Clinical trial NCT03403348: A First-In-Human Study of Orally Administered JNJ-64417184 to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses, and the Antiviral Activity of Multiple Doses in a Respiratory Syncytial Virus (RSV) Challenge Study in Healthy Participants
Official title: A Randomized, Double-blind, Placebo-controlled, First-in-human, 6-Part Study of Orally Administered JNJ-64417184 to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses, and the Antiviral Activity of Multiple Doses in a Respiratory Syncytial Virus (RSV) Challenge Study in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen BioPharma, Inc.
Sponsor class: INDUSTRY
First posted: 2018-01-18
Enrollment: 130
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 and multiple oral doses of JNJ-64417184 administered to healthy participants and the antiviral effect of multiple oral doses of JNJ-64417184 compared to placebo in participants infected through inoculation with respiratory syncytial virus (RSV)-A Memphis 37b (Part 4).


Eligibility criteria: Inclusion Criteria:

* Participant has provided written consent
* In the Investigator's opinion, the participant is able to understand and comply with protocol requirements, instructions, and protocol-stated restrictions and is likely to complete the study as planned
* Participant is in good health as deemed by the Investigator, based on the findings of a medical evaluation including medical history, physical examination, laboratory tests, and electrocardiogram (ECG). In case of an out-of-range clinical laboratory test, vital sign, or ECG value that will determine a participant's eligibility, a retest can be done. Results of this retest must be available prior to the first administration of the study drugs (Parts 1, 3, 5, and 6) or prior to inoculation (Part 4). The result of the retest will be considered for participant eligibility
* Body mass index (BMI) of 18 to 30 kilogram per meter square (kg/m\^2) (inclusive), minimum weight of 50 kilogram (kg)
* A female participant is eligible to participate in this study if she is of non childbearing potential defined as either (i) premenopausal with a documented tubal ligation, bilateral oophorectomy, or hysterectomy; or (ii) postmenopausal defined by 12 months of spontaneous amenorrhea and follicle-stimulating hormone level within the laboratory's reference range for postmenopausal females. A postmenopausal female who is receiving hormone replacement therapy and who is willing to discontinue hormone therapy from 28 days before study drug dosing (Parts 1, 3, 5, and 6) or before inoculation (Part 4), and for the entire duration of the study, may be eligible for study participation. A male participant is eligible to participate in this study if (i) he is either surgically sterile or, (ii) in case of having a female partner of childbearing potential, the male participant and partner are practicing and willing to continue to practice highly effective forms of birth control until 90 days after the end of the study. Irrespective of the partner's form of birth control, a male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person

Exclusion Criteria:

* Clinically significant cardiovascular, respiratory, renal, gastrointestinal, hematologic, neurologic, endocrinologic, oncologic, ophthalmologic, musculoskeletal, psychiatric or any other uncontrolled medical illness
* Positive human immunodeficiency virus (HIV), active hepatitis A virus (HAV), hepatitis B virus (HBV), or hepatitis C virus (HCV) test
* Creatinine clearance less than (\<) 60 milliliter per minute (mL/min) (Cockcroft-Gault)
* Drug allergy such as, but not limited to, allergy to penicillins, including allergies experienced in previous studies with experimental drugs
* Any condition that, in the opinion of the Investigator, would compromise the study or the well-being of the participant or prevent the participant from meeting the study requirements

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: Approximately up to 8 months
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Approximately up to 8 months
measure: Number of Participants With Clinically Significant Changes in Vital Signs
timeFrame: Approximately up to 8 months
measure: Number of Participants With Clinically Significant Changes in Physical Examination Findings
timeFrame: Approximately up to 8 months
measure: Number of Participants With ECG Abnormalities
timeFrame: Approximately up to 8 months
measure: Change From Baseline in QT Interval Corrected According to Fridericia's Formula (QTcF) (Parts 1 and 3)
timeFrame: Baseline up to Day 31
measure: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Absolute as Measured by Spirometry (Part 4)
timeFrame: Baseline up to Day 31
measure: Change From Baseline in Forced Vital Capacity (FVC) Absolute as Measured by Spirometry (Part 4)
timeFrame: Baseline up to Day 31
measure: Change From Baseline in Percent-Predicted FEV1 (Part 4)
timeFrame: Baseline up to Day 31
measure: Change From Baseline in Percent-Predicted FVC (Part 4)
timeFrame: Baseline up to Day 31
measure: Area Under the Concentration-Time Curve Between Time of First Administration and Dosing Day 7 (AUC[0-Dosing Day 7]) of RSV-A Memphis 37b Viral Load in Participants Infected Through Inoculation With This Viral Strain (Part 4)
timeFrame: Up to Day 7
Secondary outcomes:
measure: JNJ-64417184 Plasma Concentrations
timeFrame: Approximately up to 67 days
measure: JNJ-64417184 Urine Concentrations
timeFrame: Approximately up to 67 days
measure: Corrected QT Interval (QTc) Duration (Parts 1 and 3)
timeFrame: Up to Day 2 (Part 1); Up to Day 8 (Part 3)
measure: AUC(0-Dosing Day 7) of RSV Viral Load From Treatment Onset (Part 4)
timeFrame: Up to Day 7
measure: Time to Non-Detectability of RSV (Part 4)
timeFrame: Up to Day 31
measure: Peak RSV Viral Load by Dosing Day (Part 4)
timeFrame: Up to Day 31
measure: AUC(0-Dosing Day 7) of Total RSV Symptoms From Treatment Onset
timeFrame: Up to Day 7
measure: Total Weight of Mucus (Part 4)
timeFrame: Up to Day 12
measure: Change From Baseline in the RSV L Protein-Encoding Gene Sequence After Treatment (Part 4)
timeFrame: Baseline up to Day 11
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: hVIVO Services Limited
city: London
country: United Kingdom
facility: Hammersmith Medicines Research Ltd
Study officials:
affiliation: Janssen BioPharma, Inc.
name: Janssen Biopharma, Inc. Clinical Trial
role: STUDY_DIRECTOR
References: