Healthy, Hepatitis, Chronic
Conditions
Keywords
Healthy, Hepatitis, Chronic, JNJ-56136379, Placebo
Brief summary
The purpose of this study is to evaluate pharmacokinetics and safety data including serious and other adverse events, physical examinations, vital signs, 12-lead electrocardiograms (ECGs) and clinical laboratory results (including biochemistry, hematology, and urine).
Detailed description
Part 1: This is a first-in-human (FIH), double-blind (neither the researchers nor the participants know what treatment the participant is receiving), randomized (study medication assigned to participants by chance), placebo-controlled (an inactive substance; a pretend treatment \[with no drug in it\] that is compared in a clinical trial with a drug to test if the drug has a real effect) study. Part 1 includes healthy adult participants, divided into 3 panels (Panel 1, 2 and 3) and in Part 2 adult Chronic Hepatitis B Participants will be included, in Sessions VIII to XI and Optional Sessions A-B-C (Panel 4). The study will consists of screening phase (part 1: \[less than or equal to \<=28 days before the first intake of study drug; part 2: \[\<=56 to greater than or equal to {\>=} 20 days before the first intake of study drug), Treatment Phase (multiple dose phase in part 1: Day -1 up to 12 or 19 days; part 2: up to 4 weeks) and Follow up Phase (part 1: 30-35 days after last study drug intake or after dropout; part 2: up to week 8 after actual end of study drug treatment). Participants' safety will be evaluated throughout the study.
Interventions
DRUGJNJ-56136379
JNJ-56136379 oral tablets will be given in Part 1 (single dose escalation and multiple dose session) and Part 2 (multiple dose escalation).
DRUGPlacebo
Matching placebo to JNJ-56136379 will be given in Part 1 (single dose escalation and multiple dose session) and Part 2 (multiple dose escalation).
Sponsors
Janssen Sciences Ireland UC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* For Part II, a female participant must be either of a) Non-childbearing potential defined as: 1) Postmenopausal: A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level (greater than (\>)40 international unit per milliliter (IU/L) or milli-international units per milliliter (mIU/mL) in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy, however in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient, or 2) Permanently sterile: Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy, or b) Childbearing potential and practicing sexual abstinence or a highly effective method of contraception from screening onwards and agree to continue to use the same method of contraception throughout study treatment and for at least 90 days after the last dose of study drug (or longer, if dictated by local regulation) * Female participants should have a negative serum pregnancy test at screening * Healthy Participants: Participants must have a body mass index (BMI; weight in kg divided by the square of height in meters) of 18.0 to 30.0 kilogram per square meter (kg/m2), extremes included * Chronic Hepatitis B Participants: Participants must have lack of advanced liver disease, ie, either: Metavir F0-F2 (or comparable histologic scoring system) as determined on a liver biopsy within one year of the screening visit; 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 * Chronic Hepatitis B Participants: Participants must have HBV DNA of greater than or equal \[\>=\] 2,000 international unit per milliliter (IU/mL) at screening * Chronic Hepatitis B Participants: Participants must be aged between 18 years to 65 years, have a body mass index (BMI; weight in kg divided by the square of height in meters) of 18.0 to 35.0 kilogram per square meter (kg/m\^2), extremes included
Exclusion criteria
* Healthy Participants: Participants with a past history of cardiac arrhythmias (example, extrasystolic, tachycardia at rest), history of risk factors for Torsade de Pointes syndrome (eg, hypokalemia, family history of long QT Syndrome) * Healthy Participants: Female participants who are breastfeeding at screening * Healthy Participants: Participants with current human immunodeficiency virus type 1 (HIV-1) or HIV-2 infection (confirmed by antibodies) at screening * Chronic Hepatitis B Participants: Participants with current HCV infection (confirmed by HCV antibody or HCV RNA) or hepatitis delta virus (HDV) infection (confirmed by HDV antibody) at screening * Chronic Hepatitis B Participants: Participants with positivity of anti-HBs antibodies * Chronic Hepatitis B Participants: Participants with a past history of cardiac arrhythmias (eg, extrasystolic, tachycardia at rest), history of risk factors for Torsade de Pointes syndrome (eg, hypokalemia, family history of long QT Syndrome) * Chronic Hepatitis B Participants: Female participants who are breastfeeding at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Area Under the Curve From Time 0 to Infinity (AUC infinity) | Pre-dose, 8, 12 hr post-dose on Day 1; post-dose on Day 28 | AUC infinity is the area under the curve from time 0 to infinity. |
| Part 1: Maximum Observed Plasma Concentration (Cmax) After Multiple Dose Administration | Pre-dose, 0.5 hr, 1, 1.5, 2, 3, 4, 6, 8, 12 and 16 hr Day 1; post-dose on Day 12 | Cmax is the Maximum observed plasma concentration. |
| Part 2: Maximum Observed Plasma Concentration (Cmax) | Pre-dose, 8, 12 hr post-dose on Day 1; post-dose on Day 28 | Cmax is the Maximum observed plasma concentration. |
| Part 1: Area Under the Curve From Time 0 to the Time of the Last Measurable Concentration (AUClast) After Single Dose Administration | Pre-dose, 0.5 hour (hr), 1, 1.5, 2, 3, 4, 6, 8, 12 and 16 hr post-dose on Day 1 | AUClast is the area under the curve from time 0 to the time of the last measurable Concentration. |
| Part 2: Area Under the Curve From Time 0 to the Time of the Last Measurable Concentration (AUClast) | Pre-dose, 8, 12 hr post-dose on Day 1; post-dose on Day 28 | AUClast is the area under the curve from time 0 to the time of the last measurable Concentration. |
| Part 1: Area Under the Curve From Time 0 to Infinity (AUC infinity) After Single Dose Administration | Pre-dose, 0.5 hour (hr), 1, 1.5, 2, 3, 4, 6, 8, 12 and 16 hr post-dose on Day 1 | AUC infinity is the area under the curve from time 0 to infinity. |
| Part 1 Single Ascending Dose and Multiple Dose : Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | Until the last study-related activity (30-35 days after last dosing) | An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. |
| Part 2: Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | Up to Week 12 | An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. |
| Part 1 Single Ascending Dose and Multiple Dose : Number of Participants With Abnormal Physical Examinations | 30-35 days after last study drug intake or after dropout | Physical examinations (including body weight measurement and skin examination) will be performed. |
| Part 2: Number of Participants With Abnormal Physical Examinations | Up to Week 8 | Physical examinations (including body weight measurement and skin examination) will be performed. |
| Part 1 Single Ascending Dose and Multiple Dose : Number of Participants With Abnormal Vital Signs | 30-35 days after last study drug intake or after dropout | Vital signs (Supine Blood Pressure \[SBP\], Diastolic Blood Pressure \[DBP\] pulse rate: supine and standing) will be performed. |
| Part 2: Number of Participants With Abnormal Vital Signs | Up to Week 8 | Vital signs (SBP, DBP pulse rate: supine and standing) will be performed. |
| Part 1 Single Ascending Dose and Multiple Dose : Number of Participants With Clinically Significant Laboratory Findings | 30-35 days after last study drug intake or after dropout | The laboratory abnormalities will be determined according to the criteria specified in the World Health Organization (WHO) Toxicity Grading Scale and in accordance with the normal ranges of the clinical laboratory. |
| Part 2: Number of Participants With Clinically Significant Laboratory Findings | Up to Week 8 | The laboratory abnormalities will be determined according to the criteria specified in the World Health Organization (WHO) Toxicity Grading Scale and in accordance with the normal ranges of the clinical laboratory. |
| Part 1: Maximum Observed Plasma Concentration (Cmax) After Single Dose Administration | Pre-dose, 0.5 hour (hr), 1, 1.5, 2, 3, 4, 6, 8, 12 and 16 hr post-dose on Day 1 | Cmax is the Maximum observed plasma concentration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Maximum Decrease in HBV DNA (Baseline-subtracted Mean) | Up to week 12 | HBV DNA will be quantified using an in vitro nucleic acid amplification test for the quantification of HBV DNA. |
| Part 2: Changes in Hepatitis B Surface Antigen (HBsAg) Levels | Up to week 12 | Quantitative HBsAg and levels will be determined from samples using standard serologic assays. |
| Part II: Percentage of Participants with Treatment Emerging Mutations | Up to week 12 | Treatment induced emerging mutations will be assessed by comparing the HBV genome sequence obtained at baseline with sequences obtained post-baseline. |
| Part II: Change From Baseline in HBV DNA (Antiviral Activity) in Chronic Hepatitis B (CHB) Participants with Sequence Variations in the HBV Genome | Up to week 12 | Sequence variations in the HBV genome will be assessed by sequencing of the viral genome. Antiviral activity will be assessed by measuring change from baseline in HBV DNA concentration using in vitro nucleic acid amplification test for the quantification of HBV DNA and compared between participants with and without HBV sequence variations. |
| Part 2: Change From Baseline in Mean Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) | Up to week 12 | HBV DNA will be quantified using an in vitro nucleic acid amplification test for the quantification of HBV DNA. |
Countries
Belgium, Bulgaria, France, Georgia, Germany, Malaysia, Moldova, Romania, Spain, Taiwan
Outcome results
None listed