Clinical trial NCT05423106: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy
Hepatitis B, Chronic
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2022-06-21
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Part 1, 2 and 3: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: Up to Week 8
measure: Part 1, 2 and 3: Number of Participants With SAEs by Severity
timeFrame: Up to Week 8
measure: Part 1, 2 and 3: Number of Participants With Clinical Laboratory Abnormalities
timeFrame: Up to 8 weeks
measure: Part 1, 2 and 3: Number of Participants With Clinical Laboratory Abnormalities by Severity
timeFrame: Up to 8 weeks
measure: Part 1, 2 and 3: Number of Participants With Electrocardiograms (ECGs), Echocardiography, Vital Signs and Physical Examination Abnormalities
timeFrame: Up to Week 8
measure: Part 1, 2 and 3: Number of Participants With Electrocardiograms (ECGs), Echocardiography, Vital Signs and Physical Examination Abnormalities by Severity
timeFrame: Up to 8 weeks
measure: Part 1, 2 and 3: Plasma concentration of JNJ-64457744
timeFrame: Up to Week 8
Secondary outcomes:
measure: Part 1: Plasma Concentration of JNJ-64457744: Within-Participant Analysis
timeFrame: Up to 5 weeks
measure: Part 1: Plasma Concentration of JNJ-64457744 Under Fed and Fasted Condition
timeFrame: Up to 5 weeks
measure: Part 1: Plasma Concentration of JNJ-64457744 Under Fasted Condition in Healthy Adult Asian Participants
timeFrame: Up to 5 weeks
measure: Part 1: Plasma Concentration of JNJ-64457744 Formulation Under Fasted Conditions
timeFrame: Up to 5 weeks
Other outcomes:
Locations:
city: Grafton
country: New Zealand
facility: New Zealand Clinical Research
Study officials:
affiliation: Janssen Research and Development LLC
name: Janssen Research and Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: