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)

Healthy Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02662712
• Other study ID #: CR108092
• Secondary ID: 56136379HPB10012
• Status: Completed
• Phase: Phase 1
• Start date: December 17, 2015
• Est. completion date: June 29, 2018

Study information

• Verified date: July 2019
• Source: Janssen Sciences Ireland UC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 87
• Est. completion date: June 29, 2018
• Est. primary completion date: June 29, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• 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).
• 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).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Sciences Ireland UC

Countries where clinical trial is conducted

Belgium,  Bulgaria,  France,  Georgia,  Germany,  Malaysia,  Moldova, Republic of,  Romania,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Part 2: Change From Baseline in Mean Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA)	HBV DNA will be quantified using an in vitro nucleic acid amplification test for the quantification of HBV DNA.	Up to week 12
Secondary	Part 2: Maximum Decrease in HBV DNA (Baseline-subtracted Mean)	HBV DNA will be quantified using an in vitro nucleic acid amplification test for the quantification of HBV DNA.	Up to week 12
Secondary	Part 2: Changes in Hepatitis B Surface Antigen (HBsAg) Levels	Quantitative HBsAg and levels will be determined from samples using standard serologic assays.	Up to week 12
Secondary	Part II: Percentage of Participants with Treatment Emerging Mutations	Treatment induced emerging mutations will be assessed by comparing the HBV genome sequence obtained at baseline with sequences obtained post-baseline.	Up to week 12
Secondary	Part II: Change From Baseline in HBV DNA (Antiviral Activity) in Chronic Hepatitis B (CHB) Participants with Sequence Variations in the HBV Genome	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.	Up to week 12