Expansion of a Dengue-1 Live Virus Human Challenge

Phase One, Open Label Expansion of a Dengue-1-Virus-Live Virus Human Challenge - (DENV-1-LVHC) Virus Strain.

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.

Study Overview

• Status: Completed
• Conditions: Dengue
• Intervention / Treatment: Biological: Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC)

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 Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Syracuse, New York, United States, 13210
      • State University of New York, Upstate Medical University (SUNY-UMU)

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Abnormal Laboratory Parameters	Total number of all abnormal labs	28 days post virus inoculation or 7 days post hospitalization, whichever is later
Intensity of Abnormal Laboratory Parameters	Graded according clinical laboratory normals and FDA toxicity scale	28 days post virus inoculation or 7 days post hospitalization, whichever is later
Duration of Abnormal Laboratory Parameters	Number of days of abnormal lab	28 days post virus inoculation or 7 days post hospitalization, whichever is later
Occurrence of Solicited Injection site symptoms	Number of solicited symptoms	7 days post virus inoculation
Intensity of Solicited Injection site symptoms	Symptoms graded according to FDA toxicity scale	7 days post virus inoculation
Duration of Solicited Injection site symptoms	Number of days per symptom	7 days post virus inoculation
Occurrence of Unsolicited Injection site symptoms	Number of unsolicited site symptoms	28 days post virus inoculation or 7 days post hospitalization, whichever is later
Intensity of Unsolicited Injection site symptoms	Symptoms graded according to FDA toxicity scale	28 days post virus inoculation or 7 days post hospitalization, whichever is later
Duration of Unsolicited Injection site symptoms	Number of days per symptom	28 days post virus inoculation or 7 days post hospitalization, whichever is later
Occurrence of Solicited systemic symptoms	Number of systemic symptoms	28 days post virus inoculation or 7 days post hospitalization, whichever is later
Intensity of Solicited systemic symptoms	Symptoms graded according to FDA toxicity scale	28 days post virus inoculation or 7 days post hospitalization, whichever is later
Duration of Solicited systemic symptoms	Number of days per symptom	28 days post virus inoculation or 7 days post hospitalization, whichever is later
Occurrence of Unsolicited systemic symptoms	Number of symptoms	28 days post virus inoculation or 7 days post hospitalization, whichever is later
Intensity of Unsolicited systemic symptoms	Symptoms graded according to FDA toxicity scale	28 days post virus inoculation or 7 days post hospitalization, whichever is later
Duration of Unsolicited systemic symptoms	Number of days per symptom	28 days post virus inoculation or 7 days post hospitalization, whichever is later
Number of Serious Adverse Events	Total number	28 days post virus inoculation or 7 days post hospitalization, whichever is later
Number of Serious Adverse Events	Total number	6 months post virus inoculation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incubation period before onset of fever	Number of days prior to fever	Up to 28 days post virus inoculation
Viremia by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)	Levels of viremia	Up to 28 days post virus inoculation
Viremia by plaque assay	Quantitation of infectious virus	Up to 28 days post virus inoculation
Occurrence of fever without other identifiable cause, such as strep infection 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 72 hours	Up to 28 days post virus inoculation
Occurrence of Headache	Number of headaches	Up to 28 days post virus inoculation
Grade of Headache	Graded according to FDA toxicity scale	Up to 28 days post virus inoculation
Occurrence of Myalgia	Number of reported myalgias	Up to 28 days post virus inoculation
Grade of Myalgia	Graded according to FDA toxicity scale	Up to 28 days post virus inoculation
Occurrence of Rash	Number of rashes	Up to 28 days post virus inoculation
Grade of Rash	Graded according to FDA toxicity scale	Up to 28 days post virus inoculation
Occurrence of Abnormal Liver Function Test [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)]	Number of abnormal liver function tests	Up to 28 days post virus inoculation
Grade of Abnormal Liver Function Test [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)]	Graded according clinical laboratory normals and FDA toxicity scale	Up to 28 days post virus inoculation
Occurrence of Leukopenia	Number of occurrences	Up to 28 days post virus inoculation
Grade of Leukopenia	Graded according clinical laboratory normals and FDA toxicity scale	Up to 28 days post virus inoculation
Occurrence of Thrombocytopenia	Number of occurrences	Up to 28 days post virus inoculation
Grade of Thrombocytopenia	Graded according clinical laboratory normals and FDA toxicity scale	Up to 28 days post virus inoculation

Collaborators and Investigators

• Sponsor: State University of New York - Upstate Medical University
• Collaborators: U.S. Army Medical Research and Development Command; Janssen Pharmaceutica N.V., Belgium
• Investigators: Principal Investigator: Stephen J Thomas, MD, State University of New York - Upstate Medical University

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2019
• Primary Completion (Actual): September 20, 2019
• Study Completion (Actual): September 20, 2019

Study Registration Dates

• First Submitted: March 5, 2019
• First Submitted That Met QC Criteria: March 7, 2019
• First Posted (Actual): March 11, 2019

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Virus Diseases; Dengue; Flavivirus Infections
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Mosquito-Borne Diseases; Dengue
• Other Study ID Numbers: 2018-01-UMU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No