A Clinical Study to Investigate the Efficacy and Safety of Different Combination Regimens Including JNJ-73763989 and/or JNJ-56136379 for the Treatment of Chronic Hepatitis B Virus Infectio
- Conditions
- Chronic Hepatitis B Virus InfectionMedDRA version: 20.1Level: PTClassification code 10008910Term: Chronic hepatitis BSystem Organ Class: 10021881 - Infections and infestationsTherapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2019-000622-22-IT
- Lead Sponsor
- Janssen Sciences Ireland Unlimited Company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 450
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 <10x ULN AND >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 <60 IU/mL on two sequential measurements at least 6 months apart (one of which is atscreening), AND
c. have ALT values =2x ULN on two sequential measurements at least 6 months apart (one of which is at screening).
6. Participants must have HBsAg >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.
Please refer to the protocol for a complete list
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 or at the time of screening:
a. Total bilirubin >1.5x ULN,
b. Direct bilirubin >1.2x ULN,
c. Prothrombin time >1.5x ULN,
d. Serum albumin <3.0 g/dL.
3. History or evidence of clinical signs/symptoms of hepatic decompensation including but not limited to: portal hypertension, ascites, hepatic encephalopathy, esophageal varices.
4. Participants with evidence of liver disease of non-HBV etiology. This includes but is not limited to hepatitis virus infections mentioned in exclusion criterion 1, 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 2a), or any other non-HBV liver disease considered clinically significant by the investigator.
5. Participants with signs of HCC or clinically relevant renal abnormalities 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 or clinically relevant renal abnormalities has been ruled out by a more specific imaging procedure (contrast enhanced ultrasound, CT or MRI).
6. 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 Protocol Section 10.8, Appendix 8, DAIDS Table):
a. Estimated glomerular filtration rate (eGFR) =grade 3 (i.e. <60ml/min/1.73 m2) at screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula,
b. Pancreatic amylase =grade 3,
c. Lipase elevation =grade 3,
d. Hemoglobin =10.9 g/dL (males), =10.4 g/dL (females),
e. Platelet count =lower limit of normal (LLN),
f. Alpha-fetoprotein (AFP) >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).
Please refer to the protocol for a full list of the exclusion criteria
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