Clinical Trials List
Protocol Number56136379HPB1001
NCT Number(ClinicalTrials.gov Identfier)NCT02662712
2017-01-01 - 2018-12-31
Phase I
Terminated5
ICD-10B18.9
Chronic viral hepatitis, unspecified
A Phase 1, double-blind, randomized, placebo-controlled, first-in-human study of orally administered JNJ-56136379 to evaluate safety, tolerability and pharmacokinetics after single ascending doses and one multiple dose regimen in healthy subjects (Part I), and after multiple dose regimens in subjects with chronic hepatitis B (Part II)
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Trial Applicant
Johnson & Johnson
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Sponsor
Janssen Research & Development, LLC
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 林志郎 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Chau-Ting Yeh Digestive System Department
- Chao-Wei Hsu Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 呂宜達 Digestive System Department
- CHUNG-HSIN CHANG Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Jia-Horng Kao Division of General Internal Medicine
- 蘇東弘 Division of General Internal Medicine
- 楊宏志 Division of General Internal Medicine
- Chun-Jen Liu Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- Chung-Feng Huang Digestive System Department
- Jee-Fu Huang Digestive System Department
- Chia-Yen Dai Digestive System Department
- Ming-Lun Yeh Digestive System Department
- Ming-Lung Yu Digestive System Department
- 黃駿逸 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Chronic hepatitis B
Objectives
The purpose of this trial is to evaluate pharmacokinetics and safety data, including serious and other adverse events, physical examination, vital signs, 12-lead electrocardiogram (ECG) and clinical laboratory test results (including biochemical, hematology and urine an examination).
1. To evaluate the safety and tolerability of JNJ-56136379 in healthy subjects after increasing single doses
in fasted condition, after one single dose in the fed condition, and after one multiple dose regimen (Part I).
2. To evaluate the safety and tolerability of JNJ-56136379 in chronic hepatitis B (CHB) subjects after
multiple dose regimens (Part II).
3. To evaluate the pharmacokinetics of JNJ-56136379 in healthy subjects (Part I) and in CHB subjects
(Part II) after single and multiple dosing.
Test Drug
JNJ-56136379
Active Ingredient
JNJ-56136379
Dosage Form
tablet
Dosage
5、25、100
Endpoints
Outcome indicators: Part 2: The number of participants who had adverse events and serious adverse events during treatment
Timeline: Until the 12th week
Explanation: Adverse events (AE) are the adverse medical conditions of participants who received the trial drug, regardless of the possibility of causality. A serious adverse event (SAE) is an AE that causes any of the following results or is deemed to be significant for any other reason: death; initiation or extension of hospital stay; occurrence of a life-threatening situation (immediate risk of death); persistent or major disability/loss Yes; congenital abnormalities.
Security question: Yes
Outcome indicators: Part 2: Number of participants with abnormal physical examination
Timeline: Until the 8th week
Description: Physical examination (including weight measurement and skin examination) will be performed.
Outcome indicators: Part 2: Number of participants with abnormal vital signs
Timeline: Until the 8th week
Description: Vital signs (SBP, DBP, pulse rate: supine and standing) will be measured.
Security question: Yes
Outcome indicators: Part 2: Number of participants with major clinical laboratory findings
Abnormal laboratory tests will be determined according to the standards specified by the World Health Organization (WHO) Toxicity Rating Scale, and the normal range of the clinical laboratory will be used as the basis.
Security question: Yes
Result indicators: Part 2: Maximum Observed Value of Plasma Concentration (Cmax)
Time course: before medication on the first day, 8, 12 hr after medication; after medication on the 28th day
Note: Cmax is the maximum observed value of plasma concentration.
Security issues: No
Result indicators: Part 2: The area under the curve from time 0 to the last measurable concentration time (AUClast)
Time course: before medication on the first day, 8, 12 hr after medication; after medication on the 28th day
Note: AUClast is the area under the curve from time 0 to the last measurable concentration time.
Security issues: No
Result indicators: Part 2: Area under the curve from time 0 to time infinity (AUC infinity)
Time course: before medication on the first day, 8, 12 hr after medication; after medication on the 28th day
Explanation: AUC infinity is the area under the curve from time 0 to time infinity.
Security issues: No
Timeline: Until the 12th week
Explanation: Adverse events (AE) are the adverse medical conditions of participants who received the trial drug, regardless of the possibility of causality. A serious adverse event (SAE) is an AE that causes any of the following results or is deemed to be significant for any other reason: death; initiation or extension of hospital stay; occurrence of a life-threatening situation (immediate risk of death); persistent or major disability/loss Yes; congenital abnormalities.
Security question: Yes
Outcome indicators: Part 2: Number of participants with abnormal physical examination
Timeline: Until the 8th week
Description: Physical examination (including weight measurement and skin examination) will be performed.
Outcome indicators: Part 2: Number of participants with abnormal vital signs
Timeline: Until the 8th week
Description: Vital signs (SBP, DBP, pulse rate: supine and standing) will be measured.
Security question: Yes
Outcome indicators: Part 2: Number of participants with major clinical laboratory findings
Abnormal laboratory tests will be determined according to the standards specified by the World Health Organization (WHO) Toxicity Rating Scale, and the normal range of the clinical laboratory will be used as the basis.
Security question: Yes
Result indicators: Part 2: Maximum Observed Value of Plasma Concentration (Cmax)
Time course: before medication on the first day, 8, 12 hr after medication; after medication on the 28th day
Note: Cmax is the maximum observed value of plasma concentration.
Security issues: No
Result indicators: Part 2: The area under the curve from time 0 to the last measurable concentration time (AUClast)
Time course: before medication on the first day, 8, 12 hr after medication; after medication on the 28th day
Note: AUClast is the area under the curve from time 0 to the last measurable concentration time.
Security issues: No
Result indicators: Part 2: Area under the curve from time 0 to time infinity (AUC infinity)
Time course: before medication on the first day, 8, 12 hr after medication; after medication on the 28th day
Explanation: AUC infinity is the area under the curve from time 0 to time infinity.
Security issues: No
Inclution Criteria
1. Subjects must be a man or a woman between 20 and 55 years of age, extremes included.
2. Female subject must not be of childbearing potential.
3. Female subjects, except for postmenopausal women, should have a negative serum pregnancy test at
screening.
4. Male subjects must agree to comply with contraceptive measures as mentioned in protocol Section
4.3.
5. Subjects must be non-smoking for at least 3 months prior to screening.
6. Subjects must have a body mass index (BMI; weight in kg divided by the square of height in
meters) of 18.0 to 30.0 kg/m2, extremes included.12
7. Subjects must have signed an ICF indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study before starting any screening
activities.
8. Subjects must be willing/able to adhere to the prohibitions and restrictions specified in the protocol
and study procedures.
9. Subjects must have a normal 12-lead ECG (based on the mean value of the triplicate parameters) at
screening including: normal sinus rhythm.
10. Subjects must be healthy on the basis of a medical evaluation that reveals the absence of any
clinically relevant abnormality and includes a physical examination, medical history, vital signs, and
the results of blood biochemistry, blood coagulation and hematology tests and a urinalysis performed
at screening. If there are abnormalities, the subject may be included only if the Investigator judges the
abnormalities or deviations from normal to be not clinically significant or to be appropriate and
reasonable for the population under study. This determination must be recorded in the subject's source
documents and initiated by the Investigator.
11. Subjects must have presence of HBsAg.
12. Subjects must have ALT and AST <2.5 × upper limit of laboratory normal range (ULN) for at
least 3 months prior to screening, with at least one available assessment at least 3 months before
screening, and confirmed at screening.
13. Subjects must have lack of advanced liver disease, ie, either:
a. Metavir F0-F2 (or comparable histologic scoring system) as determined on a liver biopsy within one
year of the screening visit;
b. a result based on specific radiologic liver disease staging modalities (eg, Fibroscan, AFRI, magnetic
resonance imaging [MRI]-Elastography) compatible with Metavir F0-F2 within 6 months of the
screening visit.
