Clinical Trials List
Protocol Number73763989HPB2004
Completed
2020-10-01 - 2025-12-31
Phase II
Recruiting3
ICD-10B17.0
Acute delta-(super) infection of hepatitis B carrier
ICD-9070.52
Hepatitis delta without mention of active hepatitis B disease without mention of hepatic coma
A Phase 2, Multicenter, Randomized, Double-blind, Placebo‑controlled Study with Deferred Active Treatment to Investigate the Efficacy, Safety, and Pharmacokinetics of JNJ‑73763989 + Nucleos(t)ide Analog in Participants Co‑infected with Hepatitis B and Hepatitis D Virus
-
Trial Applicant
Johnson & Johnson
-
Sponsor
Johnson & Johnson
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Wei-Fan Hsu 未分科
- Hsueh-Chou Lai 未分科
- Hung-Yao Chen 未分科
- Tsung-Yu Tsai 未分科
- Hung-Wei Wang 未分科
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 梁博程 Division of General Internal Medicine
- Ming-Lun Yeh Division of General Internal Medicine
- Ming-Lung Yu Division of General Internal Medicine
- Chia-Yen Dai Division of General Internal Medicine
- Chung-Feng Huang Division of General Internal Medicine
- Jee-Fu Huang Division of General Internal Medicine
- 黃駿逸 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 楊宏志 未分科
- Chen-Hua Liu 未分科
- 曾岱宗 未分科
- Shih-Jer Hsu 未分科
- Chun-Jen Liu 未分科
- 蘇東弘 未分科
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Patients infected with both hepatitis B and D viruses
Objectives
To evaluate on-treatment efficacy against HDV of JNJ-3989 + NA regimen compared to NA alone.
Test Drug
JNJ-73763989
Active Ingredient
JNJ-73763989
Dosage Form
Injection
Dosage
200 mg/mL
Endpoints
Main outcome indicators: At 48 weeks, the percentage of participants whose HDV RNA decreased >= 2 log 10 IU/mL or HDV RNA TND combined with normal ALT compared to the baseline period.
Timeline: Week 48
Explanation: It will be provided that at the 48th week, the hepatitis D virus (HDV) ribonucleic acid (RNA) has decreased by more than or equal to (>=) 2 log10 international units/ml (IU/mL) from the baseline period, or HDV RNA has not been detected Percentage of participants (TND) combined with normal alanine transamidation (ALT).
Timeline: Week 48
Explanation: It will be provided that at the 48th week, the hepatitis D virus (HDV) ribonucleic acid (RNA) has decreased by more than or equal to (>=) 2 log10 international units/ml (IU/mL) from the baseline period, or HDV RNA has not been detected Percentage of participants (TND) combined with normal alanine transamidation (ALT).
Inclution Criteria
1. male or female (according to their reproductive organs and functions assigned by
chromosomal complement).
2. 18 (or the legal age of consent in the jurisdiction in which the study is taking place) to
65 years of age, inclusive.
3. medically stable on the basis of physical examination, medical history, vital signs, and
12-lead ECG performed at screening. Any abnormalities, must be consistent with the
underlying illness in the study population and this determination must be recorded in the
participant's source documents and initialed by the investigator.
4. must have:
chronic hepatitis B infection either HBeAg positive or HBeAg negative and
either receiving NA treatment or no NA treatment. 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)
chronic HDV infection documented by positive HDV antibodies or HDV RNA
at screening. In addition, chronicity must be documented by positive HDV
antibodies or HDV RNA at least 3 months prior to screening.
5. must have HDV RNA values at screening ≥1,000 IU/mL.
6. must have ALT levels <10x ULN at screening.
7. Participants must have a BMI (weight in kg divided by the square of height in meters)
between 18.0 and 35.0 kg/m2, extremes included.
8. must have presence or absence of compensated cirrhosis based on:
a. No cirrhosis: LSM <12.5 kPa by VCTE (FibroScan) within 6 months prior to
screening or at the time of screening or liver biopsy within 1 year prior to
screening, OR
b. Cirrhosis: LSM ≥12.5 kPa by VCTE (FibroScan) within 6 months prior to
screening or at the time of screening or liver biopsy within 1 year prior to
screening; and a Child-Pugh score A.
Note: If FibroScan is not available, other radiologic liver staging modalities
(eg, acoustic radiation force impulse) might be used at screening if standard practice at
the site or if otherwise validated and agreed with the sponsor.
Note: Conventional imaging procedures (eg, conventional liver ultrasound, computed
tomography [CT] or magnetic resonance imaging [MRI]) and serum marker panels are
not allowed.
