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

• ClinicalTrials.gov Identifier: NCT04906980
• Recruitment Status: Terminated
• First Posted: May 28, 2021
• Results First Posted: March 1, 2024
• Last Update Posted: March 1, 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 investigate the antiviral activity of JNJ-64281802 versus placebo in terms of reduction of dengue virus (DENV) ribonucleic acid (RNA) in primary DENV infection.

Condition or disease	Intervention/treatment	Phase
Dengue	Drug: JNJ-64281802; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 24, 2022
• Actual Primary Completion Date: September 24, 2022
• Actual Study Completion Date: March 21, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Area Under the Log10-Transformed Dengue Virus (DENV) RiboNucleic Acid (RNA) Viral Load (VL) Curve From Baseline Until Day 5 (AUCD1-D5 [log10VL]). [ Time Frame: Baseline (Day 1) upto Day 5 ]
   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]).

Secondary Outcome Measures :

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: From Day 1 up to the last onsite visit (Day 30) ]
   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.
2. Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings [ Time Frame: From Day 1 up to the last onsite visit (Day 30) ]
   Number of participants with clinically significant abnormalities in ECGs parameters as assessed based on investigator's discretion were reported.
3. Number of Participants With Clinically Significant Abnormalities in Physical Examination [ Time Frame: From Day 1 up to the last onsite visit (Day 30) ]
   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.
4. Number of Participants With Clinically Significant Abnormalities in Vital Signs [ Time Frame: From Day 1 up to the last onsite visit (Day 30) ]
   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.
5. Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters [ Time Frame: From Day 1 up to the last onsite visit (Day 30) ]
   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.
6. Plasma Concentrations of JNJ-64281802 [ Time Frame: 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 ]
   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.
7. Number of Participants With Occurrence of Detectable Dengue Virus (DENV) RiboNucleic Acid (RNA) in Primary DENV Infection [ Time Frame: 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 ]
   Number of participants with occurrence of detectable DENV RNA in primary DENV infection was a planned analysis.
8. Time to Undetectable Dengue Virus (DENV) RiboNucleic Acid (RNA) in Primary DENV Infection [ Time Frame: 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 DENV RNA in primary DENV infection was a planned analysis.
9. Area Under the Plasma Concentration Time Curve During One Dosing Interval (AUC[Tau]) of JNJ-64281802 [ Time Frame: 0, 8, 16 hours pre-dose on Day 1; 4 and 12 hours post-dose on Day 1 ]
   AUC[tau] is defined as area under the plasma concentration time curve during one dosing interval of JNJ-64281802.
10. Trough (Pre-dose) Analyte Concentration (Ctrough) of JNJ-64281802 [ Time Frame: 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 ]
    Ctrough is defined as plasma concentration just prior to the beginning or at the end of a dosing interval of JNJ-64281802.
11. Maximum Observed Plasma Concentration (Cmax) of JNJ-64281802 [ Time Frame: 0, 8, 16 hours pre-dose on Day 1; 4 and 12 hours post-dose on Day 1 ]
    Cmax is defined as the maximum observed plasma concentration of JNJ-64281802.

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

Singapore

Singapore General Hospital

Singapore, Singapore, 169608

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

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

  Study Documents (Full-Text)

Documents provided by Janssen Research & Development, LLC:

Study Protocol  [PDF] June 6, 2022

Statistical Analysis Plan  [PDF] October 4, 2023

More Information

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT04906980
• Other Study ID Numbers: CR108919; 64281802DNG2003 ( Other Identifier: Janssen Research & Development, LLC )
• First Posted: May 28, 2021
• Results First Posted: March 1, 2024
• Last Update Posted: March 1, 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 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
• 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
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

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