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Completed

NCT Number: NCT03439488

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

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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Key information

Conditions

Chronic Hepatitis B Blood-Borne Infections Chronic Disease Communicable Diseases DNA Virus Infections Digestive System Diseases Disease Attributes Hepadnaviridae Infections Hepatitis Hepatitis B Hepatitis B, Chronic Hepatitis, Chronic Hepatitis, Viral, Human Infections Liver Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Virus Diseases

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Republican Clinical Hospital, Chisnau, Moldova

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

JNJ-440

Drug

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.

Other names: JNJ-64530440 or ALS-003440

Placebo

Drug

Matching placebo as oral tablets will be administered in Parts 1, 2 and 3.

Primary outcomes

  1. Parts 1, 2, and 3: Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability

    Time frame: Approximately up to 8 weeks

    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.

  2. Parts 1, 2, and 3: Number of Participants With Clinically Significant Changes in Physical Examination (Body Weight Measurement and Skin Examination)

    Time frame: Approximately up to 8 weeks

    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.

  3. Parts 1, 2, and 3: Number of Participants With Clinically Significant Changes in Vital Signs

    Time frame: Approximately up to 8 weeks

    Number of participants with clinically significant changes in the vital signs will be reported.

  4. Parts 1, 2, and 3: Number of Participants With ECG Abnormalities

    Time frame: Approximately up to 8 weeks

    Number of participants with electrocardiogram (ECG) abnormalities will be reported.

  5. Parts 1, 2, and 3: Number of Participants With Holter Monitoring Abnormalities

    Time frame: Up to 24 hours post-dose on Day 1

    Number of participants with Holter monitoring abnormalities will be reported.

  6. Parts 1, 2, and 3: Number of Participants With Clinical Laboratory Abnormalities

    Time frame: Approximately up to 8 weeks

    Number of participants with clinical laboratory abnormalities will be reported.

  7. Part 1: Maximum Observed Plasma Concentration (Cmax)

    Time frame: 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)

    The Cmax is the maximum observed plasma concentration.

  8. Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])

    Time frame: 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)

    The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.

  9. Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])

    Time frame: 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)

    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.

  10. Part 3: Maximum Observed Plasma Concentration (Cmax)

    Time frame: 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])

    The Cmax is the maximum observed plasma concentration.

  11. Part 3: Observed Plasma Concentration From Time 0 to tau Hours Postdose (C[0-tau])

    Time frame: 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])

    C(0-tau) is defined as the observed plasma concentration from time 0 to tau hours postdose (tau = dosing interval).

  12. Part 3: Area Under the Curve From Time Zero to End of Dosing Interval (AUC[0-tau])

    Time frame: 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])

    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.

Secondary outcomes

  1. Part 1: Ratio of Cmax Values Between Test and Reference Ratio (Cmax, test/reference) for Different Dosage Forms

    Time frame: 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)

    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).

  2. Part 1: Ratio of AUC(0-last) Values Between Test and Reference (Ratio AUC[0-last],test/reference) for Different Dosage Forms

    Time frame: 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)

    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).

  3. Part 1: Ratio of AUC(0-infinity) Values Between Test and Reference (Ratio AUC[0-infinity], test/reference) for Different Dosage Forms

    Time frame: 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)

    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).

  4. Part 1: Ratio of Cmax Values Between Fed and Fasted (Ratio Cmax, test/reference) Conditions

    Time frame: 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)

    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).

  5. Part 1: Ratio of AUC(0-last) Values Between Fed and Fasted (Ratio AUC[0- last],test/reference)

    Time frame: 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)

    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).

  6. Part 1: Ratio of AUC(0-infinity) Values Between Fed and Fasted (Ratio AUC[0-infinity], test/reference)

    Time frame: 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)

    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).

  7. Part 3: Mean Change from Baseline in HBV DNA Levels

    Time frame: Baseline up to Day 56

    Changes of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels as assessed by mean change from baseline in HBV DNA will be evaluated.

  8. Part 3: Percentage of Participants with HBV DNA Levels and Undetectable HBV DNA

    Time frame: Baseline up to Day 56

    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.

  9. Part 3: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels

    Time frame: Baseline up to Day 56

    The difference of HBsAg levels from baseline will be evaluated.

  10. Part 3: Change From Baseline in Hepatitis B e Antigen (HBeAg) Levels

    Time frame: Baseline up to Day 56

    The difference of HBeAg levels from baseline will be evaluated.

  11. Part 3: Relationship Between Plasma Concentration and Antiviral Activity

    Time frame: Up to Day 56

    The potential association between antiviral activity (like HBV DNA or HBsAg or HBeAg) and plasma concentration of JNJ-440 will be assessed.

  12. Part 3: Relationship Between Plasma Concentration and Select AEs or Laboratory Changes

    Time frame: Up to Day 56

    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.

  13. Part 3: Change From Baseline in HBV DNA (Antiviral Activity) in Chronic Hepatitis B (CHB) Participants with Sequence Variations in the HBV Genome

    Time frame: Baseline up to Day 56

    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.

  14. Part 3: Number of Participants with Emergence of Treatment Associated Mutations in the HBV Genome

    Time frame: Baseline up to Day 29

    Treatment induced emerging mutations will be assessed by comparing the HBV genome sequence obtained at baseline with sequences obtained post-baseline.

  15. Parts 1, 2, and 3: Relationship Between JNJ-440 Plasma Concentrations and Time-Matched Change from Baseline QTcF

    Time frame: Approximately up to 18 weeks

    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.

Sponsors and collaborators

Lead sponsor

Alios Biopharma Inc.

Industry

Registry information

Official study 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)

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Feb 20, 2018
Registry last updated
Feb 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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