9. must sign an ICF indicating that he or she understands the purpose of, and procedures
required for, the study and is willing to participate in the study.
10. 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.
11. a woman of childbearing potential must have a negative highly sensitive serum
(β-human chorionic gonadotropin [β-hCG]) at screening and a negative urine pregnancy
test on Day 1 before the first dose of study intervention.
12. a woman must be (as defined in Section 10.8, Appendix 8, Contraceptive and Barrier
Guidance)
a. Not of childbearing potential
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 - the end of relevant systemic exposure.
Examples of highly effective methods of contraception are located in Section 10.8,
Appendix 8, Contraceptive Guidance and Barrier Guidance.
13. a woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction during the study and for a period of 90 days after the last dose of study
intervention.
14. a male participant must wear a condom when engaging in any activity that allows for
passage of ejaculate to another person while receiving study intervention and until
90 days after the last dose of study intervention.
15. a male participant must agree not to donate sperm for the purpose of reproduction
during the study and for a minimum 90 days after receiving the last dose of study
intervention.
16. In the investigator’s opinion, the participant is able to understand and comply with
protocol requirements, instructions, and lifestyle
chromosomal complement).
2. 18 (or the legal age of consent in the jurisdiction in which the study is taking place) to
65 years of age, inclusive.
3. medically stable on the basis of physical examination, medical history, vital signs, and
12-lead ECG performed at screening. Any abnormalities, must be consistent with the
underlying illness in the study population and this determination must be recorded in the
participant's source documents and initialed by the investigator.
4. must have:
chronic hepatitis B infection either HBeAg positive or HBeAg negative and
either receiving NA treatment or no NA treatment. 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)
chronic HDV infection documented by positive HDV antibodies or HDV RNA
at screening. In addition, chronicity must be documented by positive HDV
antibodies or HDV RNA at least 3 months prior to screening.
5. must have HDV RNA values at screening ≥1,000 IU/mL.
6. must have ALT levels <10x ULN at screening.
7. Participants must have a BMI (weight in kg divided by the square of height in meters)
between 18.0 and 35.0 kg/m2, extremes included.
8. must have presence or absence of compensated cirrhosis based on:
a. No cirrhosis: LSM <12.5 kPa by VCTE (FibroScan) within 6 months prior to
screening or at the time of screening or liver biopsy within 1 year prior to
screening, OR
b. Cirrhosis: LSM ≥12.5 kPa by VCTE (FibroScan) within 6 months prior to
screening or at the time of screening or liver biopsy within 1 year prior to
screening; and a Child-Pugh score A.
Note: If FibroScan is not available, other radiologic liver staging modalities
(eg, acoustic radiation force impulse) might be used at screening if standard practice at
the site or if otherwise validated and agreed with the sponsor.
Note: Conventional imaging procedures (eg, conventional liver ultrasound, computed
tomography [CT] or magnetic resonance imaging [MRI]) and serum marker panels are
not allowed.
9. must sign an ICF indicating that he or she understands the purpose of, and procedures
required for, the study and is willing to participate in the study.
10. 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.
11. a woman of childbearing potential must have a negative highly sensitive serum
(β-human chorionic gonadotropin [β-hCG]) at screening and a negative urine pregnancy
test on Day 1 before the first dose of study intervention.
12. a woman must be (as defined in Section 10.8, Appendix 8, Contraceptive and Barrier
Guidance)
a. Not of childbearing potential
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 - the end of relevant systemic exposure.
Examples of highly effective methods of contraception are located in Section 10.8,
Appendix 8, Contraceptive Guidance and Barrier Guidance.
13. a woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction during the study and for a period of 90 days after the last dose of study
intervention.
14. a male participant must wear a condom when engaging in any activity that allows for
passage of ejaculate to another person while receiving study intervention and until
90 days after the last dose of study intervention.
15. a male participant must agree not to donate sperm for the purpose of reproduction
during the study and for a minimum 90 days after receiving the last dose of study
intervention.
16. In the investigator’s opinion, the participant is able to understand and comply with
protocol requirements, instructions, and lifestyle
Exclusion Criteria
2. Main exclusion criteria:
1. Participants with evidence of hepatitis A virus infection (hepatitis A antibody
immunoglobulin M [IgM]), hepatitis C virus (HCV) infection (HCV antibody), or
hepatitis E virus (HEV) infection (hepatitis E antibody IgM), or human
immunodeficiency virus type 1 (HIV-1) or HIV type 2 (HIV-2) infection (confirmed
by antibodies) at screening.
