JNJ-64281802 for Dengue Fever

Recruiting at 1 trial location

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Strong CYP3A4 inhibitors

Disqualifiers: Liver impairment, HIV, Hepatitis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 85

Duration: 21 days

56 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug, JNJ-64281802, to see if it can prevent or treat dengue fever in healthy adults exposed to Dengue Serotype 3. The drug aims to stop the virus from multiplying.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain medications, especially those affecting liver enzymes like CYP3A4, CYP2C8, and CYP2C9, are restricted. It's best to discuss your current medications with the study doctor to see if they are allowed.

What safety information is available for JNJ-64281802, a JAK inhibitor, in humans?

JNJ-64281802 is a JAK inhibitor, and similar drugs have been used for conditions like rheumatoid arthritis. Common safety concerns include an increased risk of infections, such as tuberculosis and herpes zoster (shingles), and potential risks for blood clots and heart issues. Long-term safety data is still needed, and patients with certain health conditions may require careful monitoring. ^{1 2 3 4 5}

Research Team

Anna Durbin, MD

Principal Investigator

Center for Immunization Research, Johns Hopkins School of Public Health

Eligibility Criteria

Healthy adults aged 18-55 with normal clinical tests, ECGs, and blood pressure can join this trial. They must not be pregnant or planning pregnancy, agree to use contraception, avoid donating blood or sperm for a certain period, and refrain from drug abuse. Exclusion includes HIV/HBV/HCV infection, recent travel to dengue regions, immunodeficiency conditions, significant alcohol/drug abuse history.

Inclusion Criteria

My heart test (ECG) and blood pressure are normal.

Must pass comprehension assessment after reading informed consent and receiving detailed study information

I am healthy according to recent medical exams and tests.

Exclusion Criteria

I am at risk for serious heart rhythm problems.

Known allergies or severe allergic reactions to study drug or its components

Clinically relevant skin diseases, recent blood donation, or receipt of blood products

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 8 weeks

Multiple visits for various screenings

Treatment

Participants receive repeated oral doses of JNJ-64281802 or placebo and are inoculated with rDEN3delta30

21 days

Inpatient visits for intensive PK sampling and outpatient visits for evaluation

Follow-up

Participants are monitored for safety, tolerability, and antiviral activity after treatment

64 days

Final visit on Study Day 85

Treatment Details

Interventions

• JNJ-64281802

Trial Overview The study is testing JNJ-64281802's effectiveness in preventing/treating dengue fever compared to a placebo. Participants will receive different dosing regimens of the drug (weekly Y1/Z2 or daily X) including high and medium/low doses versus placebo after being exposed to Dengue Serotype 3 virus.

Participant Groups

Group I: Cohort 1 - Group 2 JNJ Medium Dose Experimental Treatment 1 Intervention

Group 2 includes Medium and low dose, 14 participants total. Enrolled after completion of Group 1a.

Group II: Cohort 1 - Group 2 JNJ Low Dose Experimental Treatment 1 Intervention

Group 2 includes Medium and low dose, 14 participants total. Enrolled after completion of Group 1a.

Group III: Cohort 1 - Group 1 JNJ High Dose Experimental Treatment 1 Intervention

Sentinel high-dose. Four participants will be enrolled in Group 1a before enrolling the remaining participants to Group 1b (12 participants total in Group 1, all same dosing regimen). Note group 1a and group 1b are combined into one arm, because the dosing regimen is the same and they were not separated during final statistical analysis.

Group IV: Cohort 1 - Group 1/2 Placebo Placebo Group 1 Intervention

Matching placebo. Note Group 1 placebo and group 2 placebo are combined per sponsor data analysis.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Janssen, LP

Industry Sponsor

Trials

169

Recruited

329,000+

Founded

1953

Headquarters

Beerse, Belgium

Known For

Mental Health Therapies

Top Products

Imodium, Remicade, Invega, Procrit

Joaquin Duato

Janssen, LP

Chief Executive Officer since 2022

MBA from ESADE Business School

Biljana Naumovic

Janssen, LP

Chief Medical Officer since 2023

MD from Belgrade University Medical School

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

JAK inhibitors (JAKinibs) are effective treatments for rheumatoid arthritis and other immune-mediated inflammatory diseases, with low incidence rates of serious adverse drug reactions, although monitoring for infections like tuberculosis is crucial.

While JAKinibs generally do not increase the risk of malignancy or serious cardiac events, long-term safety data is still needed, especially for specific populations at risk, such as older patients or those with a history of diverticulitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selectivity of Janus Kinase Inhibitors in Rheumatoid Arthritis and Other Immune-Mediated Inflammatory Diseases: Is Expectation the Root of All Headache? Harigai, M., Honda, S.[2021]

Janus kinase inhibitors (JAKi) are commonly used for treating immune-mediated inflammatory diseases like psoriatic arthritis, but recent studies have raised safety concerns, particularly in patients over 50 with cardiac risk factors.

This review summarizes the latest safety data for various JAKi, including tofacitinib and upadacitinib, and discusses findings from an oral surveillance study to provide context for these safety issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janus Kinase Inhibitors: Safety in Patients With Psoriatic Arthritis. Nash, P.[2022]

The study analyzed the safety profiles of antirheumatic agents, specifically TNF inhibitors, IL-6 inhibitors, and methotrexate, using the Japanese Adverse Drug Event Report database, revealing increased risks for serious adverse events like tuberculosis and malignant tumors associated with these drugs.

Different antirheumatic agents showed varying time-to-onset for serious adverse events, with TNF inhibitors having a median onset of 501 days for tuberculosis, while methotrexate had a longer median onset of 537 days, indicating the need for tailored monitoring strategies in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Serious Adverse Event Profiles Among Antirheumatic Agents Using Japanese Adverse Drug Event Report Database. Matsuoka, Y., Narukawa, M.[2020]

This study aims to assess the safety profile of Janus Kinase inhibitors (JAKis) in rheumatoid arthritis patients by quantifying the risks of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), and serious viral infections using data from the Danish DANBIO registry, involving patients treated from January 2017 to December 2022.

The research will compare JAKi users to those using tumor necrosis factor α inhibitors (TNF-αi) to better understand the incidence of these safety concerns, using advanced statistical methods to ensure accurate risk assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK-inhibitors and risk on serious viral infection, venous thromboembolism and cardiac events in patients with rheumatoid arthritis: A protocol for a prevalent new-user cohort study using the Danish nationwide DANBIO register. Faquetti, ML., Vallejo-Yagüe, E., Cordtz, R., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Selectivity of Janus Kinase Inhibitors in Rheumatoid Arthritis and Other Immune-Mediated Inflammatory Diseases: Is Expectation the Root of All Headache? [2021]

2. Canada pubmed.ncbi.nlm.nih.gov

Janus Kinase Inhibitors: Safety in Patients With Psoriatic Arthritis. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of Serious Adverse Event Profiles Among Antirheumatic Agents Using Japanese Adverse Drug Event Report Database. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

JAK-inhibitors and risk on serious viral infection, venous thromboembolism and cardiac events in patients with rheumatoid arthritis: A protocol for a prevalent new-user cohort study using the Danish nationwide DANBIO register. [2023]