A Study of JNJ-64281802 Against Dengue Serotype 1 Infection in a Dengue Human Challenge Model in Healthy Adult Participants

A Phase 2a, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Antiviral Activity, Safety, and Pharmacokinetics of Repeated Oral Doses of JNJ-64281802 Against Dengue Serotype 1 Infection in a Dengue Human Challenge Model in Healthy Adult Participants

The purpose of this study is to assess the antiviral activity of JNJ-64281802 versus placebo in terms of reduction of dengue virus 1 (DENV-1) ribonucleic acid (RNA) viral load (VL).

Study Overview

• Status: Suspended
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: JNJ-64281802 High dose; Drug: JNJ-64281802 Medium dose; Drug: JNJ-64281802 Low dose; Drug: JNJ-64281802 Dosing Regimen X; Drug: JNJ-64281802 Dosing Regimen Y; Drug: JNJ-64281802 Dosing Regimen Z

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, E1 1JT
    • hVIVO Services Limited
• United States
  • New York
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy on the basis of physical examination, medical history, and vital signs performed at screening. If there are abnormalities, the participant may be included only if the investigator judges the abnormalities to be not clinically relevant. This determination must be recorded in the participant's source documents and initialed and dated by the investigator
• Must pass the comprehension test (i.e., obtain a passing score of greater than or equal to (>=) 75 percent (%), with up to 3 attempts in total) indicating that he or she understands the purpose, procedures, and potential risks and benefits of the study, after reading the informed consent and after the investigator or designee has provided detailed information on the study and answered the potential participant's questions
• Must have a blood pressure (after the participant is supine for >=5 minutes) between 90 and 140 millimeters of Mercury (mmHg) systolic, extremes included, and less than or equal to (<=) 90 mmHg diastolic at screening. Two repeat measurements are allowed in the absence of any other concerning health screening issues
• Must have a Body mass index (BMI) (weight in kilogram divided by the square of height in meters) between 18.0 and 33.0 kilogram per meter square (kg/m^2), extremes included, and a body weight of >=50.0 kg at screening
• All women of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin) pregnancy test at screening

Exclusion Criteria:

• Known allergies, hypersensitivity, or intolerance to JNJ-64281802 or its excipients, to a previous vaccination, or to specific medications/animals for which antigens may be in the dengue virus (DENV)-1 challenge strain preparations, including shellfish, fetal bovine serum, L-glutamine, neomycin, and streptomycin
• Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
• Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 6 months before first dose of study drug, or is currently enrolled in an investigational study, or is planning to be enrolled in an investigational study within 90 days after last dose of study drug
• Pregnant, breastfeeding, or planning to become pregnant during the study or within 90 days after last dose of study drug
• Plans to father a child during the study or within 90 days after last dose of study drug

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will receive matching placebo of JNJ-64281802 orally.	Drug: Placebo; Matching placebo will be administered orally.
Experimental: JNJ-64281802 High dose; Participants will receive high dose of JNJ-64281802 orally.	Drug: JNJ-64281802 High dose; JNJ-64281802 high dose will be administered orally.
Experimental: JNJ-64281802 Medium dose; Participants will receive medium dose of JNJ-64281802 orally.	Drug: JNJ-64281802 Medium dose; JNJ-64281802 medium dose will be administered orally.
Experimental: JNJ-64281802 Low dose; Participants will receive low dose of JNJ-64281802 orally.	Drug: JNJ-64281802 Low dose; JNJ-64281802 low dose will be administered orally.
Experimental: JNJ-64281802 Dosing Regimen X; Participants will receive dosing regimen X of JNJ-64281802 orally.	Drug: JNJ-64281802 Dosing Regimen X; JNJ-64281802 dosing regimen X will be administered orally.
Experimental: JNJ-64281802 Dosing Regimen Y; Participants will receive dosing regimen Y of JNJ-64281802 orally.	Drug: JNJ-64281802 Dosing Regimen Y; JNJ-64281802 dosing regimen Y will be administered orally.
Experimental: JNJ-64281802 Dosing Regimen Z; Participants will receive dosing regimen Z of JNJ-64281802 orally.	Drug: JNJ-64281802 Dosing Regimen Z; JNJ-64281802 dosing regimen Z will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the DENV-1 RNA VL-concentration time Curve (VL AUC) from Immediately before Inoculation (Baseline on Day 1) until Day 29	Area under the dengue virus (DENV)-1 ribonucleic acid (RNA) Viral Load (VL) concentration-time curves from immediately before inoculation (baseline on Day 1) until Day 29 will be reported.	Baseline to Day 29

