Assessment of a Dengue-1-Virus-Live Virus Human Challenge - (DENV-1-LVHC) Virus Strain

NCT ID: NCT02372175

Last Updated: 2019-07-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2019-06-28

Brief Summary

To evaluate the effectiveness of candidate dengue vaccine formulations, it is prudent to develop an appropriate challenge model. To this end, this first-in-human study will examine the safety and effectiveness of the Dengue 1 Live Virus Human Challenge (DENV-1-LVHC) product and assess the ability of this virus strain to elicit an uncomplicated dengue-like illness.

Conditions

Dengue

Study Design

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

Study Groups

Low dose DENV-1-LVHC

Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC) single low dose (0.5 mL of 6.5 x 10\^3 plaque forming units/milliliter (PFU/mL) inoculated subcutaneously

Group Type: EXPERIMENTAL

Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC)

Intervention Type: BIOLOGICAL

Dengue subtype 1 Challenge Virus (DENV-1) strain 45AZ5 administered as a single injection.

Medium dose DENV-1-LVHC

Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC) single medium dose (0.5 mL of 6.5 x 10\^4 PFU/mL) inoculated subcutaneously

Group Type: EXPERIMENTAL

Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC)

Intervention Type: BIOLOGICAL

Dengue subtype 1 Challenge Virus (DENV-1) strain 45AZ5 administered as a single injection.

High dose DENV-1-LVHC

Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC) single high dose (0.5 mL of 6.5 x 10\^5 PFU/mL) inoculated subcutaneously

Group Type: EXPERIMENTAL

Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC)

Intervention Type: BIOLOGICAL

Dengue subtype 1 Challenge Virus (DENV-1) strain 45AZ5 administered as a single injection.

Interventions

Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC)

Dengue subtype 1 Challenge Virus (DENV-1) strain 45AZ5 administered as a single injection.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Healthy, male or non-pregnant, non-lactating female

2. Age 18-45

3. Ability and willingness to sign informed consent

4. Passing score on comprehension test would be 75%, with up to 3 attempts

5. Available for the study period

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

7. 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, dysmenorrhea, 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 surface antigen, or flavi viruses (FV) to include dengue fever, West Nile, Yellow Fever, and Japanese encephalitis.

6. Diabetes, chronic obstructive pulmonary disease (COPD), peptic ulcer disease (PUD), or coronary artery disease (CAD)

7. Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)

8. Immediate family member (e.g. parent, sibling, child) with current, or a history of immunodeficiency or autoimmune disease

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. History of Bipolar Disorder, 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

15. Any laboratory abnormalities in the tests specified in Table 19 and Table 20 of the protocol. Note: these laboratory tests can be repeated if the screening physician believes 1) it is thought to be a normal variant of a healthy state or 2) it is a suspected laboratory error

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

17. Women who intend to become pregnant or men who intend to father a child during the study period (approximately 6 months)

18. 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

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

20. Participation 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

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

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

23. Currently taking Methadone or Suboxone

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

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

26. 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

State University of New York - Upstate Medical University

OTHER

Sponsor Role: collaborator

U.S. Army Medical Research and Development Command

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Timothy P Endy, MD, MPH

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

References

Endy TP, Wang D, Polhemus ME, Jarman RG, Jasper LE, Gromowski G, Lin L, De La Barra RA, Friberg H, Currier JR, Abbott M, Ware L, Klick M, Paolino KM, Blair DC, Eckels K, Rutvisuttinunt W, Thomas SJ. A Phase 1, Open-Label Assessment of a Dengue Virus-1 Live Virus Human Challenge Strain. J Infect Dis. 2021 Feb 3;223(2):258-267. doi: 10.1093/infdis/jiaa351.

Reference Type: DERIVED

PMID: 32572470 (View on PubMed)

Other Identifiers

S-14-09

Identifier Type: -

Identifier Source: org_study_id