A Clinical Study to Investigate the Efficacy and Safety of JNJ-73763989+JNJ-56136379+Nucleos(t)ide Analog (NA) Regimen Compared to NA Alone for the Treatment of Chronic Hepatitis B Virus Infectio
- Conditions
- Chronic Hepatitis B Virus InfectionMedDRA version: 20.1 Level: PT Classification code 10008910 Term: Chronic hepatitis B System Organ Class: 10021881 - Infections and infestationsTherapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2019-002674-31-ES
- Lead Sponsor
- Janssen Sciences Ireland UC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 120
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.
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 <3.2 g/dL, OR
d. History of clinical symptoms of hepatic decompensation (eg, ascites, jaundice, hepatic encephalopathy or coagulopathy, especially if resulting in a Child Pugh classification B or C at the time clinical symptoms present or at screening).
M03. History or evidence of clinical signs or symptoms of hepatic decompensation, including but not limited to: portal hypertension, ascites, hepatic encephalopathy, esophageal varices.
M04. Participants with evidence of liver disease of non-HBV etiology. This includes but is not limited to hepatitis infections mentioned in exclusion criterion M01/A01, drug- or alcohol related liver disease, autoimmune hepatitis, hemochromatosis, Wilson’s disease, a 1 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing cholangitis, Gilbert’s syndrome (mild cases are allowed, see exclusion criterion M02a) or any other non-HBV liver disease considered clinically significant by the investigator.
M05/A02. Participants with history or signs of cirrhosis or portal hypertension (nodules, no smooth liver contour, no normal portal vein, spleen size =12 cm) or signs of HCC on an abdominal ultrasound performed within 6 months prior to screening or at the time of screening. In case of suspicious findings on conventional ultrasound the participant may still be eligible if HCC has been ruled out by a more specific imaging procedure (contrast enhanced ultrasound, CT or MRI).
M06/A03. Participants with one or more of the following laboratory abnormalities at screening as defined by the Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grading Scale (see Section 10.9, Appendix 9, DAIDS Table):
a. Estimated creatinine clearance =grade 3 (<60 mL/min) at screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula;
b. Pancreatic lipase elevation =grade 3;
c. Hemoglobin =10.9 g/dL (males), =10.4 g/dL (females);
d. Platelet count =lower limit of normal (LLN);
e. Alpha-fetoprotein >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 <45
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method