Dengue 3 Human Infection Model (DENV-3)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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 |
Biological: Dengue virus 3 Live Virus Human Challenge (DENV-3-LVHC)
Dengue subtype 3 Challenge Virus (DENV-3) strain CH53489 administered as a single injection.
|
| Experimental: 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 |
Biological: Dengue virus 3 Live Virus Human Challenge (DENV-3-LVHC)
Dengue subtype 3 Challenge Virus (DENV-3) strain CH53489 administered as a single injection.
|
| Experimental: 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 |
Biological: Dengue virus 3 Live Virus Human Challenge (DENV-3-LVHC)
Dengue subtype 3 Challenge Virus (DENV-3) strain CH53489 administered as a single injection.
|
Outcome Measures
Primary Outcome Measures
- 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
- Number of Serious Adverse Events [28 days post virus inoculation or 7 days post hospitalization, whichever is later]
Total number
- Number of Serious Adverse Events [6 months post virus inoculation]
Total number
Secondary Outcome Measures
- 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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age 18-45 at the time of consent
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Ability and willingness to sign informed consent
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Passing score on comprehension test of at least 75%, with up to 3 attempts
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Available for the study period
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Willing to use contraception for the duration of the study
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Provide consent for release of medical history records from primary care physician, college or university, urgent care or emergency room visit
Exclusion Criteria:
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Female: pregnant or lactating
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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.
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Female subjects using an intrauterine device (IUD) or Mirena®
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Female subjects with fibroids or uterine polyps, endometriosis, adenomyosis, and uterine scarring (e.g., after D&C)
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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.
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Active Diabetes or active peptic ulcer disease (PUD)
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Chronic obstructive pulmonary disease (COPD) or coronary artery disease (CAD)
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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)
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Current, or a history of, auto-immune disease
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History of Guillain-Barré syndrome (GBS)
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Any history of FV infection or FV vaccination; or planned FV vaccination, outside the study protocol, during the study period
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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.
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Planned travel during the study period (180 days) which would interfere with the ability to complete all study visits
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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
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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 exclusion criteria 16
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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
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Significant screening physical examination abnormalities at the discretion of the investigator
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Women who intend to become pregnant or men who intend to father a child during the study period (approximately 180 days)
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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
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Planning to donate blood in the 1 year following inoculation with dengue
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Recent blood donation within prior 56 days of inoculation
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Receipt of blood products or antibodies within 56 days of inoculation or during the study period
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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
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Recent or scheduled receipt of any vaccine 4 weeks prior to or after virus inoculation
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Beliefs that bar the administration of blood products or transfusions
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Positive urine screen for cocaine, amphetamines, or opiates
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Currently taking Methadone or Suboxone
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Currently taking anti-coagulant medication, aspirin or non-steroidal anti-inflammatory drugs (NSAIDs)
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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
-
Chronic medical condition that, in the opinion of the investigator, impacts subject safety.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | State University of New York, Upstate Medical University (SUNY-UMU) | Syracuse | New York | United States | 13210 |
Sponsors and Collaborators
- State University of New York - Upstate Medical University
- Walter Reed Army Institute of Research (WRAIR)
- U.S. Army Medical Research and Development Command
Investigators
- Principal Investigator: Stephen J Thomas, MD, State University of New York, Upstate Medical University (SUNY-UMU)
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2019-01-UMU