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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Placebo; Drug: JNJ-64417184

Study type: Interventional

Funder types: Industry

Identifiers

NCT03403348

JNJ-184-1401 (Other Identifier)

2017-004363-13 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 130 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

---

130 participants in 7 patient groups

Part 1: Single Ascending Dose (SAD)

Experimental group

Description:

Participants will be enrolled in 7 cohorts and receive one of the 7 corresponding SADs of JNJ-64417184, starting from 40 milligram (mg), or placebo in a fasted state. Dose escalation in the subsequent cohorts will depend on the human maximum observed plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) in previous cohorts.

Treatment:

Drug: JNJ-64417184

Drug: Placebo

Part 2A: Food Effect

Experimental group

Description:

Participants enrolled in cohort 4 of part 1 will roll-over in Part 2A and will receive a single oral dose (the same dose as received in Part 1) of JNJ-64417184 or placebo with a high-fat meal.

Treatment:

Drug: JNJ-64417184

Drug: Placebo

Part 2B: Relative Bioavailability (Optional)

Experimental group

Description:

Participants enrolled in cohorts 5, 6, 7 or any other optional cohorts of Part 1 will roll-over in Part 2B and will receive a single oral dose (the same dose as received in Part 1) of JNJ-64417184 or placebo under fasted state. Dosing may be changed from fasted to a fed state, depending on emerging pharmacokinetics (PK) data from Part 2A.

Treatment:

Drug: JNJ-64417184

Drug: Placebo

Part 3: Multiple Ascending Dose (MAD)

Experimental group

Description:

Participants will be enrolled in 3 cohorts and will receive one of the 3 corresponding MADs of JNJ-64417184 or placebo, dosed once daily for 7 days. There will be 3 optional cohorts and participants in these cohorts will follow 7- to 14-day dosing schedule. Dosing will either occur in the fasted or the fed state, depending on the outcome of Part 2A. Dose selection and dose escalation in the MAD cohorts will depend on the observed human Cmax and AUC in previous (SAD) cohorts. Additional cohorts may be evaluated at the discretion of the Sponsor and the Principal Investigator (PI).

Treatment:

Drug: JNJ-64417184

Drug: Placebo

Part 4: Human RSV Challenge (Proof-of-Concept Study Part)

Experimental group

Description:

Based on emerging PK and safety data from Part 3 (MAD), the participants inoculated with respiratory syncytial virus (RSV) -A Memphis 37b and confirmed positive by polymerase chain reaction (PCR) will either receive JNJ-64417184 or placebo once daily OR receive JNJ-64417184 (low dose), JNJ-64417184 (high dose) or placebo once daily.

Treatment:

Drug: JNJ-64417184

Drug: Placebo

Part 5: SAD/Japanese

Experimental group

Description:

Participants of Japanese descent will be enrolled in 3 cohorts and will receive one of the corresponding SADs of JNJ-64417184 or placebo in a fasted state. Dosing may be changed from fasted to a fed state, depending on emerging PK data from Part 2A. The starting dose and formulation will be selected based on the outcome of Parts 1 and 2. Dose escalation in the subsequent cohorts will depend on the observed human Cmax and AUC in previous cohorts.

Treatment:

Drug: JNJ-64417184

Drug: Placebo

Part 6: MAD/Japanese (Optional)

Experimental group

Description:

Participants of Japanese descent may be enrolled in 3 cohorts and will receive one of the corresponding MADs of JNJ-64417184 or placebo, dosed once daily for 7 to 14 days. Dosing will either occur in the fasted or the fed state, depending on the outcome of Part 2A. Dose selection and dose escalation in the MAD cohorts will depend on the observed human Cmax and AUC in previous (Parts 1, 2, 3, and 5) cohorts.

Treatment:

Drug: JNJ-64417184

Drug: Placebo