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

Browse trials for

• Hepatitis B, Chronic 954
• Hepatitis B 1,662

Keywords

• First in Human
• Healthy Volunteers
• Hepatitis B Virus
• JNJ-64530440

Hepatitis B, Chronic

954 studies on the registry are indexed under Hepatitis B, Chronic; 147 are open to participants now.

This study's enrollment of 130 is above the median of 100 across 692 interventional studies indexed under Hepatitis B, Chronic.

Lead sponsor

Alios Biopharma Inc. is the lead sponsor of 21 studies on the registry; none are open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 1 (20%) have results posted.

First submitted after Alios Biopharma Inc. became part of Johnson & Johnson.

Eligibility criteria

Study arms

• 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.

  Drug: JNJ-440 · Drug: Placebo

• 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.

  Drug: JNJ-440 · Drug: Placebo

• 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.

  Drug: JNJ-440 · Drug: Placebo

Interventions

• 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.

  Also known as: JNJ-64530440 or ALS-003440

• DrugPlacebo

  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

   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.

   Time frame: Approximately up to 8 weeks

2. 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.

   Time frame: Approximately up to 8 weeks

3. 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.

   Time frame: Approximately up to 8 weeks

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

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

   Time frame: Approximately up to 8 weeks

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

   Number of participants with Holter monitoring abnormalities will be reported.

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

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

   Number of participants with clinical laboratory abnormalities will be reported.

   Time frame: Approximately up to 8 weeks

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

   The Cmax is the maximum observed plasma concentration.

   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)

8. 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.

   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)

9. 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.

   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)

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

    The Cmax is the maximum observed plasma concentration.

    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])

11. 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).

    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])

12. 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.

    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])

Secondary outcomes

1. 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).

   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)

2. 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).

   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)

3. 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).

   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)

4. 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).

   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)

5. 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).

   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)

6. 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).

   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)

7. 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.

   Time frame: Baseline up to Day 56

8. 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.

   Time frame: Baseline up to Day 56

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

   The difference of HBsAg levels from baseline will be evaluated.

   Time frame: Baseline up to Day 56

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

    The difference of HBeAg levels from baseline will be evaluated.

    Time frame: Baseline up to Day 56

11. 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.

    Time frame: Up to Day 56

12. 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.

    Time frame: Up to Day 56

13. 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.

    Time frame: Baseline up to Day 56

14. 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.

    Time frame: Baseline up to Day 29

15. 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.

    Time frame: Approximately up to 18 weeks

Publications

• Kakuda TN, Yogaratnam JZ, Westland C, Gane EJ, Schwabe C, Vuong J, Patel M, Snoeys J, Talloen W, Lenz O, Fry J, Chanda S, van Remoortere P. Pharmacokinetics, safety and tolerability of single- and multiple-ascending doses of JNJ-64530440, a novel hepatitis B virus capsid assembly modulator, in healthy volunteers. Antivir Ther. 2021 Jan-Feb;26(1-2):13-24. doi: 10.1177/13596535211044331. Epub 2021 Sep 23. PubMed 35485346 ↗
• Gane EJ, Schwabe C, Berliba E, Tangkijvanich P, Jucov A, Ghicavii N, Verbinnen T, Lenz O, Talloen W, Kakuda TN, Westland C, Patel M, Yogaratnam JZ, Dragone L, Van Remoortere P. Safety, antiviral activity and pharmacokinetics of JNJ-64530440, a novel capsid assembly modulator, as 4 week monotherapy in treatment-naive patients with chronic hepatitis B virus infection. J Antimicrob Chemother. 2022 Mar 31;77(4):1102-1110. doi: 10.1093/jac/dkab491. PubMed 35040959 ↗