Chronic Hepatitis B
Conditions
Keywords
First in Human, Healthy Volunteers, Hepatitis B Virus, JNJ-64530440
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).
Interventions
DRUGPlacebo
Matching placebo as oral tablets will be administered in Parts 1, 2 and 3.
DRUGJNJ-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.
Sponsors
Alios Biopharma Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Parts 1, 2, and 3: Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability | 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. |
| Parts 1, 2, and 3: Number of Participants With Clinically Significant Changes in Physical Examination (Body Weight Measurement and Skin Examination) | 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. |
| Parts 1, 2, and 3: Number of Participants With Clinically Significant Changes in Vital Signs | Approximately up to 8 weeks | Number of participants with clinically significant changes in the vital signs will be reported. |
| Parts 1, 2, and 3: Number of Participants With ECG Abnormalities | Approximately up to 8 weeks | Number of participants with electrocardiogram (ECG) abnormalities will be reported. |
| Parts 1, 2, and 3: Number of Participants With Holter Monitoring Abnormalities | Up to 24 hours post-dose on Day 1 | Number of participants with Holter monitoring abnormalities will be reported. |
| Parts 1, 2, and 3: Number of Participants With Clinical Laboratory Abnormalities | Approximately up to 8 weeks | Number of participants with clinical laboratory abnormalities will be reported. |
| Part 1: Maximum Observed Plasma Concentration (Cmax) | 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. |
| Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) | 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. |
| Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) | 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. |
| Part 3: Maximum Observed Plasma Concentration (Cmax) | 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. |
| Part 3: Observed Plasma Concentration From Time 0 to tau Hours Postdose (C[0-tau]) | 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). |
| Part 3: Area Under the Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) | 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
| Measure | Time frame | Description |
|---|---|---|
| Part 3: Change From Baseline in HBV DNA (Antiviral Activity) in Chronic Hepatitis B (CHB) Participants with Sequence Variations in the HBV Genome | 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. |
| Part 1: Ratio of Cmax Values Between Test and Reference Ratio (Cmax, test/reference) for Different Dosage Forms | 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). |
| Parts 1, 2, and 3: Relationship Between JNJ-440 Plasma Concentrations and Time-Matched Change from Baseline QTcF | 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. |
| Part 3: Number of Participants with Emergence of Treatment Associated Mutations in the HBV Genome | 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. |
| Part 1: Ratio of AUC(0-last) Values Between Test and Reference (Ratio AUC[0-last],test/reference) for Different Dosage Forms | 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). |
| Part 1: Ratio of AUC(0-infinity) Values Between Test and Reference (Ratio AUC[0-infinity], test/reference) for Different Dosage Forms | 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). |
| Part 1: Ratio of Cmax Values Between Fed and Fasted (Ratio Cmax, test/reference) Conditions | 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). |
| Part 1: Ratio of AUC(0-last) Values Between Fed and Fasted (Ratio AUC[0- last],test/reference) | 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). |
| Part 1: Ratio of AUC(0-infinity) Values Between Fed and Fasted (Ratio AUC[0-infinity], test/reference) | 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). |
| Part 3: Mean Change from Baseline in HBV DNA Levels | 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. |
| Part 3: Percentage of Participants with HBV DNA Levels and Undetectable HBV DNA | 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. |
| Part 3: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Baseline up to Day 56 | The difference of HBsAg levels from baseline will be evaluated. |
| Part 3: Change From Baseline in Hepatitis B e Antigen (HBeAg) Levels | Baseline up to Day 56 | The difference of HBeAg levels from baseline will be evaluated. |
| Part 3: Relationship Between Plasma Concentration and Antiviral Activity | 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. |
| Part 3: Relationship Between Plasma Concentration and Select AEs or Laboratory Changes | 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. |
Countries
Moldova, New Zealand, South Korea, Thailand, Ukraine
Outcome results
None listed