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 supports the expansion of the data set of the current Dengue 1 Live Virus Human Challenge (DENV-1-LVHC) model to produce uncomplicated dengue-like illness.
Detailed description
This is an expansion of a previous study conducted under NCT02372175. In this study up to nine healthy subjects between 18 and 45 years old will be inoculated with Dengue 1 Live Virus Human Challenge (DENV-1-LVHC) at a dose used in the previous 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 assess. The goal is to expand the data set of symptoms produced by uncomplicated dengue-like illness.
Interventions
Dengue subtype 1 Challenge Virus (DENV-1) strain 45AZ5
Sponsors
Janssen Pharmaceutica N.V., Belgium
U.S. Army Medical Research and Development Command
State University of New York - Upstate Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
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 grade 2 laboratory abnormalities prior to inoculation for the tests specified in Table 18 and Table 19 of the protocol, except those listed in
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Unsolicited systemic symptoms | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | Number of symptoms |
| Duration of Solicited systemic symptoms | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | Number of days per symptom |
| Intensity of Unsolicited systemic symptoms | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | Symptoms 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 |
| Number of Serious Adverse Events | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | Total number |
| Number of Abnormal Laboratory Parameters | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | Total number of all abnormal labs |
| Intensity of Abnormal Laboratory Parameters | 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 Parameters | 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 | Symptoms 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 | Symptoms 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 systemic symptoms |
| Intensity of Solicited systemic symptoms | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | Symptoms graded according to FDA toxicity scale |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Viremia by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) | Up to 28 days post virus inoculation | Levels of viremia |
| Viremia by plaque assay | Up to 28 days post virus inoculation | Quantitation of infectious virus |
| Occurrence of fever without other identifiable cause, such as strep infection or influenza | Up to 28 days post virus inoculation | 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 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 |
Countries
United States
Outcome results
None listed