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)

NCT02662712 | Completed Phase 1

• 3 other identifiers: CR10809256136379HPB10012015-003724-30
• Study Type: interventional
• Target: 87
• Locations: 10 countries
• Sites: 27

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).

Conditions

Healthy; Hepatitis, Chronic

Keywords

Healthy; Hepatitis, Chronic; JNJ-56136379; Placebo

Outcome Measures

Primary Outcomes (15)

• Part 1 Single Ascending Dose and Multiple Dose : Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events

  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.

  Until the last study-related activity (30-35 days after last dosing)

• Part 2: Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events

  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.

  Up to Week 12

• Part 1 Single Ascending Dose and Multiple Dose : Number of Participants With Abnormal Physical Examinations

  Physical examinations (including body weight measurement and skin examination) will be performed.

  30-35 days after last study drug intake or after dropout

• Part 2: Number of Participants With Abnormal Physical Examinations

  Physical examinations (including body weight measurement and skin examination) will be performed.

  Up to Week 8

• Part 1 Single Ascending Dose and Multiple Dose : Number of Participants With Abnormal Vital Signs

  Vital signs (Supine Blood Pressure \[SBP\], Diastolic Blood Pressure \[DBP\] pulse rate: supine and standing) will be performed.

  30-35 days after last study drug intake or after dropout

• Part 2: Number of Participants With Abnormal Vital Signs

  Vital signs (SBP, DBP pulse rate: supine and standing) will be performed.

  Up to Week 8

• Part 1 Single Ascending Dose and Multiple Dose : Number of Participants With Clinically Significant Laboratory Findings

  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.

  30-35 days after last study drug intake or after dropout

• Part 2: Number of Participants With Clinically Significant Laboratory Findings

  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.

  Up to Week 8

• Part 1: Maximum Observed Plasma Concentration (Cmax) After Single Dose Administration

  Cmax is the Maximum observed plasma concentration.

  Pre-dose, 0.5 hour (hr), 1, 1.5, 2, 3, 4, 6, 8, 12 and 16 hr post-dose on Day 1

• Part 1: Maximum Observed Plasma Concentration (Cmax) After Multiple Dose Administration

  Cmax is the Maximum observed plasma concentration.

  Pre-dose, 0.5 hr, 1, 1.5, 2, 3, 4, 6, 8, 12 and 16 hr Day 1; post-dose on Day 12

• Part 2: Maximum Observed Plasma Concentration (Cmax)

  Cmax is the Maximum observed plasma concentration.

  Pre-dose, 8, 12 hr post-dose on Day 1; post-dose on Day 28

• Part 1: Area Under the Curve From Time 0 to the Time of the Last Measurable Concentration (AUClast) After Single Dose Administration

  AUClast is the area under the curve from time 0 to the time of the last measurable Concentration.

  Pre-dose, 0.5 hour (hr), 1, 1.5, 2, 3, 4, 6, 8, 12 and 16 hr post-dose on Day 1

• Part 2: Area Under the Curve From Time 0 to the Time of the Last Measurable Concentration (AUClast)

  AUClast is the area under the curve from time 0 to the time of the last measurable Concentration.

  Pre-dose, 8, 12 hr post-dose on Day 1; post-dose on Day 28

• Part 1: Area Under the Curve From Time 0 to Infinity (AUC infinity) After Single Dose Administration

  AUC infinity is the area under the curve from time 0 to infinity.

  Pre-dose, 0.5 hour (hr), 1, 1.5, 2, 3, 4, 6, 8, 12 and 16 hr post-dose on Day 1

• Part 2: Area Under the Curve From Time 0 to Infinity (AUC infinity)

  AUC infinity is the area under the curve from time 0 to infinity.

  Pre-dose, 8, 12 hr post-dose on Day 1; post-dose on Day 28

Secondary Outcomes (5)

• Part 2: Change From Baseline in Mean Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA)

  Up to week 12

• Part 2: Maximum Decrease in HBV DNA (Baseline-subtracted Mean)

  Up to week 12

• Part 2: Changes in Hepatitis B Surface Antigen (HBsAg) Levels

  Up to week 12

• Part II: Percentage of Participants with Treatment Emerging Mutations

  Up to week 12

• 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

Study Arms (3)

Part 1: Single Dose Escalation

EXPERIMENTAL

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.

Drug: JNJ-56136379; Drug: Placebo

Part 1: Multiple dose session

EXPERIMENTAL

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.

Drug: JNJ-56136379; Drug: Placebo

Part 2: Multiple dose escalation

EXPERIMENTAL

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.

Drug: JNJ-56136379; Drug: Placebo

Interventions

JNJ-56136379 DRUG

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

Part 1: Multiple dose session; Part 1: Single Dose Escalation; Part 2: Multiple dose escalation

Placebo 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; Part 1: Single Dose Escalation; Part 2: Multiple dose escalation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Sciences Ireland UC: lead

Study Sites (27)

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Brussels, Belgium

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Edegem, Belgium

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Mechelen, Belgium

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Merksem, Belgium

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Sofia, Bulgaria

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Clichy, France

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La Tronche, France

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Lyon, France

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Paris, France

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Tbilisi, Georgia

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Essen, Germany

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Hanover, Germany

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Wiesbaden, Germany

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Kuala Lumpur, Malaysia

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Chisinau, Moldova

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Bucharest, Romania

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Timișoara, Romania

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Barcelona, Spain

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Madrid, Spain

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Santander, Spain

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Seville, Spain

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Valencia, Spain

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Kaohsiung City, Taiwan

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Keelung, Taiwan

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Taichung, Taiwan

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Taipei, Taiwan

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Taoyuan District, Taiwan

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Related Publications (2)

• 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.

  PMID: 32343960 DERIVED

• 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.

  PMID: 31267367 DERIVED

MeSH Terms

Conditions

Hepatitis, Chronic

Interventions

JNJ-56136379

Condition Hierarchy (Ancestors)

Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Janssen Sciences Ireland UC Clinical Trial

  Janssen Sciences Ireland UC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2015
• First Posted: January 25, 2016
• Study Start: December 17, 2015
• Primary Completion: June 29, 2018
• Study Completion: June 29, 2018
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

BU (1); DE (3); BE (4); GE (1); RO (2); MY (1); ES (5); MO (1); TW (5); FR (4)