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

NCT ID: NCT03439488

Last Updated: 2025-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-26
• Study Completion Date: 2019-10-10

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

JNJ-440

Intervention Type: 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.

Placebo

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

JNJ-440

Intervention Type: 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.

Placebo

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

JNJ-440

Intervention Type: 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.

Placebo

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

JNJ-64530440 or ALS-003440

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Alios Biopharma Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeysen Yogaratnam

Role: STUDY_DIRECTOR

Alios Biopharma Inc.

Locations

Republican Clinical Hospital

Chisnau, , Moldova

Auckland Clinical Services

Auckland, , New Zealand

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

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

Bangkok, , Thailand

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

Khon Kaen, , Thailand

Limited Liability Company "ARENSIA EXPLORATORY MEDICINE"

Kapitanavka, , Ukraine

Countries

Moldova; New Zealand; South Korea; Thailand; Ukraine

References

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.

Reference Type: DERIVED

PMID: 35485346 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35040959 (View on PubMed)

Other Identifiers

JNJ-440-1301

Identifier Type: OTHER

Identifier Source: secondary_id

2017-004657-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

JNJ-440-1301

Identifier Type: -

Identifier Source: org_study_id