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 85
Number of Participants with Clinically Significant Abnormalities in Physical Examination	Number of participants with clinically significant abnormalities in physical examination will be reported.	Up to Day 85
Number of Participants with Clinically Significant Abnormalities in Vital Signs	Number of participants with clinically significant abnormalities in vital signs (body temperature, pulse/heart rate, systolic and diastolic blood pressure) will be reported.	Up to Day 85
Number of Participants with Clinically Significant Abnormalities in Electrocardiogram (ECGs)	Number of participants with clinically significant abnormalities in electrocardiogram (ECGs) will be reported.	Up to Day 21
Number of Participants with Clinically Significant Abnormalities in Laboratory Parameters	Number of participants with clinically significant abnormalities in laboratory parameters (serum chemistry, hematology, blood coagulation, and urine samples) will be reported.	Up to Day 85
Number of Participants with DENV Infection Associated AEs	Number of participants with DENV infection associated AEs will be reported.	Up to Day 85
Area Under the log10-transformed DENV 1 RNA VL Concentration-time Curves from Immediately before Inoculation (Baseline on Day 1) until Day 29	Area under the log10-transformed DENV 1 RNA VL concentration-time curves from immediately before inoculation (baseline on Day 1) until Day 29 will be reported.	Baseline to Day 29
Peak of Detectable DENV-1 RNA	Peak of detectable DENV-1 RNA will be reported.	Up to Day 85
Duration of Detectable DENV-1 RNA	Duration of detectable DENV-1 RNA will be reported.	Up to Day 85
Time to First Onset of Detectable DENV-1 RNA	Time to first onset of detectable DENV-1 RNA will be reported.	Up to Day 85
Number of Participants with Detectable DENV-1 RNA	Number of participants with detectable DENV-1 RNA will be reported.	Up to Day 85
Area Under the Viremia Curves from Immediately before Inoculation (Baseline on Day 1) until Day 29	Area under the viremia curves from immediately before inoculation (baseline on Day 1) until Day 29 will be reported.	Baseline to Day 29
Area Under the log10-transformed Viremia Curves	Area under the log10-transformed viremia curves will be reported.	Up to Day 85
Peak of Detectable Viremia Level	Peak of detectable viremia level will be reported.	Up to Day 85
Duration of Detectable Viremia	Duration of detectable viremia will be reported.	Up to Day 85
Time to First Onset of Detectable Viremia	Time to first onset of detectable viremia will be reported.	Up to Day 85
Number of Participants with Detectable Viremia	Number of participants with detectable viremia will be reported.	Up to Day 85
Maximum Observed Analyte Concentration (Cmax) of JNJ-64281802	Cmax is the maximum observed analyte concentration.	Day -5: Predose, 1, 2, 4, 6, 8, 10, 12 hours Postdose; Day 21: Predose, 1, 2, 4, 6, 8, 12, 24 and 96 hours Postdose
Minimum Observed Analyte Concentration (Cmin) of JNJ-64281802	Cmin is the minimum observed analyte concentration.	Day 21: Predose, 1, 2, 4, 6, 8, 12, 24 and 96 hours Postdose
Trough Plasma 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.	Day -4, 1, 6, 8, 10, and 15: Predose; Day 21: Predose, 1, 2, 4, 6, 8, 12, 24 and 96 hours Postdose
Average Analyte Concentration (Cavg) of JNJ-64281802	Cavg is defined as average analyte concentration over the dosing interval (tau) and will be calculated as AUCtau/Tau.	Day -5: Predose, 1, 2, 4, 6, 8, 10, 12 hours postdose; Day 21: Predose, 1, 2, 4, 6, 8, 12, 24 and 96 hours Postdose
Time to Reach Maximum Observed Plasma Analyte Concentration (Tmax) of JNJ-64281802	Tmax is defined as the actual sampling time to reach the maximum observed plasma analyte concentration.	Day -5: Predose, 1, 2, 4, 6, 8, 10, 12 hours postdose; Day 21: Predose, 1, 2, 4, 6, 8, 12, 24 and 96 hours Postdose
Fluctuation Index (FI) of JNJ-64281802	FI is the percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100*([Cmax-Cmin]/Cavg).	Day 21: Predose, 1, 2, 4, 6, 8, 12, 24 and 96 hours Postdose
Area Under the Curve from Time Zero to End of Dosing Interval (AUCtau)	The AUCtau is the measure of the plasma analyte concentration from time zero to end of dosing interval. AUC during a dosing interval (τ), calculated by linear-linear trapezoidal summation.	Day -5: Predose, 1, 2, 4, 6, 8, 10, 12 hours postdose; Day 21: Predose, 1, 2, 4, 6, 8, 12, 24 and 96 hours Postdose
Number of Participants with Anti DENV-1 Total IgM and IgG Antibody Titers	Anti-DENV-1 immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies will be measured using enzyme-linked immunosorbent assay (ELISA).	Up to Day 85
Time to First Onset of Anti-DENV-1 Total IgM and IgG Antibody Titers	Time to first onset of anti-DENV-1 total IgM and IgG antibody titers will be reported.	Up to Day 85

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): July 28, 2020
• Primary Completion (Estimated): January 31, 2024
• Study Completion (Estimated): December 9, 2027

Study Registration Dates

• First Submitted: July 17, 2020
• First Submitted That Met QC Criteria: July 17, 2020
• First Posted (Actual): July 21, 2020

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 8, 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: CR108700; 64281802DNG2001 (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 & 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