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 UC
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 =65 years of age. M02. Participant 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. M03/A02. 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 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, or should be documented by absence of marker for acute infection such as positive immunoglobulin M (IgM) anti-hepatitis B surface (HBs) and anti-HBc antibodies, which can be tested at screening. The participants should be virologically suppressed. They should: o Be HBeAg-negative, o Be on stable HBV treatment, defined as currently receiving NA treatment (ETV, TDF, or TAF) for at least 24 months prior to screening and having been on the same NA treatment regimen (at the same dose) as used in this study (see Section 6.1) for at least 3 months at the time of screening, AND o Have serum HBV DNA <60 IU/mL on 2 sequential measurements at least 6 months apart (one of which is at screening), AND o Have documented ALT values <2.0x ULN on 2 sequential measurements at least 6 months apart (one of which is at screening). M04. 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. M05/A03. Participant must sign a Master ICF (specific for the Master Protocol PLATFORMPAHPB2001) and an ICF specific for this ISA indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study. M06. Participant 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/A04. Female participants must be (as defined in Attachment 5 of the Master Protocol PLATFORMPAHPB2001): 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) and must agree 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 Attachment 5 of the Master Protocol PLATFORMPAHPB2001. 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 (Section 5.3, Lifestyle Considerations) and is likely to complete the study as planned in this ISA (inc
Exclusion criteria
Exclusion criteria: M01/A01. Participants with evidence of hepatitis A virus infection (hepatitis A antibody IgM), hepatitis C virus (HCV) infection (HCV antibody and detectable HCV RNA), hepatitis D virus (HDV) infection (HDV antibody), hepatitis E virus infection (hepatitis E antibody IgM), or HIV 1 or HIV-2 infection (confirmed by antibodies) at screening. M02. Participants with evidence of hepatic decompensation at any time point prior to or at the time of screening: a. Direct bilirubin >1.2xULN (unless there is documentation of a benign cause such as Gilbert’s disease), OR b. Prothrombin time >1.3xULN (unless caused by anticoagulation therapy or vitamin K deficiency), OR c. Serum albumin 100 ng/mL; f. Any other laboratory abnormality considered to be clinically significant by the investigator (also see inclusion criterion M03/A02). 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. 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 >200 ms; abnormal conduction; or any other clinically significant abnormalities on a 12-lead ECG at screenin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of 48-week study intervention with JNJ-3989+JNJ-6379+NA regimen compared to NA alone.;Primary end point(s): Proportion of participants with HBsAg seroclearance at Week 72 (ie, 24 weeks after completion of all study interventions at Week 48) without restarting NA treatment.;Timepoint(s) of evaluation of this end point: Week 72;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 at the end of treatment. 3. To evaluate the efficacy as measured by blood markers (such as HBsAg, HBV DNA, and ALT) during study intervention and follow-up. 4. To evaluate the frequency of virologic breakthrough during study intervention. 5. To evaluate the proportion of participants requiring NA re-treatment during follow-up. 6. To identify baseline and on-treatment markers associated with sustained off-treatment response. 7. To evaluate the PK of JNJ 3989 (JNJ-3976 and JNJ-3924), JNJ-6379, and NA, as applicable. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Throughout the duration of the study;Secondary end point(s): 1. Safety and tolerability including but not limited to the 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. 2a. Proportion of participants with HBsAg seroclearance at Week 48. 2b. Proportion of participants with HBV DNA 1 log10 IU/mL reduction in HBsAg from baseline). 3i. Proportion of participants with HBV DNA levels and/or changes from baseline below/above different cut-offs (eg, <LLOQ of the assay). 3j. Proportion of participants with flares (virologic, biochemical, and clinical). 4. Proportion of participants with virologic breakthrough. 5. Proportion of participants who meet the NA re-treatment criteria. 6. Correlation of baseline characteristics and baseline/on-treatment viral blood markers (such as baseline NA treatment duration, age, and baseline/on-treatment HBsAg levels) with selected off-treatment efficacy variables. 7. Population PK parameters of JNJ-3989 (JNJ-3976 and JNJ-3924), JNJ-6379, and NA, as applicable. | — |
Countries
Belgium, France, Germany, Italy, Poland, Spain, United Kingdom
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International N.V.
Outcome results
None listed