Dengue
Conditions
Keywords
Dengue, Flavivirus Infections, Virus Diseases
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.
Interventions
Dengue subtype 3 Challenge Virus (DENV-3) strain CH53489 administered as a single injection.
Sponsors
Walter Reed Army Institute of Research (WRAIR)
U.S. Army Medical Research and Development Command
State University of New York - Upstate Medical University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Nine subjects will be assigned to the low dose group. Twenty-one days post inoculation, data will be reviewed for safety and if performance parameters are met. If safety profile is acceptable but performance parameters have not been met, dose escalation to the medium dose will proceed in nine additional subjects. Twenty-one days post middle dose inoculation, data will be reviewed as above and a determination will be made to proceed to the high dose.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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 15. Any laboratory abnormalities prior to inoculation for the tests specified in Table 18 and Table 19 of the protocol, that are considered by the investigator to be clinically significant except those listed in
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Serious Adverse Events | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | Total number |
| Number of Abnormal Laboratory Measurements | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | Total number of all abnormal labs |
| Intensity of Abnormal Laboratory Measurements | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | Graded according clinical laboratory normals and FDA toxicity scale |
| Duration of Abnormal Laboratory Measurements | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | Number of days of abnormal lab |
| Occurrence of Solicited Injection Site Symptoms | 7 days post virus inoculation | Number of solicited symptoms |
| Intensity of Solicited Injection Site Symptoms | 7 days post virus inoculation | Graded according to FDA toxicity scale |
| Duration of Solicited Injection Site Symptoms | 7 days post virus inoculation | Number of days per symptom |
| Occurrence of Unsolicited Injection Site Symptoms | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | Number of unsolicited site symptoms |
| Intensity of Unsolicited Injection Site Symptoms | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | Graded according to FDA toxicity scale |
| Duration of Unsolicited Injection Site Symptoms | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | Number of days per symptom |
| Occurrence of Solicited Systemic Symptoms | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | Number of solicited systemic symptoms |
| Intensity of Solicited Systemic Symptoms | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | Graded according to FDA toxicity scale |
| Duration of Solicited Systemic Symptoms | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | Number of days per symptom |
| Occurence of Unsolicited Systemic Symptoms | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | Number of unsolicited systemic symptoms |
| Intensity of Unsolicited Systemic Symptoms | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | Graded according to FDA toxicity scale |
| Duration of Unsolicited Systemic Symptoms | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | Number of days per symptom |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Viremia by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) | Up to 28 days post virus inoculation | Levels of viremia |
| Occurence of fever | Up to 28 days post virus inoculation | 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 72 hours |
| Occurrence of Headache | Up to 28 days post virus inoculation | Number of headaches |
| Grade of Headache | Up to 28 days post virus inoculation | Graded according to FDA toxicity scale |
| Occurrence of Myalgia | Up to 28 days post virus inoculation | Number of reported myalgias |
| Grade of Myalgia | Up to 28 days post virus inoculation | Graded according to FDA toxicity scale |
| Occurrence of Rash | Up to 28 days post virus inoculation | Number of rashes |
| Grade of Rash | Up to 28 days post virus inoculation | Graded according to FDA toxicity scale |
| Occurrence of Abnormal Liver Function Test [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] | Up to 28 days post virus inoculation | Number of abnormal liver function tests |
| Grade of Abnormal Liver Function Test [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] | Up to 28 days post virus inoculation | Graded according clinical laboratory normals and FDA toxicity scale |
| Occurrence of Leukopenia | Up to 28 days post virus inoculation | Number of occurrences |
| Grade of Leukopenia | Up to 28 days post virus inoculation | Graded according clinical laboratory normals and FDA toxicity scale |
| Occurrence of Thrombocytopenia | Up to 28 days post virus inoculation | Number of occurrences |
| Grade of Thrombocytopenia | Up to 28 days post virus inoculation | Graded according clinical laboratory normals and FDA toxicity scale |
| Incubation period before onset of fever | Up to 28 days post virus inoculation | Number of days prior to fever |
Countries
United States
Outcome results
None listed