A Single and Multiple Ascending Dose Study of JNJ-64457744

NCT05423106 | Terminated Phase 1

• 2 other identifiers: CR10920864457744HPB1001
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (7)

• Part 1, 2 and 3: Number of Participants With Serious Adverse Events (SAEs)

  SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; suspected transmission of any infectious agent via medicinal product; or any important medical events.

  Up to Week 8

• Part 1, 2 and 3: Number of Participants With SAEs by Severity

  SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; suspected transmission of any infectious agent via medicinal product; or any important medical events. Severity will be graded according to the Division of Division of Acquired Immunodeficiency Syndrome (DAIDS) grading table where Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Potentially Life-threatening.

  Up to Week 8

• Part 1, 2 and 3: Number of Participants With Clinical Laboratory Abnormalities

  Number of participants with clinical laboratory abnormalities (including hematology, biochemistry, coagulation, urinalysis) will be reported.

  Up to 8 weeks

• Part 1, 2 and 3: Number of Participants With Clinical Laboratory Abnormalities by Severity

  Number of participants with clinical laboratory abnormalities (including hematology, biochemistry, coagulation, urinalysis) will be reported. Severity will be graded according to the Division of AIDS (DAIDS) grading table where Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Potentially Life-threatening.

  Up to 8 weeks

• Part 1, 2 and 3: Number of Participants With Electrocardiograms (ECGs), Echocardiography, Vital Signs and Physical Examination Abnormalities

  Number of participants with abnormalities in ECGs, echocardiography, vital signs and physical examination will be reported.

  Up to Week 8

• Part 1, 2 and 3: Number of Participants With Electrocardiograms (ECGs), Echocardiography, Vital Signs and Physical Examination Abnormalities by Severity

  Number of participants with abnormalities in ECGs, echocardiography, vital signs and physical examination will be reported. Severity will be graded according to the Division of AIDS (DAIDS) grading table where Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Potentially Life-threatening.

  Up to 8 weeks

• Part 1, 2 and 3: Plasma concentration of JNJ-64457744

  Plasma concentration of JNJ-64457744 will be reported.

  Up to Week 8

Secondary Outcomes (4)

• Part 1: Plasma Concentration of JNJ-64457744: Within-Participant Analysis

  Up to 5 weeks

• Part 1: Plasma Concentration of JNJ-64457744 Under Fed and Fasted Condition

  Up to 5 weeks

• Part 1: Plasma Concentration of JNJ-64457744 Under Fasted Condition in Healthy Adult Asian Participants

  Up to 5 weeks

• Part 1: Plasma Concentration of JNJ-64457744 Formulation Under Fasted Conditions

  Up to 5 weeks

Study Arms (7)

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

EXPERIMENTAL

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.

Drug: JNJ-64457744; Drug: Placebo

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

EXPERIMENTAL

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.

Drug: JNJ-64457744

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

EXPERIMENTAL

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.

Drug: JNJ-64457744; Drug: Placebo

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

EXPERIMENTAL

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.

Drug: JNJ-64457744; Drug: Placebo

Part 1: JNJ-64457744 (Cohort K)

EXPERIMENTAL

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.

Drug: JNJ-64457744

Part 2 JNJ-64457744 or Placebo

EXPERIMENTAL

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.

Drug: JNJ-64457744; Drug: Placebo; Drug: Tenofovir Disoproxil Fumarate (TDF); Drug: Tenofovir Alafenamide (TAF); Drug: Entecavir (ETV)

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

EXPERIMENTAL

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

Drug: JNJ-64457744; Drug: Placebo

Interventions

JNJ-64457744 DRUG

JNJ-64457744 will be administered as oral solution.

Part 1: JNJ-64457744 (Cohorts G-H); Part 1: JNJ-64457744 or Placebo (Cohort I); Part 1: JNJ-64457744 or Placebo (Cohort J); Part 1: JNJ-64457744 or Placebo (Single Ascending Dose [SAD] Cohorts A-F); Part 2 JNJ-64457744 or Placebo; Part 3: JNJ-64457744 or Placebo (Multiple Ascending Doses [MADs])

Placebo DRUG

Placebo will be administered as an oral formulation.

Part 1: JNJ-64457744 or Placebo (Cohort I); Part 1: JNJ-64457744 or Placebo (Cohort J); Part 1: JNJ-64457744 or Placebo (Single Ascending Dose [SAD] Cohorts A-F); Part 2 JNJ-64457744 or Placebo; Part 3: JNJ-64457744 or Placebo (Multiple Ascending Doses [MADs])

Tenofovir Disoproxil Fumarate (TDF) DRUG

TDF tablet will be administered orally

Part 2 JNJ-64457744 or Placebo

Tenofovir Alafenamide (TAF) DRUG

TAF tablet will be administered orally.

Part 2 JNJ-64457744 or Placebo

Entecavir (ETV) DRUG

ETV tablet will be administered orally.

Part 2 JNJ-64457744 or Placebo

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

New Zealand Clinical Research

Grafton, 1010, New Zealand

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Tenofovir; tenofovir alafenamide; entecavir

Condition Hierarchy (Ancestors)

Hepatitis B; 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

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Janssen Research and Development, LLC Clinical Trial

  Janssen Research and Development LLC

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: June 6, 2022
• First Posted: June 21, 2022
• Study Start: July 4, 2022
• Primary Completion: March 14, 2023
• Study Completion: March 20, 2023
• Last Updated: February 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

NZ (1)