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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03439488
Other study ID # JNJ-440-1301
Secondary ID JNJ-440-13012017
Status Completed
Phase Phase 1
First received
Last updated
Start date March 26, 2018
Est. completion date October 10, 2019

Study information

Verified date December 2019
Source Alios Biopharma Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and tolerability of JNJ-440 in healthy and Chronic Hepatitis B (CHB) participants after single and multiple doses; and to evaluate the pharmacokinetic (PK) of JNJ-440 in healthy participants and in CHB participants following single and multiple dose regimens, administered alone (healthy participants and CHB participants).


Recruitment information / eligibility

Status Completed
Enrollment 130
Est. completion date October 10, 2019
Est. primary completion date October 10, 2019
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 55 Years
Eligibility Inclusion Criteria:

Inclusion Criteria for Healthy Participants:

- Female participants (except for postmenopausal women) must have a negative pregnancy test at screening and on Day -1

- Participants must have a body mass index (BMI; weight in kilogram [kg] divided by the square of height in meters) of 18.0 to 30.0 kilogram per meter square (kg/m^2), extremes included

- Participants must agree not to donate blood during the study and for at least 1 month after the completion of study drug administration

Inclusion Criteria for Participants with Chronic Hepatitis B (CHB):

- Participant must have CHB infection documented by: (a) Serum hepatitis B surface antigen (HBsAg) positive at screening and at least 6 months prior to screening; (b) Serum antibody immunoglobulin M (IgM) anti-HBc antibody negative at screening

- Participants must currently not be receiving any CHB treatment at screening, that is, have never received treatment with hepatitis B virus (HBV) antiviral medicines, nucleos(t)ide analog (NAs), interferon (IFN) products, or investigational anti-HBV agents, OR Have not been on treatment with HBV antiviral medicines, NAs, or IFN products within 6 months prior to baseline (first intake of study drugs)

Exclusion Criteria:

Exclusion Criteria for Healthy Participants:

- Participants with a past history of cardiac arrhythmias (example, extrasystoli, tachycardia at rest), history of risk factors for Torsade de Pointes syndrome (example, hypokalemia, family history of long QT Syndrome) or history or other clinical evidence of significant or unstable cardiac disease (example, angina, congestive heart failure, myocardial infarction, diastolic dysfunction, significant arrhythmia, coronary heart disease, and/or clinically significant electrocardiogram [ECG] abnormalities), moderate to severe valvular disease or uncontrolled hypertension at screening. Any evidence of heart block or bundle branch block is also exclusionary

- Participants with any history of confirmed clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, and urticarial

- Participants with a history of confirmed clinically significant drug allergy such as, but not limited to, sulfonamides and penicillins, or drug allergy witnessed in previous studies with experimental drugs

Exclusion Criteria for Participants with CHB:

- Participant with positivity of anti-HBs antibodies

- Participants with current hepatitis D virus (HDV) infection (confirmed by HDV antibody) at screening

Study Design


Intervention

Drug:
JNJ-440
JNJ-440 will be administered as oral tablets in Parts 1, 2 and 3. JNJ-440 may be provided as oral solution in a cohort in Part 1.
Placebo
Matching placebo as oral tablets will be administered in Parts 1, 2 and 3.

Locations

Country Name City State
Korea, Republic of Seoul National University Hospital Seoul
Korea, Republic of Severance Hospital, Yonsei University Health System Seoul
Moldova, Republic of Republican Clinical Hospital Chisnau
New Zealand Auckland Clinical Services Auckland
Thailand Research Unit of Hepatitis and Liver Cancer, Department.Biochemistry, Faculty of Medicine King Chulalongkorn Memorial Hospital Bangkok
Thailand Srinagarind Hospital Department of Gastroenterology, Faculty of Medicine, Khon Kaen University Khon Kaen
Ukraine Limited Liability Company "ARENSIA EXPLORATORY MEDICINE" Kapitanavka

Sponsors (1)

Lead Sponsor Collaborator
Alios Biopharma Inc.

