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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02372175
First Posted: February 26, 2015
Last Update Posted: October 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
State University of New York - Upstate Medical University
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command
  Purpose
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.

Condition Intervention Phase
Dengue Biological: Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC) Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Phase One, Open Label, Assessment of a Dengue-1-Virus-Live Virus Human Challenge - (DENV-1-LVHC) Virus Strain

Resource links provided by NLM:


Further study details as provided by U.S. Army Medical Research and Materiel Command:

Primary Outcome Measures:
  • Number of Abnormal Laboratory Measurements [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
  • Intensity of Abnormal Laboratory Measurements [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
  • Duration of Abnormal Laboratory Measurements [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
  • Occurrence of Solicited Injection Site Symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
  • Intensity of Solicited Injection Site Symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
  • Duration of Solicited Injection Site Symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
  • Occurrence of unsolicited Injection Site Symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
  • Intensity of Unsolicited Injection Site Symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
  • Duration of Unsolicited Injection Site Symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
  • Occurrence of Solicited Systemic Symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
  • Intensity of Solicited Systemic Symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
  • Duration of Solicited Systemic Symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
  • Occurrence of Unsolicited Systemic Symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
  • Intensity of Unsolicited Systemic Symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
  • Duration of Unsolicited Systemic Symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
  • Number of Serious Adverse Events [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
  • Number of Serious Adverse Events [ Time Frame: 6 months post virus inoculation ]

Secondary Outcome Measures:
  • Incubation period before onset of fever [ Time Frame: Up to 28 days post virus inoculation ]
  • Viremia by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) [ Time Frame: Up to 28 days post virus inoculation ]
  • Occurrence of fever without other identifiable cause, such as strep throat or influenza [ Time Frame: 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 96 hours up to 28 days post virus inoculation without other identifiable cause, such as strep infection or influenza.

  • Occurrence of Headache [ Time Frame: Up to 28 days post virus inoculation ]
  • Grade of Headache [ Time Frame: Up to 28 days post virus inoculation ]
  • Occurrence of Myalgia [ Time Frame: Up to 28 days post virus inoculation ]
  • Grade of Myalgia [ Time Frame: Up to 28 days post virus inoculation ]
  • Occurrence of Rash [ Time Frame: Up to 28 days post virus inoculation ]
  • Grade of Rash [ Time Frame: Up to 28 days post virus inoculation ]
  • Occurrence of Liver Function Tests Abnormalities [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] [ Time Frame: Up to 28 days post virus inoculation ]
  • Grade of Liver Function Tests Abnormalities [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] [ Time Frame: Up to 28 days post virus inoculation ]
  • Occurrence of Leukopenia [ Time Frame: Up to 28 days post virus inoculation ]
  • Grade of Leukopenia [ Time Frame: Up to 28 days post virus inoculation ]
  • Occurrence of Thrombocytopenia [ Time Frame: Up to 28 days post virus inoculation ]
  • Grade of Thrombocytopenia [ Time Frame: Up to 28 days post virus inoculation ]

Estimated Enrollment: 27
Study Start Date: October 2015
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Low dose DENV-1-LVHC
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)
Dengue subtype 1 Challenge Virus (DENV-1) strain 45AZ5 administered as a single injection.
Experimental: Medium dose DENV-1-LVHC
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)
Dengue subtype 1 Challenge Virus (DENV-1) strain 45AZ5 administered as a single injection.
Experimental: High dose DENV-1-LVHC
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)
Dengue subtype 1 Challenge Virus (DENV-1) strain 45AZ5 administered as a single injection.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02372175


Locations
United States, New York
State University of New York, Upstate Medical University (SUNY-UMU)
Syracuse, New York, United States, 13210
Sponsors and Collaborators
U.S. Army Medical Research and Materiel Command
State University of New York - Upstate Medical University
Investigators
Principal Investigator: Timothy P Endy, MD, MPH State University of New York, Upstate Medical University (SUNY-UMU)
  More Information

Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT02372175     History of Changes
Other Study ID Numbers: S-14-09
First Submitted: February 10, 2015
First Posted: February 26, 2015
Last Update Posted: October 12, 2017
Last Verified: October 2017

Keywords provided by U.S. Army Medical Research and Materiel Command:
Dengue

Additional relevant MeSH terms:
Dengue
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral