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-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: M01/A01 Male or female participants =18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) to =55 years of age with a maximum of approximately 10 participants >45 to = 55 years of age. M02 Participants must be medically stable based on 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. M03d/A03 Participants must have chronic HBeAg positive 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, documented transmission event. If none of the above are available, the following ways of documenting chronicity are acceptable at time of screening: liver biopsy with changes consistent with chronic HBV, or absence of marker for acute infection such as positive immunoglobulin M (IgM) antihepatitis B surface (HBs) and anti-HBc antibodies. In addition, participants must: a. be not currently treated (defined as having received 6 months prior to screening. M04 Participants must have a body mass index (BMI; weight in kg divided by the square of height in meters) between 18.0 and 35.0 kg/m2, extremes included. M05/A05 Participants (or their legally acceptable representative) must sign a Master ICF (specific for the Master Protocol PLATFORMPAHPB2001) and must sign an ICF specific for this intervention cohort, indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study. M06 Participants must sign a separate ICF if he or she agrees to provide an optional DNA sample for research (where local regulations permit). Refusal to give consent for the optional DNA research sample does not exclude a participant from participation in the study. M07/A07 Female participants must be: a. Not of childbearing potential, OR 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 provided in Section 10.8 Appendix 8 of Protocol. M08 Female participants of childbearing potential must have a negative highly sensitive serum pregnancy test at screening and a negative urine pregnancy test on Day 1 before the first dose of study intervention. M09 In the investigator’s opinion, the participant is able to understand and comply with protocol requirements, instructions, and study restrictions and is likely to complete the study as planned per ISA (including the procedures outlined in the Master protocol PLATFORMPAHPB2001). M10/A1
Exclusion criteria
Exclusion criteria: M01/A01 Participants with evidence of hepatitis A virus infection (hepatitis A antibody IgM), HCV infection (HCV antibody), hepatitis D virus (HDV) infection (HDV antibody), hepatitis E virus (HEV) infection (hepatitis E antibody IgM), or HIV-1 or HIV 2 infection (laboratory confirmed) at screening. M02.1 Participants with evidence of hepatic decompensation at any time point prior to or at the time of screening: a. Total bilirubin >1.5xULN, OR b. Direct bilirubin >1.2xULN, OR c. Prothrombin time >1.3xULN (unless caused by anticoagulation therapy or vitamin K deficiency), OR d. Serum albumin 100 ng/mL; g. Any other laboratory abnormality considered to be clinically significant by the investigator. M07 Participants with hemoglobin A1c >8% at screening. M08 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 are considered cured with minimal risk of recurrence). M09.1 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. M10 Participants with a history of or current cardiac arrhythmias (eg, extrasystole, tachycardia at rest), history of risk
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of a treatment regimen of JNJ-3989 + PegIFN-a2a + NA.;Secondary Objective: 1. To evaluate the safety and tolerability of the study intervention. 2. To evaluate the efficacy of the study intervention during the treatment period. 3. To evaluate the efficacy of the study intervention during the follow-up (FU) phase. 4. To evaluate efficacy of the study intervention as measured by blood markers (such as HBsAg, HBeAg, HBV DNA, and alanine aminotransferase [ALT]) during study intervention and follow-up. 5. To evaluate the frequency of virologic breakthrough. 6. To evaluate the efficacy of NA re-treatment in participants who meet the criteria for NA re treatment. 7. To evaluate the pharmacokinetics (PK) of JNJ 3989 and optionally of JNJ-6379, NA and/or PegIFN a2a. ;Primary end point(s): Proportion of participants with HBsAg seroclearance 24 weeks after stopping all study interventions of the consolidation phase and without restarting NA treatment;Timepoint(s) of evaluation of this end point: 24 weeks after stopping all study interventions of the consolidation phase and without restarting NA treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Safety and tolerability including but not limited to the proportion of participants with (serious) adverse events (S)AEs and abnormalities in clinical laboratory tests (including hematology, blood biochemistry, blood coagulation, urinalysis, urine chemistry, and renal biomarkers), 12 lead electrocardiograms (ECGs), vital signs, and physical examinations throughout the study. 2a. Proportion of participants reaching HBsAg <10 IU/mL at the end of the induction phase (Week 36). 2b. Time to reach HBsAg <10 IU/mL. 2c. Proportion of participants meeting the NA treatment completion criteria at the end of the consolidation phase. 3a. Proportion of participants with HBsAg seroclearance 48 weeks after stopping all study interventions of the consolidation phase and without restarting NA treatment. 3b. Proportion of participants with HBV DNA <LLOQ 48 weeks after stopping all study interventions of the consolidation phase and without restarting NA treatment. 3c. Frequency of viral and/or biochemical flares and/or clinical flares. 3d. Proportion of participants requiring NA re-treatment. 4a. Proportion of participants with (sustained) reduction, suppression, and/or seroclearance considering single and multiple markers (such as HBsAg, HBeAg, HBV DNA, and ALT). 4b. Proportion of participants with HBsAg and HBeAg seroconversion. 4c. Change from baseline over time in HBsAg, HBeAg, and HBV DNA. 4d. Time to achieve HBsAg seroclearance, HBeAg seroclearance, and/or HBV DNA <LLOQ. 4e. Proportion of participants with HBeAg, HBsAg, and HBV DNA levels and/or changes from baseline below/above different cut-offs. 5. Proportion of participants with virologic breakthrough. 6. Proportion of participants who reach HBV DNA undetectability after re-start of NA treatment during follow-up. 7a. PK parameters of JNJ-3989. 7b. Optionally, PK parameters of JNJ-6379, NA and/or PegIFN a2a compared to historical data.;Timepoint(s) of evaluation of this end poin | — |
Countries
Belgium, Canada, Czechia, France, Germany, Japan, Poland, Russian Federation, Spain, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International N.V.
Outcome results
None listed