An Evaluation of Repeated Oral Doses of JNJ-64281802 Against DENV-3 Challenge

• Status: Not yet recruiting
• Trial end date: 2023-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The investigational study drug, JNJ-64281802, is being developed for the prevention and treatment of dengue infection. This study is hypothesizing that the highest dose of the investigational study drug is superior to receiving a placebo with respect to its antiviral activity in healthy adult participants inoculated with Dengue Serotype 3.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Janssen, LP; National Institutes of Health (NIH)

Criteria

Inclusion Criteria for receipt of Study Drug:

1. Male or female.

2. 18 to 50 years of age, inclusive, at time of screening.

3. Healthy on the basis of physical examination, medical history, and vital signs performed at screening.

4. Healthy on the basis of clinical laboratory tests performed at screening.

5. Must pass the comprehension test indicating that the participant 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.

6. Must have a body mass index between 18.0 and 30.0 kg/m2, inclusive, and a body weight of greater than or equal to 50.0 kg at screening.

7. Must have a normal electrocardiogram (ECG, test which displays a person's heartbeat) at screening.

8. Must have a blood pressure (after lying face up for greater than or equal to 5 minutes) between 90 and 140 mmHg systolic and less than or equal to 90 mmHg diastolic at screening.

9. Must complete the informed consent process independently and without assistance and sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.

10. All persons of childbearing potential must have a negative pregnancy test at screening.

11. A woman must be:

1. Not of childbearing potential, or

2. Of childbearing potential and practicing a highly effective, preferably user independent method of contraception and agrees to remain on a highly effective method while receiving study drug and until greater than or equal to 90 days after last dose of study drug.

12. A woman must agree not to donate eggs for the purposes of assisted reproduction during the study and for greater than or equal to 90 days after last dose of study drug.

13. During the study and for greater than or equal to 90 days after last dose of study drug, a male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person. Male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as condoms may break or leak.

14. A male participant must agree not to donate sperm for the purpose of reproduction during the study and for greater than or equal to 90 days after last dose of study drug.

15. Must be willing and able to adhere to the study requirements and lifestyle restrictions:

• Do not take any restricted medications/treatments

• Agree to follow all study requirements

• No unusual strenuous exercise

• Must not donate blood or blood products within 6 months after last dose of study drug

• Must not participate in another investigational study during the study or within 90 days after last dose of study drug

• Must not travel to any dengue-endemic region (as defined by the United States Centers for Disease Control and Prevention

• Must limit the use of food or drinks/beverages containing alcohol to the absolute minimum from 1 day before first dose of study drug until Day 85.

• Must refrain from consumption of grapefruit or grapefruit juice, energy drinks, excessive use of caffeine from 7 days before first dose of study drug until Day 85

• May not use drugs of abuse (including amphetamine, barbiturate, benzodiazepine, cannabinoids, cocaine, methadone, opiates, phencyclidine, and tricyclic antidepressants) until greater than or equal to 3 weeks after last dose of study drug.

• Should not consume any food containing poppy seeds or codeine-containing formulation starting 72 hours before the screening visits and before any visit during the follow-up phase (to avoid a false-positive urine drug test).

• Should follow the restrictions on food and water intake and the instructions for the timing of the standardized meals

16. Available for the duration of the study, which is approximately 85 days after injection of the dengue virus.

Exclusion Criteria for receipt of Study Drug:

1. History of liver or renal impairment; significant cardiac, vascular, pulmonary, gastrointestinal (such as significant diarrhea, constipation lasting greater than 2 days), endocrine, neurologic, hematologic, rheumatologic, neoplastic, autoimmune, or metabolic disturbances.

2. Known allergies, hypersensitivity, or intolerance to the study drug (JNJ-64281802) or its inactive substances, or an acute, life threatening allergic reaction or swelling following study drug administration.

3. History of a severe allergic reaction or anaphylaxis (which is a severe, potentially life-threatening allergic reaction).

4. Taken any substances or therapies that are not allowed before the first dose of study drug.

5. Received an investigational intervention or participated in another investigational clinical trial (including investigational vaccines) 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.

• Important note, COVID-19 vaccines licensed or under Emergency Use Authorization can be received at any time.

