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

Study Overview
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Brief Summary
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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.

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

Conditions
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Dengue

Intervention / Treatment
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* Biological: Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, male or non-pregnant, non-lactating female Age 18-45 Ability and willingness to sign informed consent Passing score on comprehension test would be 75%, with up to 3 attempts Available for the study period Willing to use contraception for the duration of the study. Provide consent for release of medical history records from primary care physician, college or university, urgent care or emergency room visit Exclusion Criteria: Female: pregnant or lactating 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. Female subjects using an intrauterine device (IUD) or Mirena® Female subjects with fibroids or uterine polyps, endometriosis, dysmenorrhea, adenomyosis, and uterine scarring (e.g. after D&C) 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. Diabetes, chronic obstructive pulmonary disease (COPD), peptic ulcer disease (PUD), or coronary artery disease (CAD) 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) Immediate family member (e.g. parent, sibling, child) with current, or a history of immunodeficiency or autoimmune disease Current or a history of auto-immune disease History of Guillain Barré syndrome (GBS) Any history of FV infection or FV vaccination; or planned FV vaccination, outside the study protocol, during the study period 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. Planned travel during the study period (180 days) which would interfere with the ability to complete all study visits 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 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 Significant screening physical examination abnormalities at the discretion of the investigator Women who intend to become pregnant or men who intend to father a child during the study period (approximately 6 months) 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 Planning to donate blood in the 1 year following inoculation with dengue 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 Beliefs that bar the administration of blood products or transfusions Positive urine screen for cocaine, amphetamines, or opiates Currently taking Methadone or Suboxone Currently taking anti-coagulant medication, aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) 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 Chronic medical condition that, in the opinion of the investigator impacts subject safety.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose DENV-1-LVHC<br>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 | Biological: Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC)<br>* Dengue subtype 1 Challenge Virus (DENV-1) strain 45AZ5 administered as a single injection.<br>|
| Experimental: Medium dose DENV-1-LVHC<br>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 | Biological: Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC)<br>* Dengue subtype 1 Challenge Virus (DENV-1) strain 45AZ5 administered as a single injection.<br>|
| Experimental: High dose DENV-1-LVHC<br>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 | Biological: Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC)<br>* Dengue subtype 1 Challenge Virus (DENV-1) strain 45AZ5 administered as a single injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Abnormal Laboratory Measurements |  | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | 
| Intensity of Abnormal Laboratory Measurements |  | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | 
| Duration of Abnormal Laboratory Measurements |  | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | 
| Occurrence of Solicited Injection Site Symptoms |  | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | 
| Intensity of Solicited Injection Site Symptoms |  | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | 
| Duration of Solicited Injection Site Symptoms |  | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | 
| Occurrence of unsolicited Injection Site Symptoms |  | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | 
| Intensity of Unsolicited Injection Site Symptoms |  | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | 
| Duration of Unsolicited Injection Site Symptoms |  | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | 
| Occurrence of Solicited Systemic Symptoms |  | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | 
| Intensity of Solicited Systemic Symptoms |  | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | 
| Duration of Solicited Systemic Symptoms |  | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | 
| Occurrence of Unsolicited Systemic Symptoms |  | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | 
| Intensity of Unsolicited Systemic Symptoms |  | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | 
| Duration of Unsolicited Systemic Symptoms |  | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | 
| Number of Serious Adverse Events |  | 28 days post virus inoculation or 7 days post hospitalization, whichever is later | 
| Number of Serious Adverse Events |  | 6 months post virus inoculation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incubation period before onset of fever |  | Up to 28 days post virus inoculation | 
| Viremia by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) |  | Up to 28 days post virus inoculation | 
| 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 | 
| Occurrence of Headache |  | Up to 28 days post virus inoculation | 
| Grade of Headache |  | Up to 28 days post virus inoculation | 
| Occurrence of Myalgia |  | Up to 28 days post virus inoculation | 
| Grade of Myalgia |  | Up to 28 days post virus inoculation | 
| Occurrence of Rash |  | Up to 28 days post virus inoculation | 
| Grade of Rash |  | Up to 28 days post virus inoculation | 
| Occurrence of Liver Function Tests Abnormalities [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] |  | Up to 28 days post virus inoculation | 
| Grade of Liver Function Tests Abnormalities [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] |  | Up to 28 days post virus inoculation | 
| Occurrence of Leukopenia |  | Up to 28 days post virus inoculation | 
| Grade of Leukopenia |  | Up to 28 days post virus inoculation | 
| Occurrence of Thrombocytopenia |  | Up to 28 days post virus inoculation | 
| Grade of Thrombocytopenia |  | Up to 28 days post virus inoculation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dengue