A Study of JNJ-64281802 in Participants With Confirmed Dengue Fever

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the antiviral activity of JNJ-64281802 versus placebo in terms of reduction of dengue virus (DENV) ribonucleic acid (RNA) in primary DENV infection.

Official Title
-----------------
A Phase 2a, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Antiviral Activity, Safety and Tolerability, and Pharmacokinetics of JNJ-64281802 in Participants With Confirmed Dengue Fever

Conditions
-----------------
Dengue

Intervention / Treatment
-----------------
* Drug: JNJ-64281802
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant with a referral note/documentation from a health care facility or practitioner indicating non-structural 1 protein (NS1) positive for dengue virus (DENV), positive NS1 rapid test at pre-screening during an ambulatory visit, or participant who tests NS1 positive at the site Participant reported a fever with an onset within the last 48 hours A woman of childbearing potential must have a negative serum pregnancy test at screening A woman must be: a. not of childbearing potential, b. of childbearing potential and practicing a highly effective, preferably user-independent method of contraception (failure rate of less than [<] 1% per year when used consistently and correctly) and agrees to remain on a highly effective method while receiving study intervention and until at least 90 days after last dose- the end of relevant systemic exposure A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose of study intervention Exclusion Criteria: Participant with any clinical signs and symptoms for severe dengue according to the world health organization (WHO) criteria (such as severe plasma leakage leading to dengue shock syndrome [DSS], fluid accumulation with respiratory distress, severe bleeding, sever organ involvement) Use of any cytochrome 3A4 (CYP3A4) inducers (example, phenytoin, rifampin), UDP glucuronosyltransferase family 1 member A9 (UGT1A9) inducers (example, rifampin), or substrates for CYP3A4 with a narrow therapeutic range (example, alfentanil, cyclosporin), or sensitive breast cancer resistance protein (BCRP) substrates (example, pravastatin and folic acid) from 14 days before first dose of study drug until 28 days after last dose of study drug. Systemic use of strong CYP3A4 inhibitors (example, clarithromycin, itraconazole) or UGT1A9 inhibitors (example, probenecid, mefenamic acid) from 7 days before first dose of study drug until 28 days after last dose of study drug History of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence) Had major surgery, (example, requiring general anesthesia) within 4 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study Known or suspected congenital or acquired immunodeficiency; or receipt of immunomodulation therapy such as anti-cancer chemotherapy or radiation therapy; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JNJ-64281802<br>Participants will receive 2 initial loading doses of JNJ-64281802 up to Day 2, followed by a maintenance dose on Days 3, 4, and 5. | Drug: JNJ-64281802<br>* JNJ-64281802 will be administered orally.<br>|
| Placebo Comparator: Placebo<br>Participants will receive oral dose of matching placebo every 8 hour (q8h) and once daily on Day 4 and Day 5. | Drug: Placebo<br>* Matching placebo (PEG400) will be administered orally.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Log10-transformed Dengue Virus (DENV) Ribonucleic Acid (RNA) Viral Load (VL) Curve from Baseline Until Day 5 (AUCD1-D5 [log10VL]) | Area under the log10-transformed DENV RNA VL curve from baseline until Day 5 will be reported. | Baseline, up to Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. | Up to Day 28 | 
| Number of Participants with Clinically Significant Abnormalities in Electrocardiogram (ECGs) | Number of participants with clinically significant abnormalities in ECGs will be reported. | Up to Day 28 | 
| Number of Participants with Clinically Significant Abnormalities in Physical Examination | Number of participants with clinically significant abnormalities in physical examination (head/neck/thyroid, eyes/ears/nose/throat, respiratory, cardiovascular, lymph nodes, abdomen, skin, musculoskeletal, and neurological) will be reported. | Up to Day 28 | 
| Number of Participants with Clinically Significant Abnormalities in Vital Signs | Number of participants with clinically significant abnormalities in vital signs (temperature, pulse/heart rate, respiratory rate, peripheral capillary oxygen saturation [spO2], input-output [I/O] ratio and blood pressure) will be reported. | Up to Day 28 | 
| Number of Participants with Clinically Significant Abnormalities in Laboratory Parameters | Number of participants with clinically significant abnormalities in laboratory parameters (serum chemistry, hematology, and coagulation) will be reported. | Up to Day 28 | 
| Occurrence of Detectable DENV RNA in Primary DENV Infection | Occurrence of detectable DENV RNA in primary DENV infection will be reported. | Up to Day 28 | 
| Time to Undetectable DENV RNA in Primary DENV Infection | Time to undetectable DENV RNA in primary DENV infection will be reported. | Up to Day 28 | 
| Area Under the Concentration Curve During one Dosing Interval (AUCtau) of JNJ-64281802 | AUCtau is defined as area under the concentration curve during one dosing interval of JNJ-64281802. | Predose (day 1, 2, 3, 4 and 5), post dose up to Day 28 | 
| Maximum Observed Analyte Concentration (Cmax) of JNJ-64281802 | Cmax is defined as the maximum observed analyte concentration of JNJ-64281802. | Predose up to 5 days; post dose up to Day 28 | 
| Trough Observed Analyte Concentration (Ctrough) of JNJ-64281802 | Ctrough is defined as observed analyte concentration just prior to the beginning or at the end of a dosing interval of JNJ-64281802. | Predose up to 5 days; post dose up to Day 28 |