Countries where clinical trial is conducted

Korea, Republic of,  Moldova, Republic of,  New Zealand,  Thailand,  Ukraine, 

Outcome

Type Measure Description Time frame Safety issue
Primary Parts 1, 2, and 3: Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability Number of participants with AE (any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship) will be reported. Approximately up to 8 weeks
Primary Parts 1, 2, and 3: Number of Participants With Clinically Significant Changes in Physical Examination (Body Weight Measurement and Skin Examination) A symptom directed physical examination (including body weight measurement and skin examination) will be performed to further assess number of participants with clinically significant changes. Approximately up to 8 weeks
Primary Parts 1, 2, and 3: Number of Participants With Clinically Significant Changes in Vital Signs Number of participants with clinically significant changes in the vital signs will be reported. Approximately up to 8 weeks
Primary Parts 1, 2, and 3: Number of Participants With ECG Abnormalities Number of participants with electrocardiogram (ECG) abnormalities will be reported. Approximately up to 8 weeks
Primary Parts 1, 2, and 3: Number of Participants With Holter Monitoring Abnormalities Number of participants with Holter monitoring abnormalities will be reported. Up to 24 hours post-dose on Day 1
Primary Parts 1, 2, and 3: Number of Participants With Clinical Laboratory Abnormalities Number of participants with clinical laboratory abnormalities will be reported. Approximately up to 8 weeks
Primary Part 1: Maximum Observed Plasma Concentration (Cmax) The Cmax is the maximum observed plasma concentration. Day 1 (predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose)
Primary Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time. Day 1 (predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose)
Primary Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant. Day 1 (predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose)
Primary Part 3: Maximum Observed Plasma Concentration (Cmax) The Cmax is the maximum observed plasma concentration. Day 1 (predose, and at 0.5, 1, 2, 4, 8, and 12 hours post dose), morning predose on Days 2, 15 and 21, and Day 28 (predose, and at 0.5, 1, 2, 4, 8, and 12 hours postdose; 24 hours postdose [once daily {QD} dosing only])
Primary Part 3: Observed Plasma Concentration From Time 0 to tau Hours Postdose (C[0-tau]) C(0-tau) is defined as the observed plasma concentration from time 0 to tau hours postdose (tau = dosing interval). Day 1 (predose, and at 0.5, 1, 2, 4, 8, and 12 hours post dose), morning predose on Days 2, 15 and 21, and Day 28 (predose, and at 0.5, 1, 2, 4, 8, and 12 hours postdose; 24 hours postdose [QD dosing only])
Primary Part 3: Area Under the Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption. Day 1 (predose, and at 0.5, 1, 2, 4, 8, and 12 hours post dose), morning predose on Days 2, 15 and 21, and Day 28 (predose, and at 0.5, 1, 2, 4, 8, and 12 hours postdose; 24 hours postdose [QD dosing only])
Secondary Part 1: Ratio of Cmax Values Between Test and Reference Ratio (Cmax, test/reference) for Different Dosage Forms Ratio Cmax, test/reference is the ratio of individual Cmax values between test and reference treatment. Test = JNJ-440 in oral solution (Cohort 9) or tablet (Cohort 10), and reference = JNJ-440 in fasted conditions (Cohort 2 or Cohort 4-7 [depending on dose], respectively). Day 1 (predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose)
Secondary Part 1: Ratio of AUC(0-last) Values Between Test and Reference (Ratio AUC[0-last],test/reference) for Different Dosage Forms Ratio AUC(0-last),test/ref is the ratio of individual AUC(0-last) values between test and reference treatment. Test = JNJ-440 in oral solution (Cohort 9) or tablet (Cohort 10), and reference = JNJ-440 in fasted conditions (Cohort 2 or Cohort 4-7 [depending on dose], respectively). Day 1 (predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose)
Secondary Part 1: Ratio of AUC(0-infinity) Values Between Test and Reference (Ratio AUC[0-infinity], test/reference) for Different Dosage Forms Ratio AUC(0-infinity),test/ref is the ratio of individual AUC(0-infinity) values between test and reference treatment. Test = JNJ-440 in oral solution (Cohort 9) or tablet (Cohort 10), and ref = JNJ-440 in fasted conditions (Cohort 2 or Cohort 4-7 [depending on dose], respectively). Day 1 (predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose)
Secondary Part 1: Ratio of Cmax Values Between Fed and Fasted (Ratio Cmax, test/reference) Conditions Ratio Cmax, test/reference is the ratio of individual Cmax values between test and reference treatment. Test = JNJ-440 in fed conditions (Cohort 8), and reference = JNJ-440 in fasted conditions (Cohort 3). Day 1 (predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose)
Secondary Part 1: Ratio of AUC(0-last) Values Between Fed and Fasted (Ratio AUC[0- last],test/reference) Ratio AUC(0-last),test/ref is the ratio of individual AUC(0-last) values between test and reference treatment. Test = JNJ-440 in fed conditions (Cohort 8), and ref = JNJ-440 in fasted conditions (Cohort 3). Day 1 (predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose)
Secondary Part 1: Ratio of AUC(0-infinity) Values Between Fed and Fasted (Ratio AUC[0-infinity], test/reference) Ratio AUC(0-infinity),test/ref is the ratio of individual AUC(0- infinity) values between test and reference treatment. Test = JNJ-440 in fed conditions (Cohort 8), and ref = JNJ-440 in fasted conditions (Cohort 3). Day 1 (predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, and 120 hours postdose)
Secondary Part 3: Mean Change from Baseline in HBV DNA Levels Changes of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels as assessed by mean change from baseline in HBV DNA will be evaluated. Baseline up to Day 56
Secondary Part 3: Percentage of Participants with HBV DNA Levels and Undetectable HBV DNA Percentage of participants with HBV DNA levels such as less than (<) 100 international units per milliliter (IU/mL) and undetectable HBV DNA will be evaluated. Baseline up to Day 56
Secondary Part 3: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels The difference of HBsAg levels from baseline will be evaluated. Baseline up to Day 56
Secondary Part 3: Change From Baseline in Hepatitis B e Antigen (HBeAg) Levels The difference of HBeAg levels from baseline will be evaluated. Baseline up to Day 56
Secondary Part 3: Relationship Between Plasma Concentration and Antiviral Activity The potential association between antiviral activity (like HBV DNA or HBsAg or HBeAg) and plasma concentration of JNJ-440 will be assessed. Up to Day 56
Secondary Part 3: Relationship Between Plasma Concentration and Select AEs or Laboratory Changes The potential association between select AEs or laboratory changes and plasma concentration of JNJ-440 may be assessed. Based on the clinically relevant AEs or laboratory changes during the study, this analysis may be performed. Up to Day 56
Secondary Part 3: 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 and compared between participants with and without HBV sequence variations. Baseline up to Day 56
Secondary Part 3: Number of Participants with Emergence of Treatment Associated Mutations in the HBV Genome Treatment induced emerging mutations will be assessed by comparing the HBV genome sequence obtained at baseline with sequences obtained post-baseline. Baseline up to Day 29
Secondary Parts 1, 2, and 3: Relationship Between JNJ-440 Plasma Concentrations and Time-Matched Change from Baseline QTcF The relationship between plasma levels of JNJ-440 and Q-T interval corrected for heart rate according to Fridericia's formula (QTcF) exposure response relationship will be assessed. Approximately up to 18 weeks
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