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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04480736
• Other study ID #: CR108700
• Secondary ID: 64281802DNG2001
• Status: Suspended
• Phase: Phase 2
• Start date: July 28, 2020
• Est. completion date: December 9, 2027

Study information

• Verified date: January 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 54
• Est. completion date: December 9, 2027
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Dengue
• Healthy

Intervention

Drug:
• Placebo
Matching placebo will be administered orally.
• JNJ-64281802 High dose
JNJ-64281802 high dose will be administered orally.
• JNJ-64281802 Medium dose
JNJ-64281802 medium dose will be administered orally.
• JNJ-64281802 Low dose
JNJ-64281802 low dose will be administered orally.
• JNJ-64281802 Dosing Regimen X
JNJ-64281802 dosing regimen X will be administered orally.
• JNJ-64281802 Dosing Regimen Y
JNJ-64281802 dosing regimen Y will be administered orally.
• JNJ-64281802 Dosing Regimen Z
JNJ-64281802 dosing regimen Z will be administered orally.

Locations

Country	Name	City	State
United Kingdom	hVIVO Services Limited	London
United States	SUNY Upstate Medical University	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of Participants with DENV Infection Associated AEs	Number of participants with DENV infection associated AEs will be reported.	Up to Day 85
Secondary	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
Secondary	Peak of Detectable DENV-1 RNA	Peak of detectable DENV-1 RNA will be reported.	Up to Day 85
Secondary	Duration of Detectable DENV-1 RNA	Duration of detectable DENV-1 RNA will be reported.	Up to Day 85
Secondary	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
Secondary	Number of Participants with Detectable DENV-1 RNA	Number of participants with detectable DENV-1 RNA will be reported.	Up to Day 85
Secondary	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
Secondary	Area Under the log10-transformed Viremia Curves	Area under the log10-transformed viremia curves will be reported.	Up to Day 85
Secondary	Peak of Detectable Viremia Level	Peak of detectable viremia level will be reported.	Up to Day 85
Secondary	Duration of Detectable Viremia	Duration of detectable viremia will be reported.	Up to Day 85
Secondary	Time to First Onset of Detectable Viremia	Time to first onset of detectable viremia will be reported.	Up to Day 85
Secondary	Number of Participants with Detectable Viremia	Number of participants with detectable viremia will be reported.	Up to Day 85
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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 (t), 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
Secondary	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
Secondary	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