Dengue 3 Human Infection Model (DENV-3)

NCT ID: NCT04298138

Last Updated: 2024-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-03
• Study Completion Date: 2021-12-14

Brief Summary

To evaluate the effectiveness of candidate dengue vaccine formulations, it is prudent to develop an appropriate challenge model. This study will examine the safety and effectiveness of the Dengue 3 Live Virus Human Challenge (DENV-3-LVHC) product and assess the ability of this virus strain to elicit an uncomplicated dengue-like illness.

Detailed Description

Healthy subjects between 18 and 45 years old will be inoculated with Dengue 3 Live Virus Human Challenge (DENV-3-LVHC) in a dose ranging study. Subjects will be closely monitored for the first 28 days with continued follow up through 6 months. Clinical and laboratory parameters, viremia and antibody levels will be assessed. The goal is to determine the dose that produces uncomplicated dengue-like illness.

Conditions

Dengue

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Low dose DENV-3-LVHC

Dengue-3 Virus-Live Virus Human Challenge (DENV-3-LVHC) single low dose (0.5 mL of 1.4 x 10\^3 plaque forming units/milliliter (PFU/mL) inoculated subcutaneously

Group Type: EXPERIMENTAL

Dengue virus 3 Live Virus Human Challenge (DENV-3-LVHC)

Intervention Type: BIOLOGICAL

Dengue subtype 3 Challenge Virus (DENV-3) strain CH53489 administered as a single injection.

Medium dose DENV-3-LVHC

Dengue-3 Virus-Live Virus Human Challenge (DENV-3-LVHC) single medium dose (0.5 mL of 1.4 x 10\^4 plaque forming units/milliliter (PFU/mL) inoculated subcutaneously

Group Type: EXPERIMENTAL

Dengue virus 3 Live Virus Human Challenge (DENV-3-LVHC)

Intervention Type: BIOLOGICAL

Dengue subtype 3 Challenge Virus (DENV-3) strain CH53489 administered as a single injection.

High dose DENV-3-LVHC

Dengue-3 Virus-Live Virus Human Challenge (DENV-3-LVHC) single high dose (0.5 mL of 1.4 x 10\^5 plaque forming units/milliliter (PFU/mL) inoculated subcutaneously

Group Type: EXPERIMENTAL

Dengue virus 3 Live Virus Human Challenge (DENV-3-LVHC)

Intervention Type: BIOLOGICAL

Dengue subtype 3 Challenge Virus (DENV-3) strain CH53489 administered as a single injection.

Interventions

Dengue virus 3 Live Virus Human Challenge (DENV-3-LVHC)

Dengue subtype 3 Challenge Virus (DENV-3) strain CH53489 administered as a single injection.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Age 18-45 at the time of consent

2. Ability and willingness to sign informed consent

3. Passing score on comprehension test of at least 75%, with up to 3 attempts

4. Available for the study period

5. Willing to use contraception for the duration of the study

6. Provide consent for release of medical history records from primary care physician, college or university, urgent care or emergency room visit

Exclusion Criteria

1. Female: pregnant or lactating

2. Heavy menstrual bleeding within the last 6 months- menstrual periods lasting longer than 6 days, or requiring 5 or more pads or tampons per day.

3. Female subjects using an intrauterine device (IUD) or Mirena®

4. Female subjects with fibroids or uterine polyps, endometriosis, adenomyosis, and uterine scarring (e.g., after D&C)

5. Blood tests confirming infection with human immunodeficiency virus- 1 (HIV-1), hepatitis C, hepatitis B (assessed by HbsAg) virus, or positive antibodies to the flaviviruses (FV) dengue, West Nile, Yellow Fever, Japanese encephalitis, or Zika.

6. Active Diabetes or active peptic ulcer disease (PUD)

7. Chronic obstructive pulmonary disease (COPD) or coronary artery disease (CAD)

8. 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)

9. Current, or a history of, auto-immune disease

10. History of Guillain-Barré syndrome (GBS)

11. Any history of FV infection or FV vaccination; or planned FV vaccination, outside the study protocol, during the study period

12. Diagnosis with Bipolar Disorder or Schizophrenia, hospitalization in the past year for a mental health disorder, or any other psychiatric condition, which in the opinion of the investigator prevents the subject from participating in the study.

13. Planned travel during the study period (180 days) which would interfere with the ability to complete all study visits

14. Recent (in the past 4 weeks) travel to any dengue endemic area. These potential subjects may be eligible for enrollment a minimum of 4 weeks later

16. Subjects with the following grade 2 or greater lab abnormalities: Creatinine; Liver Function Tests - ALT, AST; Hemoglobin (females and males); White Blood Cell (WBC) decrease; Platelets decreased; Prothrombin Time (PT); Partial Thromboplastin Time (PTT); Fibrinogen decrease

17. Significant screening physical examination abnormalities at the discretion of the investigator

18. Women who intend to become pregnant or men who intend to father a child during the study period (approximately 180 days)

19. Hives, shortness of breath, swelling of the lips or throat, or hospitalization related to a previous vaccination or an allergy to specific medications/animals for which antigens may be in the virus preparations to include: shellfish allergy, fetal bovine serum, L-glutamine, neomycin and streptomycin

20. Planning to donate blood in the 1 year following inoculation with dengue

21. Recent blood donation within prior 56 days of inoculation

22. Receipt of blood products or antibodies within 56 days of inoculation or during the study period

23. Participation (active or follow-up phase) or planned participation in another vaccine, drug, medical device, or medical procedure clinical trial in the 4 weeks prior to this trial, during the trial, or 6 months following inoculation in this clinical trial

24. Recent or scheduled receipt of any vaccine 4 weeks prior to or after virus inoculation

25. Beliefs that bar the administration of blood products or transfusions

26. Positive urine screen for cocaine, amphetamines, or opiates

27. Currently taking Methadone or Suboxone

28. Currently taking anti-coagulant medication, aspirin or non-steroidal anti-inflammatory drugs (NSAIDs)

29. Chronic migraine headaches, defined as more than 15 headache days per month over a 3-month period of which more than 8 are migraines, in the absence of medication over use

30. Chronic medical condition that, in the opinion of the investigator, impacts subject safety.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Walter Reed Army Institute of Research (WRAIR)

FED

Sponsor Role: collaborator

U.S. Army Medical Research and Development Command

FED

Sponsor Role: collaborator

State University of New York - Upstate Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen J Thomas, MD

Role: PRINCIPAL_INVESTIGATOR

State University of New York, Upstate Medical University (SUNY-UMU)

Locations

State University of New York, Upstate Medical University (SUNY-UMU)

Syracuse, New York, United States

Countries

United States

Other Identifiers

2019-01-UMU

Identifier Type: -

Identifier Source: org_study_id