Chronic Hepatitis B Virus Infection MedDRA version: 20.1 Level: PT Classification code 10008910 Term: Chronic hepatitis B System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: JNJ-73763989
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Not yet assigned
Other descriptive name: JNJ-73763989-AAM
Concentration unit: mg/ml milligram(s)/millilitre
Sponsors
Janssen Sciences Ireland UC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult male or female participants =18 (or the legal age of consent in the jurisdiction in which the study is taking place) to 65 years of age, inclusive. 2. Participants must be medically stable, with the exception of HBV disease, on the basis of physical examination, medical history, vital signs, and 12-lead ECG performed at screening. If there are abnormalities, they must be consistent with the underlying illness in the study population. This determination must be recorded in the participant’s source documents and initialed by the investigator. 3. Participants must have chronic HBV infection documented by serum HBsAg positivity at screening. In addition, chronicity must be documented by serum HBsAg positivity at least 6 months prior to screening or alternative markers of chronicity (HBeAg positivity or HBV DNA positivity at least 6 months prior to screening, ALT elevation above ULN at least 6 months prior to screening without another cause than HBV infection, liver biopsy, or documented transmission event at least 6 months prior to screening). Note: if documentation of chronicity (as mentioned above) at least 6 months prior to screening is not available, participants may be included if HBsAg positive and negative for immunoglobulin M (IgM) antibodies to HBV core antigen at screening. 4. Participants who are not currently treated (defined as not having been on treatment with HBV antiviral medicines, including NAs and IFN products within 6 months prior to screening), including treatment-naïve participants (defined as never having received treatment with HBV antiviral medicines, including NAs and IFN products) should have: a. Serum HBV DNA at screening =2,000 IU /mL for HBeAg-negative participants and =20,000 IU/mL for HBeAg-positive participants, AND b. ALT levels at screening ULN on two sequential measurements at least 3 months apart (one of which is at screening). 5. Virologically suppressed participants should: a. be on stable HBV treatment, defined as currently receiving NA treatment (ETV, TDF, or TAF) for at least 6 months prior to screening and having been on the same NA treatment regimen (at the same dose) as used in this study (see Protocol Section 6.1) for at least 3 months at the time of screening, AND b. have serum HBV DNA 100 IU/mL at screening. 7. Participants must have a BMI (weight in kg divided by the square of height in meters) between 18.0 and 35 kg/m2, extremes included. 8. Participants must have: a. Fibroscan liver stiffness measurement =9.0 kPa within 6 months prior to screening or at the time of screening, OR b. If a fibroscan result is not available: a liver biopsy result classified as Metavir F0-F2 within 1 year prior to screening or at the time of screening. Note: Other radiologic liver staging modalities (eg, acoustic radiation force impulse) might be used if standard practice at the site or if otherwise validated and agreed with the sponsor. Results should be equivalent to Metavir F0-F2. Note: Conventional imaging procedures (eg, conventional liver ultrasound, computed tomography [CT] or magnetic resonance imaging [MRI]) and serum marker panels are not allowed to rule out severe fibrosis or cirrhosis. 9. Participants must sign an ICF indicating tha
Exclusion criteria
Exclusion criteria: 1. Participants with evidence of hepatitis A virus infection (hepatitis A antibody IgM), HCV infection (HCV antibody [participants with undetectable HCV RNA and documentation of sustained virological response at least 24 weeks after completion of HCV treatment might be enrolled after discussion with the sponsor]), HDV infection (HDV antibody), or hepatitis E virus infection (hepatitis E antibody IgM), or HIV-1 or HIV-2 infection (confirmed by antibodies) at screening. 2. Participants with any of the following laboratory abnormalities within 12 months prior to screening: a. Total bilirubin >1.5x ULN, b. Direct bilirubin >1.2x ULN, c. Prothrombin time >1.3x ULN, d. Serum albumin 100 ng/mL, g. Any other laboratory abnormality considered to be clinically significant by the investigator. 7. Participants with hemoglobin A1c >8% at screening. 8. Participants with a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence). 9. Participants with abnormal sinus rhythm (heart rate 100 beats per minute [bpm]); QT interval corrected for heart rate according to Fridericia (QTcF) >450 ms for male participants and >470 ms for female participants; QRS =120 ms; PR interval >220 ms; abnormal conduction; or any other clinically significant abnormalities on a 12-lead ECG at screening. 10. Participants with a history of or current cardiac arrhythmias (eg, tachycardia at rest), history of risk factors for Torsade de Pointes syndrome (eg, hypokalemia, family history of long QT Syndrome) or history or other clinical evidence of significant or unstable cardiac disease (eg, angina, congestive heart failure, myocardial infarction, diastolic dysfunction, significant arrhythmia, coronary heart diseas
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish the dose-response relationship for antiviral activity of 3 doses of JNJ-3989+NA and to evaluate the efficacy of combination regimens of JNJ-3989+NA (with and without JNJ-6379) and of JNJ-6379+NA.;Secondary Objective: 1. To evaluate the safety and tolerability of the study intervention throughout the study. 2. To evaluate the efficacy of the study intervention during follow-up phase. 3. To evaluate efficacy as measured by blood markers (such as HBsAg, HBeAg, HBV DNA, and ALT) during study intervention and follow-up. 4. To evaluate the frequency of virologic breakthrough. 5. To evaluate the efficacy of NA re-treatment in participants who meet the criteria for NA re-treatment. 6. To evaluate the PK of JNJ-3989, JNJ-6379, and NA, as applicable.;Primary end point(s): Proportion of participants meeting the NA treatment completion criteria at Week 48.;Timepoint(s) of evaluation of this end point: Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Proportion of participants with (S)AEs and abnormalities in clinical laboratory tests (including hematology, blood biochemistry, blood coagulation, and urinalysis, urine chemistry, and renal biomarkers), 12-lead ECGs, and vital signs. 2a. Proportion of participants with HBsAg seroclearance 24 weeks after completion of all study intervention at Week 48. 2b. Proportion of participants with HBsAg seroclearance 48 weeks after completion of all study intervention at Week 48. 2c. Proportion of participants with HBsAg seroclearance 24 weeks and 48 weeks after completion of all study intervention at any time during follow-up. 2d. Proportion of participants with HBV DNA 1 log10 IU/mL reduction in HBsAg from baseline). 3f. Proportion of HBeAg-positive participants with HBeAg* levels and/or changes from baseline below/above different cut-offs. 3g. Proportion of participants with HBV DNA levels and/or changes from baseline below/above different cut-offs (eg, <LLOQ of the assay). 3h. Proportion of participants with ALT decrease and normalization. 3i. Proportion of participants meeting the NA treatment completion criteria during follow-up. 4. Proportion of participants with virologic breakthrough. 5. Proportion of participants who reach HBV DNA undetectability after re-start of NA treatment during follow-up. 6. PK parameters of JNJ-3989, JNJ-6379, and NA, as applicable.;Timepoint(s) of evaluation of this end point: Throughout the duration of the study | — |
Countries
Belgium, Brazil, Canada, China, Czech Republic, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Malaysia, Poland, Russian Federation, Spain, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Operations Spain
JANSSEN CILAG, S.A.
Outcome results
None listed