A Single and Multiple Ascending Dose Study of JNJ-64457744

NCT ID: NCT05423106

Last Updated: 2025-02-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-04
• Study Completion Date: 2023-03-20

Brief Summary

The purpose of the study is to evaluate the safety and tolerability of: single ascending dose (SAD) and multiple ascending dose (MAD) administration of JNJ-64457744, administered to healthy adult participants (Part 1 and Part 3), including a cohort of Asian participants (Part 1); and after single dose administration of JNJ-64457744 to chronic hepatitis B (CHB) participants who are virologically suppressed on nucleos(t)ide analog (NA) treatment (tenofovir disoproxil fumarate [TDF], tenofovir alafenamide [TAF], or entecavir [ETV]) (Part 2).

Conditions

Healthy; Hepatitis B, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part 1: JNJ-64457744 or Placebo (Single Ascending Dose [SAD] Cohorts A-F)

Non-Asian healthy participants will receive a SAD of either JNJ-64457744 or matching placebo as an oral formulation under fasted conditions on Day 1. Cohort F will be optional.

Group Type: EXPERIMENTAL

JNJ-64457744

Intervention Type: DRUG

JNJ-64457744 will be administered as oral solution.

Placebo

Intervention Type: DRUG

Placebo will be administered as an oral formulation.

Part 1: JNJ-64457744 (Cohorts G-H)

Non-Asian healthy participants will receive 3 single doses of JNJ-64457744 as an oral formulation in 3 intervention periods (to assess inter-subject PK-PD) matching the doses evaluated in Cohorts A, C and E for Cohort G and Cohorts B, D and F for Cohort H, under fasted conditions on Day 1. Cohort H will be optional for Intervention period 3.

Group Type: EXPERIMENTAL

JNJ-64457744

Intervention Type: DRUG

JNJ-64457744 will be administered as oral solution.

Part 1: JNJ-64457744 or Placebo (Cohort I)

Non-Asian healthy participants who previously received study intervention under fasted conditions will receive either JNJ-64457744 or matching placebo as an oral formulation (depending upon what was administered previously in Cohorts A to F) under fed conditions on Day 1.

Group Type: EXPERIMENTAL

JNJ-64457744

Intervention Type: DRUG

JNJ-64457744 will be administered as oral solution.

Placebo

Intervention Type: DRUG

Placebo will be administered as an oral formulation.

Part 1: JNJ-64457744 or Placebo (Cohort J)

Asian healthy participants will receive a single dose at one single dose level of either JNJ-64457744 or matching placebo, as an oral formulation, under fasted conditions on Day 1.

Group Type: EXPERIMENTAL

JNJ-64457744

Intervention Type: DRUG

JNJ-64457744 will be administered as oral solution.

Placebo

Intervention Type: DRUG

Placebo will be administered as an oral formulation.

Part 1: JNJ-64457744 (Cohort K)

Optional Cohort K: Non-Asian healthy participants will receive an oral formulation of JNJ-64457744 in the first intervention period and will cross over to receive the other formulation during the second intervention period, under fasted conditions on Day 1.

Group Type: EXPERIMENTAL

JNJ-64457744

Intervention Type: DRUG

JNJ-64457744 will be administered as oral tablet.

Part 2 JNJ-64457744 or Placebo

Chronic hepatitis B participants who are virologically suppressed on nucleos(t)ide analog (NA) treatment (tenofovir disoproxil fumarate \[TDF\], tenofovir alafenamide \[TAF\] and entecavir \[ETV\]) will receive a single dose at one single dose level of either JNJ-64457744 or matching placebo as an oral formulation, under fasted condition on Day 1.

Group Type: EXPERIMENTAL

JNJ-64457744

Intervention Type: DRUG

JNJ-64457744 will be administered as oral solution.

Placebo

Intervention Type: DRUG

Placebo will be administered as an oral formulation.

Tenofovir Disoproxil Fumarate (TDF)

Intervention Type: DRUG

TDF tablet will be administered orally

Tenofovir Alafenamide (TAF)

Intervention Type: DRUG

TAF tablet will be administered orally.

Entecavir (ETV)

Intervention Type: DRUG

ETV tablet will be administered orally.

Part 3: JNJ-64457744 or Placebo (Multiple Ascending Doses [MADs])

Participants will receive MADs of either JNJ-64457744 or matching placebo once weekly under fasted conditions as an oral formulation.

Group Type: EXPERIMENTAL

JNJ-64457744

Intervention Type: DRUG

JNJ-64457744 will be administered as oral solution.

Placebo

Intervention Type: DRUG

Placebo will be administered as an oral formulation.

Interventions

JNJ-64457744

JNJ-64457744 will be administered as oral solution.

Intervention Type: DRUG

Placebo

Placebo will be administered as an oral formulation.

Intervention Type: DRUG

Tenofovir Disoproxil Fumarate (TDF)

TDF tablet will be administered orally

Intervention Type: DRUG

Tenofovir Alafenamide (TAF)

TAF tablet will be administered orally.

Intervention Type: DRUG

Entecavir (ETV)

ETV tablet will be administered orally.

Intervention Type: DRUG

JNJ-64457744

JNJ-64457744 will be administered as oral tablet.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Normal left ventricular heart function as defined as left ventricular ejection fraction (LVEF) greater than or equal to (>=) 5 percent (%), as assessed by 2 dimension electrocardiogram (2DECHO) at screening
• All women must have a negative urine pregnancy test at screening and Day -1 (of each intervention period, if applicable)
• A woman must not be of childbearing potential
• Part 1 and 3: Must have an estimated creatinine clearance greater than (>) 80 milliliter (mL) per minute at screening, calculated by the modification of diet in renal disease (MDRD) formula
• Part 2: Must have chronic HBV infection. HBV infection must be documented by serum HBsAg positivity at screening
• Must be fully vaccinated against coronavirus disease 2019 (COVID-19) at least 2 weeks prior to screening calculated by the modification of diet in renal disease (MDRD) formula
• Participants in Cohorts A-I and K in Part 1 must not have maternal and paternal parents and/or grandparents of Asian ethnicity (that is, China, Japan, Korea as confirmed by interview) Participants in Cohort J must have maternal and paternal parents and grandparents of Asian ethnicity (that is, China, Japan, Korea as confirmed by interview)

Exclusion Criteria

• History of cardiac arrhythmias (example, extrasystole, tachycardia at rest), history of risk factors for Torsades 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 second and third degree heart block or right bundle branch block is also exclusionary
• Participants with abnormal sinus rhythm (heart rate less than [<] 45 or > 100 beats per minute [bpm]), QT corrected for heart rate according to Fridericia's formula (QTcF) > 450 milliseconds (ms) for male participants and > 470 ms for female participants, QRS >= 120 ms, PR interval >220 ms, abnormal conduction, or any other clinically significant abnormalities on a 12-lead ECG at screening
• Family history of inherited mitochondrial disorders such as inherited mitochondrial myopathy, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome
• Known allergies, hypersensitivity, or intolerance to JNJ-64457744 or its excipients
• History of clinically significant drug allergy such as, but not limited to, sulfonamides and penicillins, or drug allergy witnessed in previous studies with experimental drugs

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

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research and Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research and Development LLC

Locations

New Zealand Clinical Research

Grafton, , New Zealand

Countries

New Zealand

Other Identifiers

64457744HPB1001

Identifier Type: OTHER

Identifier Source: secondary_id

CR109208

Identifier Type: -

Identifier Source: org_study_id