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

Dengue Clinical Trial

Official title:

Phase One, Open Label, Assessment of a Dengue-1-Virus-Live Virus Human Challenge - (DENV-1-LVHC) Virus Strain

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02372175
• Other study ID #: S-14-09
• Status: Completed
• Phase: Phase 1
• Start date: October 2015
• Est. completion date: June 28, 2019

Study information

• Verified date: July 2019
• Source: U.S. Army Medical Research and Development Command
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: June 28, 2019
• Est. primary completion date: June 28, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dengue

Intervention

Biological:
• Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC)
Dengue subtype 1 Challenge Virus (DENV-1) strain 45AZ5 administered as a single injection.

Locations

Country	Name	City	State
United States	State University of New York, Upstate Medical University (SUNY-UMU)	Syracuse	New York

Sponsors (2)

Lead Sponsor	Collaborator
U.S. Army Medical Research and Development Command	State University of New York - Upstate Medical University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Abnormal Laboratory Measurements		28 days post virus inoculation or 7 days post hospitalization, whichever is later
Primary	Intensity of Abnormal Laboratory Measurements		28 days post virus inoculation or 7 days post hospitalization, whichever is later
Primary	Duration of Abnormal Laboratory Measurements		28 days post virus inoculation or 7 days post hospitalization, whichever is later
Primary	Occurrence of Solicited Injection Site Symptoms		28 days post virus inoculation or 7 days post hospitalization, whichever is later
Primary	Intensity of Solicited Injection Site Symptoms		28 days post virus inoculation or 7 days post hospitalization, whichever is later
Primary	Duration of Solicited Injection Site Symptoms		28 days post virus inoculation or 7 days post hospitalization, whichever is later
Primary	Occurrence of unsolicited Injection Site Symptoms		28 days post virus inoculation or 7 days post hospitalization, whichever is later
Primary	Intensity of Unsolicited Injection Site Symptoms		28 days post virus inoculation or 7 days post hospitalization, whichever is later
Primary	Duration of Unsolicited Injection Site Symptoms		28 days post virus inoculation or 7 days post hospitalization, whichever is later
Primary	Occurrence of Solicited Systemic Symptoms		28 days post virus inoculation or 7 days post hospitalization, whichever is later
Primary	Intensity of Solicited Systemic Symptoms		28 days post virus inoculation or 7 days post hospitalization, whichever is later
Primary	Duration of Solicited Systemic Symptoms		28 days post virus inoculation or 7 days post hospitalization, whichever is later
Primary	Occurrence of Unsolicited Systemic Symptoms		28 days post virus inoculation or 7 days post hospitalization, whichever is later
Primary	Intensity of Unsolicited Systemic Symptoms		28 days post virus inoculation or 7 days post hospitalization, whichever is later
Primary	Duration of Unsolicited Systemic Symptoms		28 days post virus inoculation or 7 days post hospitalization, whichever is later
Primary	Number of Serious Adverse Events		28 days post virus inoculation or 7 days post hospitalization, whichever is later
Primary	Number of Serious Adverse Events		6 months post virus inoculation
Secondary	Incubation period before onset of fever		Up to 28 days post virus inoculation
Secondary	Viremia by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)		Up to 28 days post virus inoculation
Secondary	Occurrence of fever without other identifiable cause, such as strep throat or influenza	The occurrence of fever defined as greater than or equal to 38°C (100.4° F) measured at least 2 times in 24 hours but not lasting more than 96 hours up to 28 days post virus inoculation without other identifiable cause, such as strep infection or influenza.	Up to 28 days post virus inoculation
Secondary	Occurrence of Headache		Up to 28 days post virus inoculation
Secondary	Grade of Headache		Up to 28 days post virus inoculation
Secondary	Occurrence of Myalgia		Up to 28 days post virus inoculation
Secondary	Grade of Myalgia		Up to 28 days post virus inoculation
Secondary	Occurrence of Rash		Up to 28 days post virus inoculation
Secondary	Grade of Rash		Up to 28 days post virus inoculation
Secondary	Occurrence of Liver Function Tests Abnormalities [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)]		Up to 28 days post virus inoculation
Secondary	Grade of Liver Function Tests Abnormalities [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)]		Up to 28 days post virus inoculation
Secondary	Occurrence of Leukopenia		Up to 28 days post virus inoculation
Secondary	Grade of Leukopenia		Up to 28 days post virus inoculation
Secondary	Occurrence of Thrombocytopenia		Up to 28 days post virus inoculation
Secondary	Grade of Thrombocytopenia		Up to 28 days post virus inoculation