Note:
− 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.
− 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.
2. any of the following laboratory abnormalities within 12 months prior to screening or
at time of screening:
a. Total bilirubin >1.7x ULN,
b. Direct bilirubin >1.4x ULN,
c. Prothrombin time >1.3x ULN,
d. Serum albumin <3.2 g/dL.
3. history or evidence of clinical signs/symptoms of hepatic decompensation including but not limited to: portal hypertension, ascites, hepatic encephalopathy.
Note: Participants with uncomplicated splenomegaly may be enrolled after
consultation with the sponsor.
4. Child-Pugh score >6.
5. evidence of liver disease of non-HDV or 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,
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/HDV or non-viral liver disease considered clinically significant by the
investigator.
6. 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).
7. 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 (eGFR) ≥grade 3 (ie, <60 mL/min/1.73 m2)
at screening, calculated by the Chronic Kidney Disease Epidemiology
Collaboration (CKD-EPI) formula,
b. Total amylase ≥grade 3,
c. Lipase elevation ≥grade 3,
d. Hemoglobin ≤10.9 g/dL (males), ≤10.4 g/dL (females),
e. Platelet count ≤100,000/dL,
f. Alpha-fetoprotein (AFP) >100 ng/mL,
g. Any other laboratory abnormality considered to be clinically significant by the
investigator.
Note: Participants with AFP >ULN (but ≤100 ng/mL) may be eligible if HCC can be
ruled out based on a sensitive imaging study (eg, enhanced ultrasound, CT, or MRI)
during screening.
8. hemoglobin A1c >8% at screening.
9. 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).
10. abnormal sinus rhythm (heart rate <45 or >100 beats per minute [bpm]); QT interval
corrected for heart rate according to Fridericia (QTcF) >450 ms for male participants
and >470 ms for female participants; QRS interval ≥120 ms; PR interval >220 ms;
abnormal conduction; or any other clinically significant abnormalities on a 12-lead
ECG at screening.
11. a history of or current cardiac arrhythmias (eg, 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, coronary heart disease), moderate to severe valvular disease, or
uncontrolled hypertension at screening.
12. 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
protocolspecified 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.
13. any history of or current clinically significant skin disease requiring regular or
periodic treatment.
14. history of clinically relevant drug rash.
15. known allergies, hypersensitivity, or intolerance to JNJ-3989 or its excipients (refer to
the IB).12
16. contraindications to the use of ETV, tenofovir disoproxil, or TAF per local prescribing
information.
17. taken any disallowed therapies as noted in Section 6.7, Concomitant Therapy before
the planned first dose of study intervention.
18. received an investigational intervention (including investigational vaccines) or used
any invasive investigational medical device within 6 months before the planned first
dose of study intervention or is currently enrolled in an investigational study with an
investigational intervention.
19. received anti-HDV treatment (investigational or approved) and/or anti-HBV treatment
(investigational or approved IFN treatment) within 6 months before the planned first
dose of study intervention.
20. female participants who are pregnant, or breastfeeding, or planning to become
pregnant while enrolled in this study or within 90 days after the last dose of study
intervention.
21. male participants who plan to father a child while enrolled in this study or within
90 days after the last dose of study intervention.
22. had major surgery, (eg, requiring general anesthesia) within 12 weeks before
screening, or will not have fully recovered from surgery, or has surgery planned
during the time the participant is expected to participate in the study.
Note: Participants with planned surgical procedures to be conducted under local
anesthesia may participate.
23. have received an organ transplant (except for skin, hair, or cornea transplants).
24. 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.
25. vulnerable participants (eg, incarcerated individuals, individuals under a legal
protection measure).
26. alcohol or drug abuse within 12 months of screening, judged by the investigator to
likely interfere with clinical assessments.
NOTE: Investigators should ensure that all study enrollment criteria have been met at
screening. If a participant's clinical status changes (including any available laboratory results
or receipt of additional medical records) after screening but before the first dose of study
intervention is given such that he or she no longer meets all eligibility criteria, then the
participant should be excluded from participation in the study. Section 5.4, Screen Failures,
describes options for retesting. The required source documentation to support meeting the
enrollment criteria are noted in Section 10.3, Appendix 3, Regulatory, Ethical, and Study
Oversight Considerations.
1. Participants with evidence of hepatitis A virus infection (hepatitis A antibody
immunoglobulin M [IgM]), hepatitis C virus (HCV) infection (HCV antibody), or
hepatitis E virus (HEV) infection (hepatitis E antibody IgM), or human
immunodeficiency virus type 1 (HIV-1) or HIV type 2 (HIV-2) infection (confirmed
by antibodies) at screening.