Note: Liver disease staging assessments to determine eligibility may be performed during the
screening period as well.
14. Subjects must have HBV DNA of ≥2,000 IU/mL at screening.
15. Subject has not received prior treatment with any approved or investigational drug for the
treatment of hepatitis B.
Note: prior hepatic treatment with herbal or nutritional products is allowed but should be stopped at
screening.
16. Subjects must have absence of signs of hepatocellular carcinoma on an ultrasound performed
within 2 months before the screening visit or during screening. In case of suspicious findings on
conventional ultrasound the subject may still be eligible if hepatocellular carcinoma has been ruled out by a more specific imaging procedure (contrast enhanced ultrasound, CT or MRI).
17. Subjects must sign a separate ICF in which he/she agrees or disagrees to provide an optional
pharmacogenomic sample. Refusal to give consent for the optional pharmacogenomic research sample
does not exclude a subject from participation in the study.
2. Female subject must not be of childbearing potential.
3. Female subjects, except for postmenopausal women, should have a negative serum pregnancy test at
screening.
4. Male subjects must agree to comply with contraceptive measures as mentioned in protocol Section
4.3.
5. Subjects must be non-smoking for at least 3 months prior to screening.
6. Subjects must have a body mass index (BMI; weight in kg divided by the square of height in
meters) of 18.0 to 30.0 kg/m2, extremes included.12
7. Subjects must have signed an ICF indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study before starting any screening
activities.
8. Subjects must be willing/able to adhere to the prohibitions and restrictions specified in the protocol
and study procedures.
9. Subjects must have a normal 12-lead ECG (based on the mean value of the triplicate parameters) at
screening including: normal sinus rhythm.
10. Subjects must be healthy on the basis of a medical evaluation that reveals the absence of any
clinically relevant abnormality and includes a physical examination, medical history, vital signs, and
the results of blood biochemistry, blood coagulation and hematology tests and a urinalysis performed
at screening. If there are abnormalities, the subject may be included only if the Investigator judges the
abnormalities or deviations from normal to be not clinically significant or to be appropriate and
reasonable for the population under study. This determination must be recorded in the subject's source
documents and initiated by the Investigator.
11. Subjects must have presence of HBsAg.
12. Subjects must have ALT and AST <2.5 × upper limit of laboratory normal range (ULN) for at
least 3 months prior to screening, with at least one available assessment at least 3 months before
screening, and confirmed at screening.
13. Subjects must have lack of advanced liver disease, ie, either:
a. Metavir F0-F2 (or comparable histologic scoring system) as determined on a liver biopsy within one
year of the screening visit;
b. a result based on specific radiologic liver disease staging modalities (eg, Fibroscan, AFRI, magnetic
resonance imaging [MRI]-Elastography) compatible with Metavir F0-F2 within 6 months of the
screening visit.
Note: Liver disease staging assessments to determine eligibility may be performed during the
screening period as well.
14. Subjects must have HBV DNA of ≥2,000 IU/mL at screening.
15. Subject has not received prior treatment with any approved or investigational drug for the
treatment of hepatitis B.
Note: prior hepatic treatment with herbal or nutritional products is allowed but should be stopped at
screening.
16. Subjects must have absence of signs of hepatocellular carcinoma on an ultrasound performed
within 2 months before the screening visit or during screening. In case of suspicious findings on
conventional ultrasound the subject may still be eligible if hepatocellular carcinoma has been ruled out by a more specific imaging procedure (contrast enhanced ultrasound, CT or MRI).
17. Subjects must sign a separate ICF in which he/she agrees or disagrees to provide an optional
pharmacogenomic sample. Refusal to give consent for the optional pharmacogenomic research sample
does not exclude a subject from participation in the study.
