Clinical trial NCT02372175: Assessment of a Dengue-1-Virus-Live Virus Human Challenge - (DENV-1-LVHC) Virus Strain
Official title: Phase One, Open Label, Assessment of a Dengue-1-Virus-Live Virus Human Challenge - (DENV-1-LVHC) Virus Strain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dengue
Keywords: Dengue
Lead sponsor: U.S. Army Medical Research and Development Command
Sponsor class: FED
Collaborators: name: State University of New York - Upstate Medical University
First posted: 2015-02-26
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Abnormal Laboratory Measurements
timeFrame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
measure: Intensity of Abnormal Laboratory Measurements
timeFrame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
measure: Duration of Abnormal Laboratory Measurements
timeFrame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
measure: Occurrence of Solicited Injection Site Symptoms
timeFrame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
measure: Intensity of Solicited Injection Site Symptoms
timeFrame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
measure: Duration of Solicited Injection Site Symptoms
timeFrame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
measure: Occurrence of unsolicited Injection Site Symptoms
timeFrame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
measure: Intensity of Unsolicited Injection Site Symptoms
timeFrame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
measure: Duration of Unsolicited Injection Site Symptoms
timeFrame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
measure: Occurrence of Solicited Systemic Symptoms
timeFrame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
measure: Intensity of Solicited Systemic Symptoms
timeFrame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
measure: Duration of Solicited Systemic Symptoms
timeFrame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
measure: Occurrence of Unsolicited Systemic Symptoms
timeFrame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
measure: Intensity of Unsolicited Systemic Symptoms
timeFrame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
measure: Duration of Unsolicited Systemic Symptoms
timeFrame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
measure: Number of Serious Adverse Events
timeFrame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later
measure: Number of Serious Adverse Events
timeFrame: 6 months post virus inoculation
Secondary outcomes:
measure: Incubation period before onset of fever
timeFrame: Up to 28 days post virus inoculation
measure: Viremia by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)
timeFrame: Up to 28 days post virus inoculation
measure: Occurrence of fever without other identifiable cause, such as strep throat or influenza
timeFrame: Up to 28 days post virus inoculation
measure: Occurrence of Headache
timeFrame: Up to 28 days post virus inoculation
measure: Grade of Headache
timeFrame: Up to 28 days post virus inoculation
measure: Occurrence of Myalgia
timeFrame: Up to 28 days post virus inoculation
measure: Grade of Myalgia
timeFrame: Up to 28 days post virus inoculation
measure: Occurrence of Rash
timeFrame: Up to 28 days post virus inoculation
measure: Grade of Rash
timeFrame: Up to 28 days post virus inoculation
measure: Occurrence of Liver Function Tests Abnormalities [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)]
timeFrame: Up to 28 days post virus inoculation
measure: Grade of Liver Function Tests Abnormalities [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)]
timeFrame: Up to 28 days post virus inoculation
measure: Occurrence of Leukopenia
timeFrame: Up to 28 days post virus inoculation
measure: Grade of Leukopenia
timeFrame: Up to 28 days post virus inoculation
measure: Occurrence of Thrombocytopenia
timeFrame: Up to 28 days post virus inoculation
measure: Grade of Thrombocytopenia
timeFrame: Up to 28 days post virus inoculation
Other outcomes:
Locations:
city: Syracuse
country: United States
facility: State University of New York, Upstate Medical University (SUNY-UMU)
state: New York
Study officials:
affiliation: State University of New York, Upstate Medical University (SUNY-UMU)
name: Timothy P Endy, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Endy TP, Wang D, Polhemus ME, Jarman RG, Jasper LE, Gromowski G, Lin L, De La Barra RA, Friberg H, Currier JR, Abbott M, Ware L, Klick M, Paolino KM, Blair DC, Eckels K, Rutvisuttinunt W, Thomas SJ. A Phase 1, Open-Label Assessment of a Dengue Virus-1 Live Virus Human Challenge Strain. J Infect Dis. 2021 Feb 3;223(2):258-267. doi: 10.1093/infdis/jiaa351.