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
Sponsors
Janssen Sciences Ireland Unlimited Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult participants =18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) to =65 years of age. 2. Participants must be medically stable on the basis of physical examination, medical history, vital signs, and triplicate 12-lead ECG performed at screening. Any abnormalities must be consistent with the underlying illness in the study population and this determination must be recorded in the participant's source documents and initialed by the investigator. 3. Participants must have HBV infection documented by serum HBsAg positivity at screening. In addition, chronicity must be documented by any of the following at least 6 months prior to screening: serum HBsAg positivity, HBeAg positivity or HBV DNA positivity, ALT elevation above ULN without another cause than HBV infection, documented transmission event, liver biopsy with changes consistent with chronic HBV. If none of the above are available, the following ways of documenting chronicity are acceptable at the time of screening: absence of marker for acute infection such as immunoglobulin M (IgM) anti-HBs and anti-HBc antibodies, which can be tested at screening. 4. Participants who are not currently treated (defined as not having been on HBV treatment, including NAs and IFN products within 6 months prior to screening), including treatment-naïve participants (defined as never having received HBV treatment, including NAs and IFN products) should: a. be HBeAg positive, AND b. have serum HBV DNA at screening =20,000 IU /mL, AND c. have ALT levels at screening 100 IU/mL at screening. 7. Participants must have a body mass index (weight in kg divided by the square of height in meters) between 18.0 and 35.0 kg/m2, extremes included. 8. Participants must have fibroscan liver stiffness measurement =9.0 kPa within 6 months prior to screening or at the time of screening. 9.Female participants of childbearing potential must have a negative highly sensitive serum pregnancy test (B-human chorionic gonadotropin [B-hCG]) at screening and a negative urine pregnancy test on Day 1 before the first dose of study intervention. 10. A woman must be (as defined in Section 10.8, Appendix 8, Contraceptive and Barrier Guidance and Collection of Pregnancy Information): a. not of childbearing potential b. of childbearing potential and practicing a highly effective, preferably user-independent method of contraception (failure rate of <1% per year when used consistently and correctly) for at least 30 days prior to screening and agrees to remain on a highly effective method while receiving study intervention and until 90 days after last dose of study intervention. Examples of highly effective methods of contraception are located in Section 10.8, Appendix 8, Contraceptive
Exclusion criteria
Exclusion criteria: 1. Participants with evidence of hepatitis A virus infection (hepatitis A antibody IgM), HCV infection (HCV antibody), hepatitis D virus (HDV) infection (HDV antibody), or hepatitis E virus (HEV) infection (HEV antibody IgM), or HIV-1 or HIV-2 infection (laboratory confirmed) at screening. 2. Participants with any of the following laboratory abnormalities within 12 months prior to screening or at the time of screening: a. Total bilirubin >1.5x ULN, OR b. Direct bilirubin >1.2x ULN, OR c. Serum albumin 100 ng/mL; g. Any other laboratory abnormality considered to be clinically significant by the investigator. 7. Participants with presence of coagulopathy or bleeding disorder as indicated by: a. International normalized ratio (INR) =1.1 x ULN; b. Partial thromboplastin time > 1.1 x ULN; c. Any signs of prolonged bleeding (>10 minutes). 8. Participants with presence of hemoglobinopathy (including sickle cell disease, thalassemia). 9. Participants who had a liver biopsy performed prior to screening that led to complications and that in the opinion of the investigator would prohibit another liver biopsy. 10. Participants with history of amyloidosis. 11. Participant refusal to accept blood transfusions. 12. Participants with hemoglobin A1c >8% at screening. 13. Participants with a history of malignancy within 5 years prior to screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which are considered cured with minimal risk of recurrence). 14. Participants with abnormal sinus rhythm (heart rate 100 beats per minute [bpm]); QT interval corrected for heart rate according to Fridericia’s formula (QTcF) >450 ms for males and >470 ms for females; QRS interval =120 ms; PR interval >220 ms ; abnormal conduction; or any other clinically significant abnormalities on a 12-lead ECG at screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess changes in intrahepatic HBsAg between baseline and on-treatment liver biopsy in response to JNJ-3989-based combination treatment;Secondary Objective: 1. To assess changes in intrahepatic immune response between baseline and on-treatment liver biopsy. 2. To assess changes in intrahepatic viral nucleic acids and proteins between baseline and on-treatment liver biopsy. 3. To evaluate the efficacy of the study intervention as measured in blood. 4. To evaluate the frequency of virologic breakthrough during study intervention. 5. To assess HBV-specific T-cell responses. 6. To evaluate the safety and tolerability of the study intervention. 7. To evaluate the plasma PK of JNJ-3989, and optionally of JNJ-6379, NA and PegIFN-a2a, as applicable.;Primary end point(s): Changes in the proportion of HBsAg positive hepatocytes between baseline and on-treatment Week 40.;Timepoint(s) of evaluation of this end point: Week 40 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Changes between baseline and on-treatment liver biopsy in intrahepatic immune response (eg, CD45+ T-cells, CD4+ T-cells, CD8+ T-cells, Natural Killer cells, and dendritic cells) in terms of proportion of cells, cell types, and spatial redistribution. 2a. Changes from baseline in intrahepatic viral parameters (such as cccDNA, pgRNA, intrahepatic RNA, or HBsAg in terms of copy number, or number of positive cells). 2b. Changes from baseline in intrahepatic cccDNA levels and transcriptional activity (pgRNA/cccDNA ratio). 3a. The proportion of participants during the study intervention and follow-up phases with: -HBsAg seroclearance at Week 72 (ie, 24 weeks after completion of all study interventions at Week 48) without restarting NA treatment. -(Sustained) Reduction, suppression, and/or seroclearance considering single and multiple markers (such as HBsAg, HBeAg, HBV DNA and ALT) -HBsAg and HBeAg seroconversion -Flares (virologic, biochemical, and clinical) 3b. Time to first HBsAg seroclearance 4. Proportion of participants with virologic breakthrough. 5. Changes from baseline in HBV-specific peripheral blood T-cell responses during the study intervention and follow-up phases. 6. Proportion of participants with (S)AEs and abnormalities in clinical laboratory tests (including hematology, blood biochemistry, blood coagulation, urinalysis, urine chemistry, and renal biomarkers), 12-lead ECGs, vital signs, and physical examinations throughout the study. 7. Plasma PK parameters of JNJ-3976, JNJ-3924, and optionally of JNJ-6379, NA and PegIFN-a2a, as applicable.;Timepoint(s) of evaluation of this end point: Throughout the study duration. | — |
Countries
Belgium, Canada, France, Germany, Italy, New Zealand, Poland, United Kingdom, United States
Contacts
Public ContactClnical Registry Group
Janssen-Cilag International NV
Outcome results
None listed