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

• ClinicalTrials.gov Identifier: NCT04480736
• Recruitment Status: Suspended
• First Posted: July 21, 2020
• Last Update Posted: January 9, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Healthy	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	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• 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
• Actual Study Start Date: July 28, 2020
• Estimated Primary Completion Date: January 31, 2024
• Estimated Study Completion Date: December 9, 2027

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Area Under the DENV-1 RNA VL-concentration time Curve (VL AUC) from Immediately before Inoculation (Baseline on Day 1) until Day 29 [ Time Frame: Baseline to 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.

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, New York

SUNY Upstate Medical University

Syracuse, New York, United States, 13210

United Kingdom

hVIVO Services Limited

London, United Kingdom, E1 1JT

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

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

More Information

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT04480736
• Other Study ID Numbers: CR108700; 64281802DNG2001 ( Other Identifier: Janssen Research & Development, LLC )
• First Posted: July 21, 2020
• Last Update Posted: January 9, 2024
• Last Verified: January 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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
• URL: https://www.janssen.com/clinical-trials/transparency

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Dengue; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral