Hepatitis B, Chronic

The purpose of this study is to evaluate the efficacy of the study intervention based on hepatitis B surface antigen (HBsAg) levels.

JNJ-73763989
JNJ-64300535

JNJ-73763989
JNJ-64300535

vial
vial

200 mg/ml
6 mg/ml

Percentage of Participants with a Reduction of at Least 2 log10 International Units per Milliliter (IU/mL) in Hepatitis B Surface Antigen (HBsAg) Levels from Baseline to Week 36 [ Time Frame: Baseline to Week 36 (end of study intervention) ]
Percentage of participants with a reduction of at least 2 log10 IU/mL in HBsAg levels from baseline to Week 36 will be reported.

1. Male or female participants ≥18 years of age (or the legal age of consent in the jurisdiction in
which the study is taking place).
2. 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.
3. Criterion modified per Amendment 2.
3.1 Criterion modified per Amendment 3.3.2 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 absence of marker for acute infection such as positive IgM anti-HBs
and anti-HBc antibodies.
Note: Participants with ALT levels within normal range can be allowed, provided they fulfill
the criteria defined for inactive carriers or immune tolerant participants in ISAs that target
these patient populations (refer to inclusion criteria 3c and 3d, respectively, below).
The targeted chronic HBV-infected population will be defined in each specific ISA and may
include (but is not limited to) one or more of the different patient groups described below:
a. Participants who are not currently treated (defined as not having been on HBV
treatment, including NAs and IFN products within 6 months prior to screening), including
treatment-naïve participants (defined as never having received HBV treatment, including
NAs and IFN products) should have:
o Serum HBV DNA at screening 2,000 IU/mL for HBeAg-negative participants and
≥20000 IU/mL for HBeAg-positive participants, AND
o ALT levels at screening <10xULN and >ULN on 2 sequential measurements at least
3 months apart (one of which is at screening). Historical data should be collected in
the case report form (CRF).
b. Virologically suppressed participants should:
o be on stable HBV treatment, defined as currently receiving NA treatment 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 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 <2.0xULN on 2 sequential measurements at least
6 months apart (one of which is at screening)
c. Inactive carriersa
should:
o be 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), AND
o be HBeAg-negative, AND
o have serum HBV DNA <2,000 IU /mL, AND
o have normal ALT at screening and at least once >12 months prior to screening.
d. Immune tolerantb participants should:
o be treatment-naïve participants (defined as never having received treatment with
HBV antiviral medicines, including NAs and IFN products), AND
o be HBeAg positive, AND
o have serum HBV DNA at screening ≥20,000 IU/mL, AND
o have normal ALT at screening and at least once >6 months prior to screening.
e. HBV/HDV co-infected participants should:
o have a chronic HDV infection documented by HDV RNA at screening. In addition,
chronicity must be documented by positive HDV antibodies or HDV RNA at least 6
months prior to screening.
4. 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.
5. Participant must sign a Master ICF (specific for this Master protocol) indicating that he or she
understands the purpose of, and procedures required for, the study and is willing to participate
in the study.
6. 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.
7. Female participants must be (as defined in Attachment 5)
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 agrees to remain on a highly effective method while receiving study
intervention and until the end of relevant systemic exposure as specified in each ISA.
Examples of highly effective methods of contraception are provided in Attachment 5.
. Female participants of childbearing potential must have a negative highly sensitive serum
pregnancy test (-human chorionic gonadotropin [-hCG]) at screening and a negative urine
pregnancy test on Day 1 before the first dose of study intervention.
9. In the investigator’s opinion, the participant is able to understand and comply with protocol
requirements, instructions, and study restrictions (Section 5.3) and is likely to complete the
study as planned per ISA (including the procedures outlined in the Master protocol).
10. Male participants must agree to follow contraceptive requirements as specified in each ISA

