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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT03439488
Registration number
NCT03439488
Ethics application status
Date submitted
23/01/2018
Date registered
20/02/2018
Date last updated
10/12/2019
Titles & IDs
Public title
A Study of Orally Administered JNJ-440 to Evaluate the Safety, Tolerability, and Pharmacokinetics After Single Ascending Doses Including Food Effect Evaluation; After Multi-Day Dosing in Healthy Participants; and After Multiple (Ascending) Doses in Participants With Chronic Hepatitis B
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Scientific title
A Multipart Phase 1, Double-Blind, Randomized, Placebo-Controlled, First-in-Human, Study of Orally Administered JNJ-440 to Evaluate the Safety, Tolerability, and Pharmacokinetics After Single Ascending Doses Including Food Effect Evaluation (Part 1); After Multi-Day Dosing (Part 2) in Healthy Subjects; and After Multiple (Ascending) Doses in Subjects With Chronic Hepatitis B (Part 3)
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Secondary ID [1]
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JNJ-440-1301
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Secondary ID [2]
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JNJ-440-1301
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B
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Condition category
Condition code
Infection
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Other infectious diseases
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Oral and Gastrointestinal
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Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - JNJ-440
Treatment: Drugs - Placebo
Experimental: Part 1 (Healthy Participants): Single Ascending Dose (SAD) - Participants in Cohorts 1 to 5 and 3 optional cohorts (Cohorts 6, 7 and 10) will receive a single dose of JNJ-440/placebo on Day 1. Two cohorts will receive a second dose of JNJ-440/placebo in a fed state (participants from Cohort 3 will also participate in Cohort 8) or as an alternative JNJ-440 formulation (participants from Cohort 2 will also participate in optional Cohort 9) after a washout window of at least 10 days. In Cohorts 1 to 4, study drug will be administered under fasted conditions; in the remaining cohorts, study drug will be administered under fasted/fed conditions depending on the results of the food effect evaluation.
Experimental: Part 2 (Healthy Participants): Multiple Ascending Dose (MAD) - Participants in Cohorts 1 and 2 will receive a once daily dose of JNJ-440/placebo for the duration of 7 days under fasted or fed conditions. Participants in an optional cohort (Cohort 3) may receive a once daily or twice daily dose of JNJ-440/placebo for the duration of 7 or 14 days under fasted or fed conditions. The starting dose for Cohort 1 in Part 2 will be determined by the Sponsor in consultation with the Principal Investigator based on the data from Part 1. Dose escalation will be performed only after review of safety and pharmacokinetic (PK) data after a minimum of 7 days of study drug administration.
Experimental: Part 3 (Chronic Hepatitis B [CHB] Participants): MAD - Participants in Cohorts 1 and 2 and 3 optional cohorts (Cohorts 3, 4, and 5) will receive multiple ascending doses of JNJ-440/placebo once daily or twice daily for 28 days under fed or fasted conditions. The starting dose and formulation for Cohort 1 will be determined based on the review of available data in healthy participants from Part 1 (SAD) and Part 2 (MAD). Dose escalation will be performed only after review of safety, tolerability, and PK data after a minimum of 14 days of study drug administration from at least 8 CHB participants.
Treatment: Drugs: 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.
Treatment: Drugs: Placebo
Matching placebo as oral tablets will be administered in Parts 1, 2 and 3.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Parts 1, 2, and 3: Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability
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Assessment method [1]
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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.
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Timepoint [1]
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Approximately up to 8 weeks
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Primary outcome [2]
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Parts 1, 2, and 3: Number of Participants With Clinically Significant Changes in Physical Examination (Body Weight Measurement and Skin Examination)
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Assessment method [2]
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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.
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Timepoint [2]
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Approximately up to 8 weeks
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Primary outcome [3]
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Parts 1, 2, and 3: Number of Participants With Clinically Significant Changes in Vital Signs
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Assessment method [3]
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Number of participants with clinically significant changes in the vital signs will be reported.
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Timepoint [3]
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Approximately up to 8 weeks
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Primary outcome [4]
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Parts 1, 2, and 3: Number of Participants With ECG Abnormalities
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Assessment method [4]
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Number of participants with electrocardiogram (ECG) abnormalities will be reported.
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Timepoint [4]
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Approximately up to 8 weeks
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Primary outcome [5]
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Parts 1, 2, and 3: Number of Participants With Holter Monitoring Abnormalities
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Assessment method [5]
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Number of participants with Holter monitoring abnormalities will be reported.
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Timepoint [5]
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Up to 24 hours post-dose on Day 1
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Primary outcome [6]
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Parts 1, 2, and 3: Number of Participants With Clinical Laboratory Abnormalities
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Assessment method [6]
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Number of participants with clinical laboratory abnormalities will be reported.
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Timepoint [6]
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Approximately up to 8 weeks
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Primary outcome [7]
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Part 1: Maximum Observed Plasma Concentration (Cmax)
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Assessment method [7]
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The Cmax is the maximum observed plasma concentration.
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Timepoint [7]
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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)
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Primary outcome [8]
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Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
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Assessment method [8]
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The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
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Timepoint [8]
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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)
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Primary outcome [9]
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Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
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Assessment method [9]
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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.
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Timepoint [9]
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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)
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Primary outcome [10]
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Part 3: Maximum Observed Plasma Concentration (Cmax)
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Assessment method [10]
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The Cmax is the maximum observed plasma concentration.
