A Single and Multiple Ascending Dose Study of JNJ-64457744

Healthy Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05423106
• Other study ID #: CR109208
• Secondary ID: 64457744HPB1001
• Status: Terminated
• Phase: Phase 1
• Start date: July 4, 2022
• Est. completion date: March 20, 2023

Study information

• Verified date: June 2023
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 60
• Est. completion date: March 20, 2023
• Est. primary completion date: March 14, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Drug:
• JNJ-64457744
JNJ-64457744 will be administered as oral solution.
• Placebo
Placebo will be administered as an oral formulation.
• Tenofovir Disoproxil Fumarate (TDF)
TDF tablet will be administered orally
• Tenofovir Alafenamide (TAF)
TAF tablet will be administered orally.
• Entecavir (ETV)
ETV tablet will be administered orally.
• JNJ-64457744
JNJ-64457744 will be administered as oral tablet.

Locations

Country	Name	City	State
New Zealand	New Zealand Clinical Research	Grafton

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Part 1, 2 and 3: Plasma concentration of JNJ-64457744	Plasma concentration of JNJ-64457744 will be reported.	Up to Week 8
Secondary	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.	Up to 5 weeks
Secondary	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.	Up to 5 weeks
Secondary	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.	Up to 5 weeks
Secondary	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.	Up to 5 weeks