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A Single and Multiple Ascending Dose Study of JNJ-64457744

Primary Purpose

Healthy, Hepatitis B, Chronic

Status

Terminated

Phase

Phase 1

Locations

New Zealand

Study Type

Interventional

Intervention

JNJ-64457744

Placebo

Tenofovir Disoproxil Fumarate (TDF)

Tenofovir Alafenamide (TAF)

Entecavir (ETV)

JNJ-64457744

About this trial

This is an interventional treatment trial for Healthy

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts 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

Sites / Locations

New Zealand Clinical Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Arm Label

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

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 (Cohort K)

Part 2 JNJ-64457744 or Placebo

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

Arm 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.

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.

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.

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.

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.

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.

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

Outcomes

Primary Outcome Measures

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

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.

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.

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.

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.

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.

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

Plasma concentration of JNJ-64457744 will be reported.

Secondary Outcome Measures

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

Plasma concentration of JNJ-64457744 assessed within-participant after administration of 3 different single doses under fasted conditions will be reported.

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

Plasma Concentration of JNJ-64457744 under fed and fasted conditions will be reported.

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

Plasma concentration of JNJ-64457744 under fasted conditions in healthy adult Asian participants will be reported.

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

Plasma Concentration of JNJ-64457744 formulation as compared with an oral solution formulation under fasted conditions will be reported.

Full Information

NCT ID

NCT05423106

First Posted

June 6, 2022

Last Updated

June 7, 2023

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT05423106

Brief Title

A Single and Multiple Ascending Dose Study of JNJ-64457744

Official Title

A Phase 1, Blinded, Randomized, Placebo-controlled, First-in-human Study of Orally Administered JNJ-64457744 to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Single and Multiple Ascending Doses

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Terminated

Why Stopped

Strategic business decision, not due to safety concerns

Study Start Date

July 4, 2022 (Actual)

Primary Completion Date

March 14, 2023 (Actual)

Study Completion Date

March 20, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Healthy, Hepatitis B, Chronic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm 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.

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm 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.

Arm Title

Part 1: JNJ-64457744 (Cohort K)

Arm Type

Experimental

Arm Description

Arm Title

Part 2 JNJ-64457744 or Placebo

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

JNJ-64457744

Intervention Description

JNJ-64457744 will be administered as oral solution.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo will be administered as an oral formulation.

Intervention Type

Drug

Intervention Name(s)

Tenofovir Disoproxil Fumarate (TDF)

Intervention Description

TDF tablet will be administered orally

Intervention Type

Drug

Intervention Name(s)

Tenofovir Alafenamide (TAF)

Intervention Description

TAF tablet will be administered orally.

Intervention Type

Drug

Intervention Name(s)

Entecavir (ETV)

Intervention Description

ETV tablet will be administered orally.

Intervention Type

Drug

Intervention Name(s)

JNJ-64457744

Intervention Description

JNJ-64457744 will be administered as oral tablet.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Up to Week 8

Title

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

Description

Time Frame

Up to Week 8

Title

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

Description

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

Time Frame

Up to 8 weeks

Title

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

Description

Time Frame

Up to 8 weeks

Title

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

Description

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

Time Frame

Up to Week 8

Title

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

Description

Time Frame

Up to 8 weeks

Title

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

Description

Plasma concentration of JNJ-64457744 will be reported.

Time Frame

Up to Week 8

Secondary Outcome Measure Information:

Title

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

Description

Plasma concentration of JNJ-64457744 assessed within-participant after administration of 3 different single doses under fasted conditions will be reported.

Time Frame

Up to 5 weeks

Title

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

Description

Plasma Concentration of JNJ-64457744 under fed and fasted conditions will be reported.

Time Frame

Up to 5 weeks

Title

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

Description

Plasma concentration of JNJ-64457744 under fasted conditions in healthy adult Asian participants will be reported.

Time Frame

Up to 5 weeks

Title

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

Description

Plasma Concentration of JNJ-64457744 formulation as compared with an oral solution formulation under fasted conditions will be reported.

Time Frame

Up to 5 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Research and Development, LLC Clinical Trial

Organizational Affiliation

Janssen Research and Development LLC

Official's Role

Study Director

Facility Information:

Facility Name

New Zealand Clinical Research

City

Grafton

ZIP/Postal Code

1010

Country

New Zealand

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

IPD Sharing URL

https://www.janssen.com/clinical-trials/transparency

Learn more about this trial

A Single and Multiple Ascending Dose Study of JNJ-64457744

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