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Timepoint [10]
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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])
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Primary outcome [11]
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Part 3: Observed Plasma Concentration From Time 0 to tau Hours Postdose (C[0-tau])
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Assessment method [11]
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C(0-tau) is defined as the observed plasma concentration from time 0 to tau hours postdose (tau = dosing interval).
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Timepoint [11]
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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])
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Primary outcome [12]
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Part 3: Area Under the Curve From Time Zero to End of Dosing Interval (AUC[0-tau])
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Assessment method [12]
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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.
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Timepoint [12]
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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])
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Secondary outcome [1]
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Part 1: Ratio of Cmax Values Between Test and Reference Ratio (Cmax, test/reference) for Different Dosage Forms
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Assessment method [1]
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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).
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Timepoint [1]
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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)
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Secondary outcome [2]
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Part 1: Ratio of AUC(0-last) Values Between Test and Reference (Ratio AUC[0-last],test/reference) for Different Dosage Forms
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Assessment method [2]
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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).
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Timepoint [2]
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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)
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Secondary outcome [3]
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Part 1: Ratio of AUC(0-infinity) Values Between Test and Reference (Ratio AUC[0-infinity], test/reference) for Different Dosage Forms
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Assessment method [3]
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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).
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Timepoint [3]
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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)
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Secondary outcome [4]
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Part 1: Ratio of Cmax Values Between Fed and Fasted (Ratio Cmax, test/reference) Conditions
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Assessment method [4]
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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).
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Timepoint [4]
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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)
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Secondary outcome [5]
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Part 1: Ratio of AUC(0-last) Values Between Fed and Fasted (Ratio AUC[0- last],test/reference)
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Assessment method [5]
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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).
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Timepoint [5]
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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)
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Secondary outcome [6]
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Part 1: Ratio of AUC(0-infinity) Values Between Fed and Fasted (Ratio AUC[0-infinity], test/reference)
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Assessment method [6]
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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).
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Timepoint [6]
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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)
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Secondary outcome [7]
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Part 3: Mean Change from Baseline in HBV DNA Levels
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Assessment method [7]
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Changes of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels as assessed by mean change from baseline in HBV DNA will be evaluated.
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Timepoint [7]
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Baseline up to Day 56
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Secondary outcome [8]
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Part 3: Percentage of Participants with HBV DNA Levels and Undetectable HBV DNA
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Assessment method [8]
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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.
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Timepoint [8]
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Baseline up to Day 56
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Secondary outcome [9]
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Part 3: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels
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Assessment method [9]
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The difference of HBsAg levels from baseline will be evaluated.
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Timepoint [9]
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Baseline up to Day 56
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Secondary outcome [10]
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Part 3: Change From Baseline in Hepatitis B e Antigen (HBeAg) Levels
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Assessment method [10]
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The difference of HBeAg levels from baseline will be evaluated.
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Timepoint [10]
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Baseline up to Day 56
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Secondary outcome [11]
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Part 3: Relationship Between Plasma Concentration and Antiviral Activity
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Assessment method [11]
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The potential association between antiviral activity (like HBV DNA or HBsAg or HBeAg) and plasma concentration of JNJ-440 will be assessed.
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Timepoint [11]
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Up to Day 56
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Secondary outcome [12]
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Part 3: Relationship Between Plasma Concentration and Select AEs or Laboratory Changes
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Assessment method [12]
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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.
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Timepoint [12]
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Up to Day 56
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Secondary outcome [13]
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Part 3: Change From Baseline in HBV DNA (Antiviral Activity) in Chronic Hepatitis B (CHB) Participants with Sequence Variations in the HBV Genome
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Assessment method [13]
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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.
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Timepoint [13]
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Baseline up to Day 56
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Secondary outcome [14]
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Part 3: Number of Participants with Emergence of Treatment Associated Mutations in the HBV Genome
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Assessment method [14]
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Treatment induced emerging mutations will be assessed by comparing the HBV genome sequence obtained at baseline with sequences obtained post-baseline.
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Timepoint [14]
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Baseline up to Day 29
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Secondary outcome [15]
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Parts 1, 2, and 3: Relationship Between JNJ-440 Plasma Concentrations and Time-Matched Change from Baseline QTcF
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Assessment method [15]
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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.
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Timepoint [15]
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Approximately up to 18 weeks
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Eligibility
Key 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)
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Minimum age
18
Years
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Maximum age
55
Years
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Sex
Both males and females
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Can healthy volunteers participate?
Yes
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Key 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
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Study design
Purpose of the study
Other
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Other
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
26/03/2018
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
10/10/2019
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Sample size
Target
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Accrual to date
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Final
130
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Recruitment in Australia
Recruitment state(s)
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Recruitment outside Australia
Country [1]
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Korea, Republic of
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State/province [1]
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Seoul
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Country [2]
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Moldova, Republic of
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State/province [2]
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Chisnau
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Country [3]
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New Zealand
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State/province [3]
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Auckland
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Country [4]
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Thailand
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State/province [4]
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Bangkok
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Country [5]
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Thailand
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State/province [5]
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Khon Kaen
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Country [6]
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Ukraine
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State/province [6]
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Kapitanavka
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Alios Biopharma Inc.
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief 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).
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Trial website
https://clinicaltrials.gov/ct2/show/NCT03439488
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Jeysen Yogaratnam
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Address
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Alios Biopharma Inc.
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03439488
Download to PDF