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

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

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.

Study Overview

• Status: Terminated
• Conditions: Dengue
• Intervention / Treatment: Drug: JNJ-64281802; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 169608
    • Singapore General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JNJ-64281802; 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; JNJ-64281802 will be administered orally.
Placebo Comparator: Placebo; Participants will receive oral dose of matching placebo every 8 hour (q8h) and once daily on Day 4 and Day 5.	Drug: Placebo; Matching placebo (PEG400) will be administered orally.

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]).	The antiviral activity of JNJ-64281802 versus placebo in terms of reduction of DENV RNA in participants with a primary DENV infection was planned to be measured by the area under the log10-transformed DENV RNA viral load concentration-time curves from baseline (Day 1) until Day 5 (AUCD1-D5 [log10VL]).	Baseline (Day 1) upto Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (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. TEAEs were those AE events that occurred at or after the initial administration of study intervention through the last onsite visit.	From Day 1 up to the last onsite visit (Day 30)
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings	Number of participants with clinically significant abnormalities in ECGs parameters as assessed based on investigator's discretion were reported.	From Day 1 up to the last onsite visit (Day 30)
Number of Participants With Clinically Significant Abnormalities in Physical Examination	Number of participants with clinically significant abnormalities in physical examination parameters (head/neck/thyroid, eyes/ears/nose/throat, respiratory, cardiovascular, lymph nodes, abdomen, skin, musculoskeletal, and neurological) as assessed based on investigator's discretion were reported.	From Day 1 up to the last onsite visit (Day 30)
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) as assessed based on investigator's discretion were reported.	From Day 1 up to the last onsite visit (Day 30)
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) were reported. Clinical significance was defined as per investigator's judgement.	From Day 1 up to the last onsite visit (Day 30)
Plasma Concentrations of JNJ-64281802	Plasma Concentrations of JNJ-64281802 was assessed. Due to small number of enrolled participants, no summary statistics analysis was performed. Participant wise data were reported for this outcome measure.	Predose: 0, 8, 16 hours on Day 1; 24, 32, 40 hours on Day 2; Day 4, Day 5; and Post dose: 4, 12 hours on Day 1; 28, 36 hours on Day 2; 48 hours on Day 3; Day 6, Day 14, Day 21, Day 28
Number of Participants With Occurrence of Detectable Dengue Virus (DENV) RiboNucleic Acid (RNA) in Primary DENV Infection	Number of participants with occurrence of detectable DENV RNA in primary DENV infection was a planned analysis.	Predose: 24 hour on Day 2; Post dose: 12 hour on Day 1; 36 hour on Day 2; Days 3, 4, 5, 6, 7, 8, 9, 14, 21 and 28
Time to Undetectable Dengue Virus (DENV) RiboNucleic Acid (RNA) in Primary DENV Infection	Time to undetectable DENV RNA in primary DENV infection was a planned analysis.	Predose: 24 hour on Day 2; Post dose: 12 hour on Day 1; 36 hour on Day 2; Days 3, 4, 5, 6, 7, 8, 9, 14, 21 and 28
Area Under the Plasma Concentration Time Curve During One Dosing Interval (AUC[Tau]) of JNJ-64281802	AUC[tau] is defined as area under the plasma concentration time curve during one dosing interval of JNJ-64281802.	0, 8, 16 hours pre-dose on Day 1; 4 and 12 hours post-dose on Day 1
Trough (Pre-dose) Analyte Concentration (Ctrough) of JNJ-64281802	Ctrough is defined as plasma concentration just prior to the beginning or at the end of a dosing interval of JNJ-64281802.	Pre-dose on Day 1: 0 hour, 8 hour, 16 hour; pre-dose on Day 2: 24 hour, 32 hour, 40 hour; pre-dose on Day 4 and Day 5
Maximum Observed Plasma Concentration (Cmax) of JNJ-64281802	Cmax is defined as the maximum observed plasma concentration of JNJ-64281802.	0, 8, 16 hours pre-dose on Day 1; 4 and 12 hours post-dose on Day 1

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2022
• Primary Completion (Actual): September 24, 2022
• Study Completion (Actual): March 21, 2023

Study Registration Dates

• First Submitted: May 26, 2021
• First Submitted That Met QC Criteria: May 26, 2021
• First Posted (Actual): May 28, 2021

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Dengue
• Other Study ID Numbers: CR108919; 64281802DNG2003 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson and Johnson is available at www.janssen.com/clinical- trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes