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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05423106




Registration number
NCT05423106
Ethics application status
Date submitted
6/06/2022
Date registered
21/06/2022
Date last updated
8/06/2023

Titles & IDs
Public title
A Single and Multiple Ascending Dose Study of JNJ-64457744
Scientific 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
Secondary ID [1] 0 0
64457744HPB1001
Secondary ID [2] 0 0
CR109208
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy 0 0
Hepatitis B, Chronic 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - JNJ-64457744
Treatment: Drugs - Placebo
Treatment: Drugs - Tenofovir Disoproxil Fumarate (TDF)
Treatment: Drugs - Tenofovir Alafenamide (TAF)
Treatment: Drugs - Entecavir (ETV)
Treatment: Drugs - JNJ-64457744

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

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

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

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

Experimental: Part 1: JNJ-64457744 (Cohort K) - 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.

Experimental: Part 2 JNJ-64457744 or Placebo - 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.

Experimental: Part 3: JNJ-64457744 or Placebo (Multiple Ascending Doses [MADs]) - Participants will receive MADs of either JNJ-64457744 or matching placebo once weekly under fasted conditions as an oral formulation.


Treatment: Drugs: JNJ-64457744
JNJ-64457744 will be administered as oral solution.

Treatment: Drugs: Placebo
Placebo will be administered as an oral formulation.

Treatment: Drugs: Tenofovir Disoproxil Fumarate (TDF)
TDF tablet will be administered orally

Treatment: Drugs: Tenofovir Alafenamide (TAF)
TAF tablet will be administered orally.

Treatment: Drugs: Entecavir (ETV)
ETV tablet will be administered orally.

Treatment: Drugs: JNJ-64457744
JNJ-64457744 will be administered as oral tablet.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1, 2 and 3: Number of Participants With Serious Adverse Events (SAEs)
Timepoint [1] 0 0
Up to Week 8
Primary outcome [2] 0 0
Part 1, 2 and 3: Number of Participants With SAEs by Severity
Timepoint [2] 0 0
Up to Week 8
Primary outcome [3] 0 0
Part 1, 2 and 3: Number of Participants With Clinical Laboratory Abnormalities
Timepoint [3] 0 0
Up to 8 weeks
Primary outcome [4] 0 0
Part 1, 2 and 3: Number of Participants With Clinical Laboratory Abnormalities by Severity
Timepoint [4] 0 0
Up to 8 weeks
Primary outcome [5] 0 0
Part 1, 2 and 3: Number of Participants With Electrocardiograms (ECGs), Echocardiography, Vital Signs and Physical Examination Abnormalities
Timepoint [5] 0 0
Up to Week 8
Primary outcome [6] 0 0
Part 1, 2 and 3: Number of Participants With Electrocardiograms (ECGs), Echocardiography, Vital Signs and Physical Examination Abnormalities by Severity
Timepoint [6] 0 0
Up to 8 weeks
Primary outcome [7] 0 0
Part 1, 2 and 3: Plasma concentration of JNJ-64457744
Timepoint [7] 0 0
Up to Week 8
Secondary outcome [1] 0 0
Part 1: Plasma Concentration of JNJ-64457744: Within-Participant Analysis
Timepoint [1] 0 0
Up to 5 weeks
Secondary outcome [2] 0 0
Part 1: Plasma Concentration of JNJ-64457744 Under Fed and Fasted Condition
Timepoint [2] 0 0
Up to 5 weeks
Secondary outcome [3] 0 0
Part 1: Plasma Concentration of JNJ-64457744 Under Fasted Condition in Healthy Adult Asian Participants
Timepoint [3] 0 0
Up to 5 weeks
Secondary outcome [4] 0 0
Part 1: Plasma Concentration of JNJ-64457744 Formulation Under Fasted Conditions
Timepoint [4] 0 0
Up to 5 weeks

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/07/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
20/03/2023
Sample size
Target
Accrual to date
Final
60
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Grafton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT05423106
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research and Development, LLC Clinical Trial
Address 0 0
Janssen Research and Development LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05423106