6. Females of childbearing potential only: Pregnant as determined by a positive pregnancy blood test, breastfeeding, or planning to become pregnant during the study or within 90 days after last dose of study drug.

7. Plans to father a child during the study or within 90 days after last dose of study drug.

8. Any condition for which, in the opinion of the study doctor, participation would not be in the best interest of the participant.

9. Blood test confirming current infection with human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2), hepatitis B virus (HBV), or hepatitis C virus (HCV), or blood test confirming past or current infection with or vaccination for any of the following flaviviruses: DENV, Yellow Fever virus (YFV), Zika virus (ZIKV), West Nile virus (WNV), St. Louis encephalitis virus (SLEV), or participant testimony confirming past or current infection with Japanese encephalitis virus (JEV).

Note: Blood laboratory testing will assess the presence of antibodies at screening.

10. Recent (in the past 4 weeks) travel to any dengue-endemic region (as defined by the US CDC) or having definite plans to travel to a dengue endemic region. Potential participants may be eligible for enrollment greater than or equal to 4 weeks after their return from a dengue-endemic region.

11. Received or plans to receive:

1. Licensed live attenuated vaccines - within 28 days before first dose of study drug until 28 days after last dose of study drug.

2. Other licensed (not live) vaccines - within 14 days before first dose of study drug until 14 days after last dose of study drug.

3. COVID-19 vaccines, either licensed or under EUA, are allowed at any time during the study however every effort will be made to avoid the above windows of time of administration.

Note: Flavivirus vaccinations are not allowed until 90 days after last dose of study drug.

12. Employee of the study doctor or study site with direct involvement in the proposed study or other studies under the direction of that study doctor or study site, as well as family members of the employees or the investigator.

13. Any clinically relevant skin disease in the past 5 years, such as dermatitis, eczema, drug rash, psoriasis, food allergy resulting in rash, and urticaria.

14. Having donated or lost greater than 1 unit of blood (500 mL) within 60 days or greater than 1 unit of plasma (250 mL) within 7 days before first dose of study drug or having the intention to donate blood or blood products during the study and within 6 months after last dose of study drug.

15. Receipt of blood products within the past 6 months of initiation of study drug or anticipated receipt of any blood products during the 28 days following dengue virus injection.

16. Known or suspected congenital or acquired immunodeficiency or use of immunosuppressive corticosteroids (excluding topical and nasal) or immunosuppressive drugs within 28 days before first dose of study drug until 28 days following the last dose of study drug.

a. An immunosuppressive dose of corticosteroids is defined as greater than or equal to10 mg prednisone equivalent per day for grater than or equal to 14 days.

17. Use of any cytochrome P450 (CYP) 3A4 inhibitors (eg, clarithromycin, itraconazole), CYP3A4 inducers (eg, phenytoin, rifampin), or substrates for CYP3A4 (eg, midazolam, triazolam), CYP2C8 (eg, repaglinide), CYP2C9 (eg, warfarin, tolbutamide), BCRP (eg Pravastatin and folic acid), or CYP2C19 (eg, S-mephenytoin, omeprazole) within 14 days before first dose of study drug.

18. Any significant alcohol or drug abuse in the past 12 months that has caused medical, occupational, or family problems, as indicated by participant history, or positive test result(s) for alcohol or drugs of abuse at screening.

19. Behavioral, cognitive, or psychiatric disease that affects the subject's ability to understand and cooperate with the requirements of the study protocol.

20. Severe asthma (emergency room visit or hospitalization within the last 6 months).

21. Asplenia (the absence of a spleen).

22. Refusal to allow specimen storage for future research.

23. History of risk factors for life-threatening heart rhythm disturbance which includes heart failure, low potassium levels in the blood, family history of fast, chaotic heartbeats known as Long QT Syndrome.

Exclusion Criteria for dengue virus injection:

1. Body temperature greater than or equal to 38.0°C (100.4°F), confirmed by repeat measurements at least 10 minutes after the first measurement.

2. Acute illness.

3. Any other clinical or laboratory finding that would exclude the participant from inoculation (including, but limited to, a positive urine/serum pregnancy test), as assessed by the study doctor.