Clinical trial NCT02662712: A Study of Orally Administered JNJ-56136379 to Evaluate Safety, Tolerability and Pharmacokinetics After Single Ascending Doses and One Multiple Dose Regimen in Healthy Participants (Part I), and After Multiple Dose Regimens in Participants With Chronic Hepatitis B (Part II)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Hepatitis, Chronic
Keywords: Healthy
Hepatitis, Chronic
JNJ-56136379
Placebo
Lead sponsor: Janssen Sciences Ireland UC
Sponsor class: INDUSTRY
First posted: 2016-01-25
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Part 1 Single Ascending Dose and Multiple Dose : Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events
timeFrame: Until the last study-related activity (30-35 days after last dosing)
measure: Part 2: Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events
timeFrame: Up to Week 12
measure: Part 1 Single Ascending Dose and Multiple Dose : Number of Participants With Abnormal Physical Examinations
timeFrame: 30-35 days after last study drug intake or after dropout
measure: Part 2: Number of Participants With Abnormal Physical Examinations
timeFrame: Up to Week 8
measure: Part 1 Single Ascending Dose and Multiple Dose : Number of Participants With Abnormal Vital Signs
timeFrame: 30-35 days after last study drug intake or after dropout
measure: Part 2: Number of Participants With Abnormal Vital Signs
timeFrame: Up to Week 8
measure: Part 1 Single Ascending Dose and Multiple Dose : Number of Participants With Clinically Significant Laboratory Findings
timeFrame: 30-35 days after last study drug intake or after dropout
measure: Part 2: Number of Participants With Clinically Significant Laboratory Findings
timeFrame: Up to Week 8
measure: Part 1: Maximum Observed Plasma Concentration (Cmax) After Single Dose Administration
timeFrame: Pre-dose, 0.5 hour (hr), 1, 1.5, 2, 3, 4, 6, 8, 12 and 16 hr post-dose on Day 1
measure: Part 1: Maximum Observed Plasma Concentration (Cmax) After Multiple Dose Administration
timeFrame: Pre-dose, 0.5 hr, 1, 1.5, 2, 3, 4, 6, 8, 12 and 16 hr Day 1; post-dose on Day 12
measure: Part 2: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Pre-dose, 8, 12 hr post-dose on Day 1; post-dose on Day 28
measure: Part 1: Area Under the Curve From Time 0 to the Time of the Last Measurable Concentration (AUClast) After Single Dose Administration
timeFrame: Pre-dose, 0.5 hour (hr), 1, 1.5, 2, 3, 4, 6, 8, 12 and 16 hr post-dose on Day 1
measure: Part 2: Area Under the Curve From Time 0 to the Time of the Last Measurable Concentration (AUClast)
timeFrame: Pre-dose, 8, 12 hr post-dose on Day 1; post-dose on Day 28
measure: Part 1: Area Under the Curve From Time 0 to Infinity (AUC infinity) After Single Dose Administration
timeFrame: Pre-dose, 0.5 hour (hr), 1, 1.5, 2, 3, 4, 6, 8, 12 and 16 hr post-dose on Day 1
measure: Part 2: Area Under the Curve From Time 0 to Infinity (AUC infinity)
timeFrame: Pre-dose, 8, 12 hr post-dose on Day 1; post-dose on Day 28
Secondary outcomes:
measure: Part 2: Change From Baseline in Mean Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA)
timeFrame: Up to week 12
measure: Part 2: Maximum Decrease in HBV DNA (Baseline-subtracted Mean)
timeFrame: Up to week 12
measure: Part 2: Changes in Hepatitis B Surface Antigen (HBsAg) Levels
timeFrame: Up to week 12
measure: Part II: Percentage of Participants with Treatment Emerging Mutations
timeFrame: Up to week 12
measure: Part II: Change From Baseline in HBV DNA (Antiviral Activity) in Chronic Hepatitis B (CHB) Participants with Sequence Variations in the HBV Genome
timeFrame: Up to week 12
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
city: Edegem
country: Belgium
city: Mechelen
country: Belgium
city: Merksem
country: Belgium
city: Sofia
country: Bulgaria
city: Clichy
country: France
city: La Tronche
country: France
city: Lyon
country: France
city: Paris
country: France
city: Tbilisi
country: Georgia
city: Essen
country: Germany
city: Hannover
country: Germany
city: Wiesbaden
country: Germany
city: Kuala Lumpur
country: Malaysia
city: Chisinau
country: Moldova, Republic of
city: Bucuresti
country: Romania
city: Timisoara
country: Romania
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Santander
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Kaohsiung
country: Taiwan
city: Keelung
country: Taiwan
city: Taichung
country: Taiwan
city: Taipei City
country: Taiwan
city: Taoyuan
country: Taiwan
Study officials:
affiliation: Janssen Sciences Ireland UC
name: Janssen Sciences Ireland UC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Zoulim F, Lenz O, Vandenbossche JJ, Talloen W, Verbinnen T, Moscalu I, Streinu-Cercel A, Bourgeois S, Buti M, Crespo J, Manuel Pascasio J, Sarrazin C, Vanwolleghem T, Shukla U, Fry J, Yogaratnam JZ. JNJ-56136379, an HBV Capsid Assembly Modulator, Is Well-Tolerated and Has Antiviral Activity in a Phase 1 Study of Patients With Chronic Infection. Gastroenterology. 2020 Aug;159(2):521-533.e9. doi: 10.1053/j.gastro.2020.04.036. Epub 2020 Apr 25.
citation: Vandenbossche J, Jessner W, van den Boer M, Biewenga J, Berke JM, Talloen W, De Zwart L, Snoeys J, Yogaratnam J. Pharmacokinetics, Safety and Tolerability of JNJ-56136379, a Novel Hepatitis B Virus Capsid Assembly Modulator, in Healthy Subjects. Adv Ther. 2019 Sep;36(9):2450-2462. doi: 10.1007/s12325-019-01017-1. Epub 2019 Jul 2.