A Single and Multiple Ascending Dose Study of JNJ-64457744

Janssen (J&J Innovative Medicine)

Status and phase

Terminated

Phase 1

Conditions

Healthy

Hepatitis B, Chronic

Treatments

Drug: JNJ-64457744

Drug: Entecavir (ETV)

Drug: Placebo

Drug: Tenofovir Alafenamide (TAF)

Drug: Tenofovir Disoproxil Fumarate (TDF)

Study type

Interventional

Funder types

Industry

Identifiers

NCT05423106

64457744HPB1001 (Other Identifier)

CR109208

Details and patient eligibility

About

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).

Enrollment

60 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Sequential Assignment

Masking

Double Blind

60 participants in 7 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: JNJ-64457744

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

Experimental group

Description:

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.

Treatment:

Drug: JNJ-64457744

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

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: JNJ-64457744

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

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: JNJ-64457744

Part 1: JNJ-64457744 (Cohort K)

Experimental group

Description:

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.

Treatment:

Drug: JNJ-64457744

Part 2 JNJ-64457744 or Placebo

Experimental group

Description:

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.

Treatment:

Drug: Tenofovir Disoproxil Fumarate (TDF)

Drug: Tenofovir Alafenamide (TAF)

Drug: Entecavir (ETV)

Drug: Placebo

Drug: JNJ-64457744

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

Experimental group

Description:

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

Treatment:

Drug: Placebo