Expansion of a Dengue-1 Live Virus Human Challenge

• ClinicalTrials.gov Identifier: NCT03869060
• Recruitment Status: Completed
• First Posted: March 11, 2019
• Last Update Posted: January 6, 2020
• Sponsor: State University of New York - Upstate Medical University
• Collaborators: Janssen Pharmaceutica N.V., Belgium; U.S. Army Medical Research and Development Command
• Information provided by (Responsible Party): State University of New York - Upstate Medical University

Study Description

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.

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

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Phase One, Open Label Expansion of a Dengue-1-Virus-Live Virus Human Challenge - (DENV-1-LVHC) Virus Strain.
• Actual Study Start Date: February 4, 2019
• Actual Primary Completion Date: September 20, 2019
• Actual Study Completion Date: September 20, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Inoculated Group; Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC) given as a single 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

Outcome Measures

Primary Outcome Measures :

1. Number of Abnormal Laboratory Parameters [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
   Total number of all abnormal labs
2. Intensity of Abnormal Laboratory Parameters [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
   Graded according clinical laboratory normals and FDA toxicity scale
3. Duration of Abnormal Laboratory Parameters [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
   Number of days of abnormal lab
4. Occurrence of Solicited Injection site symptoms [ Time Frame: 7 days post virus inoculation ]
   Number of solicited symptoms
5. Intensity of Solicited Injection site symptoms [ Time Frame: 7 days post virus inoculation ]
   Symptoms graded according to FDA toxicity scale
6. Duration of Solicited Injection site symptoms [ Time Frame: 7 days post virus inoculation ]
   Number of days per symptom
7. Occurrence of Unsolicited Injection site symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
   Number of unsolicited site symptoms
8. Intensity of Unsolicited Injection site symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
   Symptoms graded according to FDA toxicity scale
9. Duration of Unsolicited Injection site symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
   Number of days per symptom
10. Occurrence of Solicited systemic symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
    Number of systemic symptoms
11. Intensity of Solicited systemic symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
    Symptoms graded according to FDA toxicity scale
12. Duration of Solicited systemic symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
    Number of days per symptom
13. Occurrence of Unsolicited systemic symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
    Number of symptoms
14. Intensity of Unsolicited systemic symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
    Symptoms graded according to FDA toxicity scale
15. Duration of Unsolicited systemic symptoms [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
    Number of days per symptom
16. Number of Serious Adverse Events [ Time Frame: 28 days post virus inoculation or 7 days post hospitalization, whichever is later ]
    Total number
17. Number of Serious Adverse Events [ Time Frame: 6 months post virus inoculation ]
    Total number

Secondary Outcome Measures :

1. Incubation period before onset of fever [ Time Frame: Up to 28 days post virus inoculation ]
   Number of days prior to fever
2. Viremia by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) [ Time Frame: Up to 28 days post virus inoculation ]
   Levels of viremia
3. Viremia by plaque assay [ Time Frame: Up to 28 days post virus inoculation ]
   Quantitation of infectious virus
4. Occurrence of fever without other identifiable cause, such as strep infection 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 72 hours
5. Occurrence of Headache [ Time Frame: Up to 28 days post virus inoculation ]
   Number of headaches
6. Grade of Headache [ Time Frame: Up to 28 days post virus inoculation ]
   Graded according to FDA toxicity scale
7. Occurrence of Myalgia [ Time Frame: Up to 28 days post virus inoculation ]
   Number of reported myalgias
8. Grade of Myalgia [ Time Frame: Up to 28 days post virus inoculation ]
   Graded according to FDA toxicity scale
9. Occurrence of Rash [ Time Frame: Up to 28 days post virus inoculation ]
   Number of rashes
10. Grade of Rash [ Time Frame: Up to 28 days post virus inoculation ]
    Graded according to FDA toxicity scale
11. Occurrence of Abnormal Liver Function Test [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] [ Time Frame: Up to 28 days post virus inoculation ]
    Number of abnormal liver function tests
12. Grade of Abnormal Liver Function Test [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] [ Time Frame: Up to 28 days post virus inoculation ]
    Graded according clinical laboratory normals and FDA toxicity scale
13. Occurrence of Leukopenia [ Time Frame: Up to 28 days post virus inoculation ]
    Number of occurrences
14. Grade of Leukopenia [ Time Frame: Up to 28 days post virus inoculation ]
    Graded according clinical laboratory normals and FDA toxicity scale
15. Occurrence of Thrombocytopenia [ Time Frame: Up to 28 days post virus inoculation ]
    Number of occurrences
16. Grade of Thrombocytopenia [ Time Frame: Up to 28 days post virus inoculation ]
    Graded according clinical laboratory normals and FDA toxicity scale

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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 exclusion criteria 16
16. Subjects with the following grade 1 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
17. Significant screening physical examination abnormalities at the discretion of the investigator
18. Women who intend to become pregnant or men who intend to father a child during the study period (approximately 180 days)
19. 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
20. Planning to donate blood in the 1 year following inoculation with dengue
21. Recent blood donation within prior 56 days of inoculation
22. Receipt of blood products or antibodies within 56 days of inoculation or during the study period
23. 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
24. Recent or scheduled receipt of any vaccine 4 weeks prior to or after virus inoculation
25. Beliefs that bar the administration of blood products or transfusions
26. Positive urine screen for cocaine, amphetamines, or opiates
27. Currently taking Methadone or Suboxone
28. Currently taking anti-coagulant medication, aspirin or non-steroidal anti-inflammatory drugs (NSAIDs)
29. 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
30. Chronic medical condition that, in the opinion of the investigator, impacts subject safety.

Contacts and Locations

Locations

United States, New York

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

Janssen Pharmaceutica N.V., Belgium

U.S. Army Medical Research and Development Command

Investigators

• Principal Investigator: Stephen J Thomas, MD; State University of New York - Upstate Medical University

More Information

• Responsible Party: State University of New York - Upstate Medical University
• ClinicalTrials.gov Identifier: NCT03869060
• Other Study ID Numbers: 2018-01-UMU
• First Posted: March 11, 2019
• Last Update Posted: January 6, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by State University of New York - Upstate Medical University:

Dengue; Flavivirus Infections; Virus Diseases

Additional relevant MeSH terms:

Dengue; Arbovirus Infections; Vector Borne Diseases; Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral