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)

NCT ID: NCT02662712

Last Updated: 2025-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-17
• Study Completion Date: 2018-06-29

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.

Conditions

Healthy; Hepatitis, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Part 1: Single Dose Escalation

The single dose escalation phase of the study will consist of 6 dosing sessions (Sessions I to VI) evaluated in 2 panels (Panels 1 and 2). The dose of JNJ-56136379 will be consecutively escalated over 5 levels, alternating between the 2 panels. Panel 1 will receive 3 single doses (SD1, SD3 and SD3fed) in Sessions I, III and V, respectively. Panel 2 will receive 3 single doses (SD2, SD4 and SD5) in Sessions II, IV and VI, respectively. There will be a washout period of at least 14 days between consecutive JNJ-56136379/placebo dosing in each individual participant.

Group Type: EXPERIMENTAL

JNJ-56136379

Intervention Type: DRUG

JNJ-56136379 oral tablets will be given in Part 1 (single dose escalation and multiple dose session) and Part 2 (multiple dose escalation).

Placebo

Intervention Type: DRUG

Matching placebo to JNJ-56136379 will be given in Part 1 (single dose escalation and multiple dose session) and Part 2 (multiple dose escalation).

Part 1: Multiple dose session

After completion of the fifth single dose session another panel of healthy participant (panel 3) receive multiple doses of JNJ-56136379 at one dose level (MDx) or placebo for 12 or 19 consecutive days (Session VII) in fed or fasted conditions.

Group Type: EXPERIMENTAL

JNJ-56136379

Intervention Type: DRUG

JNJ-56136379 oral tablets will be given in Part 1 (single dose escalation and multiple dose session) and Part 2 (multiple dose escalation).

Placebo

Intervention Type: DRUG

Matching placebo to JNJ-56136379 will be given in Part 1 (single dose escalation and multiple dose session) and Part 2 (multiple dose escalation).

Part 2: Multiple dose escalation

Multiple dose levels will be given in Panel 4 in Session VIII (European sites), Sessions IX and X (European and/or Asian sites) Session XI (Asian sites) for 28 consecutive days in fed conditions. Optional Sessions A-B-C (Panel 4) used for further dose evaluations at European and/or Asian sites. Per session, participants will receive JNJ 56136379 or placebo. Dose progression to the next multiple dose level may be adapted based on the emerging safety and PK outcome of the previous dosing levels.

Group Type: EXPERIMENTAL

JNJ-56136379

Intervention Type: DRUG

JNJ-56136379 oral tablets will be given in Part 1 (single dose escalation and multiple dose session) and Part 2 (multiple dose escalation).

Placebo

Intervention Type: DRUG

Matching placebo to JNJ-56136379 will be given in Part 1 (single dose escalation and multiple dose session) and Part 2 (multiple dose escalation).

Interventions

JNJ-56136379

JNJ-56136379 oral tablets will be given in Part 1 (single dose escalation and multiple dose session) and Part 2 (multiple dose escalation).

Intervention Type: DRUG

Placebo

Matching placebo to JNJ-56136379 will be given in Part 1 (single dose escalation and multiple dose session) and Part 2 (multiple dose escalation).

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Janssen Sciences Ireland UC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Sciences Ireland UC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Sciences Ireland UC

Locations

Brussels, , Belgium

Edegem, , Belgium

Mechelen, , Belgium

Merksem, , Belgium

Sofia, , Bulgaria

Clichy, , France

La Tronche, , France

Lyon, , France

Paris, , France

Tbilisi, , Georgia

Essen, , Germany

Hanover, , Germany

Wiesbaden, , Germany

Kuala Lumpur, , Malaysia

Chisinau, , Moldova

Bucharest, , Romania

Timișoara, , Romania

Barcelona, , Spain

Madrid, , Spain

Santander, , Spain

Seville, , Spain

Valencia, , Spain

Kaohsiung City, , Taiwan

Keelung, , Taiwan

Taichung, , Taiwan

Taipei, , Taiwan

Taoyuan District, , Taiwan

Countries

Belgium; Bulgaria; France; Georgia; Germany; Malaysia; Moldova; Romania; Spain; Taiwan

References

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.

Reference Type: DERIVED

PMID: 32343960 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31267367 (View on PubMed)

Other Identifiers

56136379HPB1001

Identifier Type: OTHER

Identifier Source: secondary_id

2015-003724-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR108092

Identifier Type: -

Identifier Source: org_study_id