A clinical study to evaluate efficacy, pharmacokinetics, safety, and tolerability of treatment with JNJ-73763989, pegylated interferon alpha- 2a, nucleos(t)ide analog with or without JNJ-56136379 in treatment-naïve patients with HBeAg positive chronic hepatitis B virus infection.
- 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
- EUCTR2019-004978-26-DE
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 80
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 <9 months of NA treatment =12 months prior to screening) including treatment-naïve participants (defined as never having received treatment with HBV antiviral medicines, including NAs and IFN products), AND
b. be HBeAg positive, AND
c. have serum HBV DNA at screening =20,000 IU/mL, AND
d. have ALT <2x ULN at screening and at least once >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
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 <3.2 g/dL, OR
e. 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 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 M02.1) or any other non-HBV liver disease considered clinically significant by the investigator.
M05 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 have been ruled out by a more specific imaging procedure (contrast enhanced ultrasound, CT or MRI).
M06/A06 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:
a. Estimated glomerular filtration rate based on serum creatinine (eGFRcr) <80 mL/min/1.73 m^2 at screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula;
b. Pancreatic lipase elevation =grade 3;
c. Pancreatic amylase 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 >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 <45 or >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
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