Criterion modified per Amendment 2.
1.1 Participants with evidence of hepatitis A virus infection (hepatitis A antibody IgM), HCV
infection (HCV antibody), or hepatitis E virus (HEV) infection (hepatitis E antibody IgM), or
HIV-1 or HIV-2 infection (confirmed by antibodies) at screening.
Note:
o Participants with a positive HCV antibody test can be enrolled if they have negative
HCV RNA at screening and documented negative HCV RNA at least 6 months prior
to screening.
o Participants with a positive HDV antibody test may be enrolled after discussion with
the sponsor if an active HDV co-infection can be ruled out by documentation of
negative HDV RNA.a
o Participants with a positive IgM antibody test for HEV infection may be enrolled
after discussion with the sponsor if an active HEV infection can be ruled out by
documentation of negative anti-HEV IgG.b
Criterion modified per Amendment 2:
2.1 Participants with evidence of hepatic decompensation at any time point prior to or at the
time of screening:
a. Total bilirubin >1.5x ULNa
b. direct bilirubin >1.2xULNa
, OR
c. prothrombin time >1.3xULNa
(unless caused by anticoagulation therapy or vitamin K
deficiency), OR
d. serum albumin <3.2 g/dLa
, 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).
3. History or evidence of clinical signs or 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 infections mentioned in exclusion criterion 1, drug- or alcohol-related liver
disease, autoimmune hepatitis, hemochromatosis, Wilson’s disease, α-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. Criterion modified per Amendment 2:
5.1 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, computed tomography [CT] or magnetic resonance
imaging [MRI]).
6. Criterion modified per Amendment 2:
6.1 Participants with one or more of the following laboratory abnormalities at screening as
defined by the Division of AIDS (DAIDS) Toxicity Grading Scale3
:
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. 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 (also see inclusion criterion 3).
Note: Retesting of abnormal laboratory values that may lead to exclusion will be allowed
once without prior approval from the sponsor. Retesting will take place at an unscheduled
visit during the screening phase. Participants with a normal value at retest may be included.
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 are considered cured with minimal risk of recurrence).
9. Criterion modified per Amendment 2:
9.1 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.
Note: Retesting of an abnormal ECG that may lead to exclusion will be allowed once without
prior asking approval from the sponsor. Retesting will take place during an unscheduled visit
in the screening phase. Participants not meeting the above exclusion criterion at retest may be
included.
10. Participants with a history of or current cardiac arrhythmias (eg, extrasystole, tachycardia at
rest), history of risk factors for Torsade de Pointes syndrome (eg, hypokalemia, family history
of long QT Syndrome) or history or other clinical evidence of significant or unstable cardiac
disease (eg, angina, congestive heart failure, myocardial infarction, diastolic dysfunction,
significant arrhythmia and/or coronary heart disease), moderate to severe valvular disease, or
uncontrolled hypertension at screening.
11. Participants with any current or previous illness for which, in the opinion of the investigator
and/or sponsor, participation would not be in the best interest of the participant
(eg, compromise the well-being) or that could prevent, limit, or confound the
protocol-specified assessments. This may include but is not limited to significant vascular,
pulmonary (eg, chronic obstructive pulmonary disease), gastrointestinal (eg, significant
diarrhea, gastric stasis, or constipation that in the investigator’s opinion could influence drug
absorption or bioavailability), endocrine (eg, thyroid disease), neurologic, hematologic,
rheumatologic, psychiatric, neoplastic, or metabolic disturbances. Any condition possibly
affecting drug absorption (eg, gastrectomy or other significant gastrointestinal tract surgery,
such as gastroenterostomy, small bowel resection, or active enterostomy) will also lead to
exclusion.
12. Participants who have received an organ transplant (except for skin, hair, or cornea
transplants).
13. Participants with any history of or current clinically significant skin disease requiring regular
or periodic treatment.
14. Participants with clinically-relevant alcohol or drug abuse within 12 months of screening.
15. Participants with history of clinically relevant drug rash.
16. Participants who have taken any disallowed therapies as noted in Section 6.5 before screening.
17. Participants having used any invasive investigational medical device within 3 months, or
having received an investigational intervention or a biological product, immunoglobulin or
other blood product not intended for the treatment of HBV within 6 months or 5 half-lives
(whichever is longer), before the planned first dose of study intervention, or is currently
enrolled in an interventional clinical study with an investigational product.
18. Female participants who are pregnant, or breast-feeding, or planning to become pregnant
while enrolled in this study and before the end of relevant systemic exposure as specified in
each ISA.
19. Male participants who plan to father a child while enrolled in this study and before the end of
relevant systemic exposure as specified in each ISA.
20. Participants who had major surgery (eg, requiring general anesthesia), excluding diagnostic
surgery, within 12 weeks before screening; or will not have fully recovered from surgery; or
has surgery planned during the time of expected participation in the study.
Note: Participants with planned surgical procedures to be conducted under local anesthesia
may participate.
21. Participant is an employee of the investigator or study site, with direct involvement in the
proposed study or other studies under the direction of that investigator or study site, as well
as family members of the employees or the investigator.
22. Criterion modified per Amendment 2:
22.1 Vulnerable participants (eg, incarcerated individuals, individuals under a legal protection
measure).