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

NCT03439488 | Completed Phase 1 FDA Drug

• 2 other identifiers: JNJ-440-13012017-004657-17
• Study Type: interventional
• Target: 130
• Locations: 5 countries
• Sites: 7

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).

Conditions

Chronic Hepatitis B

Keywords

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

Outcome Measures

Primary Outcomes (12)

• 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

• 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

• 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

• 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

• 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

• 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

• 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)

• 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)

• 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)

• 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])

• 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])

• 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 Outcomes (15)

• 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)

• 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)

• 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)

• 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)

• 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)

Study Arms (3)

Part 1 (Healthy Participants): Single Ascending Dose (SAD)

EXPERIMENTAL

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

Part 2 (Healthy Participants): Multiple Ascending Dose (MAD)

EXPERIMENTAL

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

Part 3 (Chronic Hepatitis B [CHB] Participants): MAD

EXPERIMENTAL

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

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.

Also known as: JNJ-64530440 or ALS-003440

Part 1 (Healthy Participants): Single Ascending Dose (SAD); Part 2 (Healthy Participants): Multiple Ascending Dose (MAD); Part 3 (Chronic Hepatitis B [CHB] Participants): MAD

Placebo DRUG

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

Part 1 (Healthy Participants): Single Ascending Dose (SAD); Part 2 (Healthy Participants): Multiple Ascending Dose (MAD); Part 3 (Chronic Hepatitis B [CHB] Participants): MAD

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• Participant with positivity of anti-HBs antibodies
• Participants with current hepatitis D virus (HDV) infection (confirmed by HDV antibody) at screening

Sponsors & Collaborators

• Alios Biopharma Inc.: lead

Study Sites (7)

Republican Clinical Hospital

Chisnau, Moldova

Location

Auckland Clinical Services

Auckland, 8963, New Zealand

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Location

Research Unit of Hepatitis and Liver Cancer, Department.Biochemistry, Faculty of Medicine King Chulalongkorn Memorial Hospital

Bangkok, Thailand

Location

Srinagarind Hospital Department of Gastroenterology, Faculty of Medicine, Khon Kaen University

Khon Kaen, 40002, Thailand

Location

Limited Liability Company "ARENSIA EXPLORATORY MEDICINE"

Kapitanavka, 08112, Ukraine

Location

Related Publications (2)

• 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.

  PMID: 35485346 DERIVED

• 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.

  PMID: 35040959 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic; Hepatitis B

Condition Hierarchy (Ancestors)

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

Study Officials

• Jeysen Yogaratnam

  Alios Biopharma Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2018
• First Posted: February 20, 2018
• Study Start: March 26, 2018
• Primary Completion: October 10, 2019
• Study Completion: October 10, 2019
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

UA (1); TH (2); NZ (1); MO (1); KR (2)