NCT05048875

An Evaluation of Repeated Oral Doses of JNJ-64281802 Against DENV-3 Challenge

Phase 2a, Randomized, Doubleblind, Placebo-controlled Trial Evaluating the Antiviral Activity, Safety and Pharmacokinetics of Repeated Oral Doses of JNJ-64281802 Against Dengue-3 Infection in a Dengue Human Challenge Model in Healthy Adults

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 56 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

The investigational study drug, JNJ-64281802, is being developed for the prevention and treatment of dengue infection. This study is hypothesizing that the highest dose of the investigational study drug is superior to receiving a placebo with respect to its antiviral activity in healthy adult participants inoculated with Dengue Serotype 3.

Detailed description

This study is a multicenter, randomized, placebo-controlled, double-blind, interventional Phase 2a, study in normal healthy adult subjects 18 - 55 years of age, inclusive, recruited from the metropolitan Baltimore/Washington, DC area \& Burlington/Vermont. The study follows an adaptive 2-stage design consisting of 2 cohorts, each with up to 3 groups. The 2 cohorts will be enrolled in a staggered manner. As a safety measure, a sentinel group of 4 participants will be enrolled in Cohort 1 (Group 1a) before enrolling the remaining participants (Group 1b and Group 2) in the cohort. The purpose of this study is to evaluate the clinical and virologic response to repeated doses of investigation product JNJ-64281802 when administered orally in healthy, DENV and ZIKV-naïve, non-pregnant, adult volunteers who are subsequently inoculated with rDEN3delta30, a recombinant DENV-3 strain, to explore the antiviral activity of repeated oral doses of JNJ-64281802 versus placebo. The safety, tolerability, PK, and the relationship between the PK and antiviral activity of JNJ-64281802 will also be evaluated. Placebo recipients are included in the study as a control to better assess study agent associated versus non-study agent associated AEs and to act as infectivity controls following administration of rDEN3delta30. After providing written informed consent, subjects will undergo eligibility screening, including medical history, physical examination, hematology testing, liver and renal function testing, human immunodeficiency virus (HIV) screening, hepatitis B and C screening, urinalysis, urine toxicology screening, ECG screening, alcohol breath test screening (per PI/provider discretion), COVID-19 testing (if determined necessary by the clinician or per guidelines), and serology screening for previous infection of DENV and ZIKV (Cohort 1) and DENV, ZIKV, West Nile virus, and SLEV (Cohort 2). Serum or urine pregnancy testing will be performed on applicable persons of childbearing potential. All screening tests must be performed within 60 days of initiation of JNJ-64281802 study agent at Study Day -5 (Cohort 1) or Study Day -2 (Cohort 2). HIV screening must be performed within 2 weeks of JNJ-64281802 study agent administration. Pregnancy screening will occur at applicable screening visit(s), be repeated on the first day of JNJ-64281802 administration prior to administration, and on the day of inoculation with rDEN3delta30 prior to inoculation with rDEN3delta30. All clinically significant abnormalities will be reviewed with subjects and referral for follow-up care will be provided. Subjects will be determined to be eligible based on the inclusion and exclusion criteria for this protocol. For subjects who are eligible, the Study Day -5 (Cohort 1) or Study Day -2 (Cohort 2) visit will be scheduled for initiation of JNJ-64281802. For Cohort 1: Subjects will present to the inpatient unit on Study Day -6. After eligibility criteria have been reviewed and confirmed, subjects will be admitted during this period of intensive PK sampling. Dosing with JNJ-64281802 or placebo will begin on Study Day -5. Discharge will occur on Study Day -4. Dosing with JNJ-64281802 will be observed in-clinic on Days -5, -4, -1, 1, 3, 5, 7, 9, 11, 14, 16, 18, and 21. Subjects will have phone contact on Days -3, -2, 2, 4, 6, 8, 10, 12, 13, 15, 17, 19, and 20 to record time of dose, time of last food intake, and review AEs and concomitant therapy. Daily dosing with JNJ-64281802 or placebo will occur from Study Day -5 through Study Day 21. On Study Day 21 subjects will present to the unit for a second intensive PK sampling period for a full day. On Study Day 1, all subjects will be challenged with rDEN3delta30. For Cohort 2: Subjects will present to the inpatient unit on Study Day -3. After eligibility criteria have been reviewed and confirmed, subjects will be admitted during this period of intensive PK sampling. Dosing with JNJ-64281802 or placebo will begin on Study Day -2. Discharge will occur on Study Day 1. Dosing with JNJ-64281802 will be observed in-clinic on Days -2, -1, 1, 4, 6, 8, 11, 13, 15, 18, and 21 for the daily dosing regimen and on Days -2, -1, 1, 8 and 15 for the weekly dosing regimens. In the daily dosing regimen with JNJ-64281802 or placebo, twice daily dosing will occur from Study Day -2 to Study Day -1, and daily dosing from Study Day 1 to Study Day 21. In the weekly dosing regimens, twice daily dosing will occur from Study Day -2 to Study Day -1, and weekly dosing which will occur on Study Day 1, Study Day 8, and Study Day 15. On Study Day 21 for the daily regimen, and on Study Day 15 for the weekly regimens, subjects will present to the unit for a second intensive PK sampling period for a full day. On Study Day 1, all subjects will be challenged with rDEN3delta30. During the inpatient visits on Study Day -6 to -4 (Cohort 1) and Study Day -3 to 1 (Cohort 2), the subjects will be evaluated by a clinician and will have blood drawn for clinical laboratory studies, virologic assays, and immunologic assays. During the outpatient visits subjects will return to the clinic for evaluation and for blood draw as specified in the Schedule of Procedures. Study Day 85 will be the final visit for Cohort 1. Study Day 85 will be the final visit for Cohort 2\*. Subjects will have their temperature measured in clinic or measure their temperatures at home twice daily from Study Day 1 through Study Day 29.

Conditions

• Dengue

Interventions

Type	Name	Description
DRUG	Cohort 1 - Group 1 JNJ High Dose	High dose: 600-mg loading dose for 5 days/200-mg maintenance dose for 21 days
DRUG	Cohort 1 - Group 2 JNJ Medium Dose	Medium dose: 200-mg loading dose for 5 days/50-mg maintenance dose for 21 days
DRUG	Cohort 1 - Group 2 JNJ Low Dose	Low dose: 40-mg loading dose for 5 days/10-mg maintenance dose for 21 days
DRUG	Cohort 1 - Group 1/2 Placebo	Matching placebo. Note Group 1 placebo and group 2 placebo are combined per sponsor data analysis.

Timeline

• Start date: 2022-02-03
• Primary completion: 2023-05-16
• Completion: 2024-09-10
• First posted: 2021-09-17
• Last updated: 2025-04-24
• Results posted: 2025-04-24

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study