Expansion of a Dengue-1 Live Virus Human Challenge

Phase 1

Completed

• Conditions: Dengue
• Interventions: Biological: Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC)

• Registration Number: NCT03869060
• Lead Sponsor: State University of New York - Upstate Medical University

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.

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 Timeline

• Study First Submitted: 2019-03-05
• Study First Submitted QC: 2019-03-07
• Study Start: 2019-03-11
• Study First Posted: 2019-03-11
• Primary Completion: 2019-09-20
• Study Completion: 2019-09-20
• Status Verified: 2020-01
• Last Update Submitted: 2024-04-09
• Last Update Posted: 2024-04-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Inoculated Group	Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC)	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

State University of New York, Upstate Medical University (SUNY-UMU); 🇺🇸 Syracuse, New York, United States