, Japan
University of Calgary
🇨🇦Calgary, Alberta, Canada
Fukuyama City Hospital
🇯🇵Fukuyama, Japan
Hokkaido University Hospital
🇯🇵Sapporo-shi, Japan
Hospital Selayang
🇲🇾Batu Caves, Malaysia
Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza w Bydgoszczy
🇵🇱Bydgoszcz, Poland
Smolensk Regional Clinical Hospital
🇷🇺Smolensk, Russian Federation
Stavropol State Medical University
🇷🇺Stavropol, Russian Federation
Prince Of Songkla University
🇹🇭Songkla, Thailand
Cliniques Universitaires Saint Luc
🇧🇪Bruxelles, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Tokyo Medical and Dental University Hospital
🇯🇵Bunkyo Ku, Japan
Chiba University Hospital
🇯🇵Chiba, Japan
Hiroshima University Hospital
🇯🇵Hiroshima shi, Japan
GI Research Institute (G.I.R.I.)
🇨🇦Vancouver, British Columbia, Canada
Kagawa Prefectural Central Hospital
🇯🇵Kagawa, Japan
Nara Medical University Hospital
🇯🇵Kashihara, Japan
Chiang Mai University Hospital
🇹🇭Chiang Mai, Thailand
Johns Hopkins Office of Capital Region Research - Sibley Memorial Hospital
🇺🇸Washington, District of Columbia, United States
I.D. Care, Inc.
🇺🇸Hillsborough, New Jersey, United States
Musashino Red Cross Hospital
🇯🇵Musashino, Japan
Osaka University Hospital
🇯🇵Suita-shi, Japan
Fujita Health University Hospital
🇯🇵Toyoake, Japan
Ural State Medical University
🇷🇺Chelyabinsk, Russian Federation
Republican Clinical Infectious Hospital
🇷🇺Saint Petersburg, Russian Federation
King Chulalongkorn Memorial Hospital
🇹🇭Bangkok, Thailand
Toranomon Hospital
🇯🇵Tokyo, Japan
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
St. Petersburg City Center for AIDS and Infectious Diseases Treatment and Prophylaxis
🇷🇺Saint Petersburg, Russian Federation
Southern California GI and Liver Center
🇺🇸San Clemente, California, United States
The Office of Franco Felizarta, MD
🇺🇸Bakersfield, California, United States
Ruane Clinical Research Group Inc
🇺🇸Los Angeles, California, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
NYU Hepatology Associates
🇺🇸New York, New York, United States
UZA-SGS
🇧🇪Edegem, Belgium
Fundacao de Medicina Tropical Doutor Heitor Vieira Dourado - FMT
🇧🇷Manaus, Brazil
Hospital Das Clinicas Da Faculdade De Medicina Da USP
🇧🇷Sao Paulo, Brazil
Universidade Federal da Bahia - Hospital Professor Edgard Santos
🇧🇷Salvador, Brazil
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
FN Hradec Kralove
🇨🇿Hradec Kralove, Czechia
RESEARCH SITE s.r.o.
🇨🇿Plzen, Czechia
Hopital Beaujon
🇫🇷Clichy, France
KLIN MED s.r.o
🇨🇿Praha 2, Czechia
IKEM
🇨🇿Praha, Czechia
CHU de Grenoble Hopital Albert Michallon
🇫🇷Grenoble, France
Hopital de La Croix Rousse
🇫🇷Lyon, France
Hopital Saint Joseph
🇫🇷Marseille, France
CHU de Nantes hotel Dieu
🇫🇷Nantes, France
Hopital Paul Brousse
🇫🇷Villejuif, France
Hopital Saint-Antoine
🇫🇷Paris, France
EPIMED GmbH
🇩🇪Berlin, Germany
Chu Rennes Hopital Pontchaillou
🇫🇷Rennes, France
Universitatsklinikum Essen
🇩🇪Essen, Germany
ICH Study Center GmbH & Co. KG
🇩🇪Hamburg, Germany
Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1
🇩🇪Frankfurt, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
🇩🇪Mainz, Germany
Azienda Ospedaliera Universitaria Policlinico G. Martino
🇮🇹Messina, Italy
Irccs Ospedale Maggiore Di Milano
🇮🇹Milano, Italy
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Azienda Ospedaliero-Universitaria di Modena, Ospedale di Baggiovara
🇮🇹Modena, Italy
Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma
🇮🇹Rome, Italy
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital University Sains Malaysia
🇲🇾Kota Bharu, Malaysia
Neutrum Lekarze M.Hlebowicz i Partnerzy spolka partnerska
🇵🇱Gdansk, Poland
Wojewodzki Szpital Zakazny w Warszawie
🇵🇱Warszawa, Poland
SP ZOZ Wroclawskie Centrum Zdrowia
🇵🇱Wroclaw, Poland
Sverdlovsk Regional Clinical Hospital #1
🇷🇺Ekaterinburg, Russian Federation
Krasnoyarsk Regional Center For AIDS And Infectious Diseases Treatment And Prophylaxis
🇷🇺Krasnoyarsk, Russian Federation
Medical Center SibNovoMed LLC
🇷🇺Novosibirsk, Russian Federation
Clinical Infectious Diseases Hospital n. a. S.P. Botkin
🇷🇺Saint-Petersburg, Russian Federation
Siriraj Hospital
🇹🇭Bangkok, Thailand
Hosp Clinic de Barcelona
🇪🇸Barcelona, Spain
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain
Hosp. Univ. Vall D Hebron
🇪🇸Barcelona, Spain
Hosp. Gral. Univ. Valencia
🇪🇸Valencia, Spain
Hosp. Univ. Marques de Valdecilla
🇪🇸Santander, Spain
Hacettepe University Hospital
🇹🇷Ankara, Turkey
Ankara University Medical Faculty
🇹🇷Ankara, Turkey
Ankara Bilkent Sehir Hastanesi
🇹🇷Ankara, Turkey
Ege University Medical of Faculty, Department of Gastroenterology
🇹🇷Izmir, Turkey
Kings College Hospital
🇬🇧London, United Kingdom
NHS Greater Glasgow and Clyde - Gartnavel General Hospital
🇬🇧Glasgow, United Kingdom
Karadeniz Teknik University Medical Faculty
🇹🇷Trabzon, Turkey
Grahame Hayton Unit
🇬🇧London, United Kingdom
St George's, University of London and St George's University Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Puerta De Hierro
🇪🇸Madrid, Spain
University Medical Center
🇩🇪Hamburg, Germany
Washington University School Of Medicine
🇺🇸Saint Louis, Missouri, United States
Vancouver ID Research and Care Centre Society
🇨🇦Vancouver, British Columbia, Canada
The University of Hong Kong
🇭🇰Hong Kong, Hong Kong
The Chinese University of Hong Kong
🇭🇰Shatin, Hong Kong