Exclusion Criteria
Healthy Subjects:
1. Subjects with a past history of cardiac arrhythmias (eg, extrasystoli, tachycardia at rest), history of
risk factors for Torsade de Pointes syndrome (eg, hypokalemia, family history of long QT Syndrome).
2. Female subjects who are breastfeeding at screening.
3. Subjects with a history or evidence of use of alcohol, barbiturates, amphetamines, recreational or
narcotic drug use within the past 1 year, which in the Investigator’s opinion would compromise
subject’s safety and/or compliance with the study procedures.
4. Subjects with current human immunodeficiency virus type 1 (HIV-1) or HIV-2 infection (confirmed
by antibodies) at screening.
5. Subjects with current hepatitis A infection (confirmed by hepatitis A antibody immunoglobulin M
[IgM]), or HBV infection (confirmed by HBsAg), or hepatitis C virus (HCV) infection (confirmed by
HCV antibody), or hepatitis E infection (confirmed by hepatitis E antibody IgM) at screening.
6. Subjects having a positive urine drug test at screening. Urine will be tested for the presence of
amphetamines, benzodiazepines, cocaine, cannabinoids, opioids, methadone and barbiturates.
7. Subject has a history of any illness that, in the opinion of the Investigator, might confound the
results of the study or pose an additional risk in administering study drug to the subject or that could
prevent, limit or confound the protocol specified assessments.
8. Subjects with any history of clinically significant skin disease such as, but not limited to, dermatitis,
eczema, drug rash, psoriasis, food allergy, and urticaria.
9. Subjects with a history of clinically significant drug allergy such as, but not limited to, sulfonamides
and penicillins, or drug allergy witnessed in previous studies with experimental drugs.
10. Subjects using disallowed therapies as specified in the sections Prohibitions and Restrictions
(Section 4.3) and Concomitant Therapy (Section 8).
11. Subjects having received an investigational agent (small molecules) or vaccine within 30 days, or
having received a biological product within 3 months or 5 half-lives (whichever is longer) prior to baseline (first intake of study drugs).
12. Subjects participating in another clinical or medical research study.
13. Subjects having donated or lost more than 1 unit of blood (500 mL) within 60 days or more than
one unit of plasma within 7 days before baseline (first intake of study drugs).
14. Vulnerable subjects (eg, incarcerated individuals).
15. Subject is an employee of Johnson & Johnson, 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.
16. Subjects with known allergy or hypersensitivity to any of the components of the formulation used.
17. Subjects with lack of good/reasonable venous access.
18. Subjects with one or more of the following laboratory abnormalities at screening as defined by the
World Health Organization (WHO) Toxicity Grading Scale (Attachment 1):
Serum creatinine elevation grade 1 or greater (≥1.1 x ULN);
Pancreatic amylase or lipase elevation grade 2 or greater (>1.5 x ULN);Hemoglobin lowering grade
1 or greater (≤10.5 g/dL);
Platelet count lowering grade 1 or greater ( ≤9/L); 99,000 x 10
Absolute neutrophil count lowering grade 1 or greater (≤1500/mm³);
AST or ALT elevation grade 1 or greater ( ≥1.25 x ULN);
Total bilirubin outside the normal range;
Any other toxicity grade 2 or greater.
19. Subjects with positivity of anti-HBs antibodies.
20. Subjects with any evidence of hepatic decompensation (history or current evidence of ascites,
hepatic encephalopathy, hypoalbuminemia, hyperbilirubinemia or coagulopathy).
21. Subjects with any evidence of portal hypertension, especially any endoscopic signs of portal
hypertension as eg, esophageal varices.
22. Subjects with any liver disease of non-HBV etiology. This includes but is not limited to hepatitis
virus infections mentioned in exclusion criterion 5 (excluding HBV infection), drug- or alcohol-related
liver disease, autoimmune hepatitis, hemochromatosis, Wilson’s disease, α-1 antitrypsin deficiency,
primary biliary cirrhosis, primary sclerosing cholangitis or any other non-HBV liver disease
1. Subjects with a past history of cardiac arrhythmias (eg, extrasystoli, tachycardia at rest), history of
risk factors for Torsade de Pointes syndrome (eg, hypokalemia, family history of long QT Syndrome).
2. Female subjects who are breastfeeding at screening.
3. Subjects with a history or evidence of use of alcohol, barbiturates, amphetamines, recreational or
narcotic drug use within the past 1 year, which in the Investigator’s opinion would compromise
subject’s safety and/or compliance with the study procedures.
4. Subjects with current human immunodeficiency virus type 1 (HIV-1) or HIV-2 infection (confirmed
by antibodies) at screening.
5. Subjects with current hepatitis A infection (confirmed by hepatitis A antibody immunoglobulin M
[IgM]), or HBV infection (confirmed by HBsAg), or hepatitis C virus (HCV) infection (confirmed by
HCV antibody), or hepatitis E infection (confirmed by hepatitis E antibody IgM) at screening.
6. Subjects having a positive urine drug test at screening. Urine will be tested for the presence of
amphetamines, benzodiazepines, cocaine, cannabinoids, opioids, methadone and barbiturates.
7. Subject has a history of any illness that, in the opinion of the Investigator, might confound the
results of the study or pose an additional risk in administering study drug to the subject or that could
prevent, limit or confound the protocol specified assessments.
8. Subjects with any history of clinically significant skin disease such as, but not limited to, dermatitis,
eczema, drug rash, psoriasis, food allergy, and urticaria.
9. Subjects with a history of clinically significant drug allergy such as, but not limited to, sulfonamides
and penicillins, or drug allergy witnessed in previous studies with experimental drugs.
10. Subjects using disallowed therapies as specified in the sections Prohibitions and Restrictions
(Section 4.3) and Concomitant Therapy (Section 8).
11. Subjects having received an investigational agent (small molecules) or vaccine within 30 days, or
having received a biological product within 3 months or 5 half-lives (whichever is longer) prior to baseline (first intake of study drugs).
12. Subjects participating in another clinical or medical research study.
13. Subjects having donated or lost more than 1 unit of blood (500 mL) within 60 days or more than
one unit of plasma within 7 days before baseline (first intake of study drugs).
14. Vulnerable subjects (eg, incarcerated individuals).
15. Subject is an employee of Johnson & Johnson, 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.
16. Subjects with known allergy or hypersensitivity to any of the components of the formulation used.
17. Subjects with lack of good/reasonable venous access.
18. Subjects with one or more of the following laboratory abnormalities at screening as defined by the
World Health Organization (WHO) Toxicity Grading Scale (Attachment 1):
Serum creatinine elevation grade 1 or greater (≥1.1 x ULN);
Pancreatic amylase or lipase elevation grade 2 or greater (>1.5 x ULN);Hemoglobin lowering grade
1 or greater (≤10.5 g/dL);
Platelet count lowering grade 1 or greater ( ≤9/L); 99,000 x 10
Absolute neutrophil count lowering grade 1 or greater (≤1500/mm³);
AST or ALT elevation grade 1 or greater ( ≥1.25 x ULN);
Total bilirubin outside the normal range;
Any other toxicity grade 2 or greater.
19. Subjects with positivity of anti-HBs antibodies.
20. Subjects with any evidence of hepatic decompensation (history or current evidence of ascites,
hepatic encephalopathy, hypoalbuminemia, hyperbilirubinemia or coagulopathy).
21. Subjects with any evidence of portal hypertension, especially any endoscopic signs of portal
hypertension as eg, esophageal varices.
22. Subjects with any liver disease of non-HBV etiology. This includes but is not limited to hepatitis
virus infections mentioned in exclusion criterion 5 (excluding HBV infection), drug- or alcohol-related
liver disease, autoimmune hepatitis, hemochromatosis, Wilson’s disease, α-1 antitrypsin deficiency,
primary biliary cirrhosis, primary sclerosing cholangitis or any other non-HBV liver disease
The Estimated Number of Participants
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Taiwan
20 participants
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Global
84 participants