Note:
− 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.
− 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.
2. any of the following laboratory abnormalities within 12 months prior to screening or
at time of screening:
a. Total bilirubin >1.7x ULN,
b. Direct bilirubin >1.4x ULN,
c. Prothrombin time >1.3x ULN,
d. Serum albumin <3.2 g/dL.
3. history or evidence of clinical signs/symptoms of hepatic decompensation including but not limited to: portal hypertension, ascites, hepatic encephalopathy.
Note: Participants with uncomplicated splenomegaly may be enrolled after
consultation with the sponsor.
4. Child-Pugh score >6.
5. evidence of liver disease of non-HDV or 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,
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/HDV or non-viral liver disease considered clinically significant by the
investigator.
6. 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).
7. 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 (eGFR) ≥grade 3 (ie, <60 mL/min/1.73 m2)
at screening, calculated by the Chronic Kidney Disease Epidemiology
Collaboration (CKD-EPI) formula,
b. Total amylase ≥grade 3,
c. Lipase elevation ≥grade 3,
d. Hemoglobin ≤10.9 g/dL (males), ≤10.4 g/dL (females),
e. Platelet count ≤100,000/dL,
f. Alpha-fetoprotein (AFP) >100 ng/mL,
g. Any other laboratory abnormality considered to be clinically significant by the
investigator.
Note: Participants with AFP >ULN (but ≤100 ng/mL) may be eligible if HCC can be
ruled out based on a sensitive imaging study (eg, enhanced ultrasound, CT, or MRI)
during screening.
8. hemoglobin A1c >8% at screening.
9. 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).
10. abnormal sinus rhythm (heart rate <45 or >100 beats per minute [bpm]); QT interval
corrected for heart rate according to Fridericia (QTcF) >450 ms for male participants
and >470 ms for female participants; QRS interval ≥120 ms; PR interval >220 ms;
abnormal conduction; or any other clinically significant abnormalities on a 12-lead
ECG at screening.
11. a history of or current cardiac arrhythmias (eg, 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, coronary heart disease), moderate to severe valvular disease, or
uncontrolled hypertension at screening.
12. 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
protocolspecified 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.
13. any history of or current clinically significant skin disease requiring regular or
periodic treatment.
14. history of clinically relevant drug rash.
15. known allergies, hypersensitivity, or intolerance to JNJ-3989 or its excipients (refer to
the IB).12
16. contraindications to the use of ETV, tenofovir disoproxil, or TAF per local prescribing
information.
17. taken any disallowed therapies as noted in Section 6.7, Concomitant Therapy before
the planned first dose of study intervention.
18. received an investigational intervention (including investigational vaccines) or used
any invasive investigational medical device within 6 months before the planned first
dose of study intervention or is currently enrolled in an investigational study with an
investigational intervention.
19. received anti-HDV treatment (investigational or approved) and/or anti-HBV treatment
(investigational or approved IFN treatment) within 6 months before the planned first
dose of study intervention.
20. female participants who are pregnant, or breastfeeding, or planning to become
pregnant while enrolled in this study or within 90 days after the last dose of study
intervention.
21. male participants who plan to father a child while enrolled in this study or within
90 days after the last dose of study intervention.
22. had major surgery, (eg, requiring general anesthesia) within 12 weeks before
screening, or will not have fully recovered from surgery, or has surgery planned
during the time the participant is expected to participate in the study.
Note: Participants with planned surgical procedures to be conducted under local
anesthesia may participate.
23. have received an organ transplant (except for skin, hair, or cornea transplants).
24. 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.
25. vulnerable participants (eg, incarcerated individuals, individuals under a legal
protection measure).
26. alcohol or drug abuse within 12 months of screening, judged by the investigator to
likely interfere with clinical assessments.
NOTE: Investigators should ensure that all study enrollment criteria have been met at
screening. If a participant's clinical status changes (including any available laboratory results
or receipt of additional medical records) after screening but before the first dose of study
intervention is given such that he or she no longer meets all eligibility criteria, then the
participant should be excluded from participation in the study. Section 5.4, Screen Failures,
describes options for retesting. The required source documentation to support meeting the
enrollment criteria are noted in Section 10.3, Appendix 3, Regulatory, Ethical, and Study
Oversight Considerations.
The Estimated Number of Participants
-
Taiwan
15 participants
-
Global
50 participants
