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Homologous Re-infection With Dengue 1 or Dengue 3

Primary Purpose

Dengue

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Dengue virus 1 Live Virus Human Challenge (DENV-1-LVHC)
Dengue virus 3 Live Virus Human Challenge (DENV-3-LVHC)
Sponsored by
State University of New York - Upstate Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Dengue focused on measuring Dengue, Flavivirus Infections, Virus Diseases

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Age 18-55 at the time of consent Ability and willingness to sign informed consent Passing score on comprehension test of at least 75%, with up to 3 attempts Available for the study period Willing to use contraception for the duration of the study (birth control pills or patches, intrauterine device (IUD), Depo-Provera, implantable birth control (implants of levonorgestrel), estrogenic vaginal ring, tubal ligation, vasectomy of the sole male partner, male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository), male condom combined with a female diaphragm, either with or without vaginal spermicide, partner in a homosexual relationship, abstinence) Provide consent for release of medical history records from primary care physician, college or university, urgent care or emergency room visit Exclusion Criteria: Female: pregnant or lactating 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, endometriosis or uterine scarring Women who intend to become pregnant or men who intend to father a child during the study period (approximately 209 days for Cohorts 1 and 2 and approximately 91 days for Cohorts 3 and 4) Blood tests confirming infection with human immunodeficiency virus- 1 (HIV-1), hepatitis C, hepatitis B (assessed by HbsAg) virus Positive antibodies to dengue (cohorts 1 and 2). If the subject has previously screened negative for dengue in the last 12 months and has not traveled to an endemic area. The results of the previous screening will be used. Any history of dengue infection or dengue vaccination (licensed or experimental) (cohorts 1 and 2); or planned dengue vaccination during the study period (all cohorts) Recent (in the past 4 weeks) travel to any dengue endemic area or travel to a country with risk of yellow fever or Japanese encephalitis transmission Positive urine screen for cocaine, amphetamines, opiates or methadone Currently taking anti-coagulant medication, aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) Active diabetes, active peptic ulcer disease (PUD), chronic obstructive pulmonary disease (COPD), coronary artery disease (CAD) 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) Current, or a history of, auto-immune disease other than well controlled Hashimoto's thyroiditis History of Guillain-Barré syndrome (GBS) 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. 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 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 Planning to donate blood in the 1 year following inoculation with dengue Recent blood donation within prior 14 days of inoculation Receipt of blood products or antibodies within 56 days of inoculation or during the study period Planned travel during the study period (approximately 210 days for Cohorts 1 and 2 and approximately 91 days for Cohorts 3 and 4) which would interfere with the ability to complete all study visits Subjects with the following grade 2 or greater lab abnormalities: Creatinine; ALT, AST; Hemoglobin (females and males); WBC; Platelets; PT; PTT; Fibrinogen Any laboratory abnormalities prior to inoculation that are considered by the investigator to be clinically significant in addition those listed above Significant screening physical examination abnormalities or chronic medical condition that in the opinion of the investigator may impact subject safety Participation (active or follow-up phase) or planned participation in another vaccine, drug, or medical device in the 4 weeks prior to this trial or during the trial Recent or scheduled receipt of any vaccine 4 weeks prior to or after virus inoculation Beliefs that bar the administration of blood products or transfusions Clinician discretion

Sites / Locations

  • State University of New York, Upstate Medical University (SUNY-UMU)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1 Naive DENV1

Cohort 2 Naive DENV3

Cohort 3 Returning DENV1

Cohort 4 Returning DENV3

Arm Description

Dengue-1-Virus-Live-Virus-Human-Challenge (DENV-1-LVHC), two doses (0.5 mL of 6.5 x 10^3 plaque forming units/milliliter (PFU/mL) inoculated subcutaneously on day 1 and day 180.

Dengue-3-Virus-Live-Virus-Human-Challenge (DENV-3-LVHC), two doses (0.5 mL of 1.4 x 10^3 plaque forming units/milliliter (PFU/mL) inoculated subcutaneously on day 1 and day 180.

Dengue-1-Virus-Live-Virus-Human-Challenge (DENV-1-LVHC), single dose (0.5 mL of 6.5 x 10^3 plaque forming units/milliliter (PFU/mL) inoculated subcutaneously on day 1.

Dengue-3-Virus-Live-Virus-Human-Challenge (DENV-3-LVHC), single dose (0.5 mL of 1.4 x 10^3 plaque forming units/milliliter (PFU/mL) inoculated subcutaneously on day 1.

Outcomes

Primary Outcome Measures

Occurrence of Solicited Injection Site Symptoms
Number of solicited symptoms
Intensity of Solicited Injection Site Symptoms
Graded according to FDA Tables for Clinical Abnormalities: Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (severe), Grade 4 (Potentially life threatening)
Duration of Solicited Injection Site Symptoms
Number of days per symptom
Occurrence of Solicited Systemic Symptoms
Number of solicited symptoms
Intensity of Solicited Systemic Symptoms
Graded according to FDA Tables for Clinical Abnormalities: Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (severe), Grade 4 (Potentially life threatening)
Duration of Solicited Systemic Symptoms
Number of days per symptom
Occurrence of Unsolicited Systemic Symptoms
Number of unsolicited symptom
Intensity of Unsolicited Systemic Symptoms
Graded according to FDA Tables for Clinical Abnormalities: Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (severe), Grade 4 (Potentially life threatening)
Duration of Unsolicited Systemic Symptoms
Number of days per symptom
Number of Abnormal Laboratory Measurements
Total number of all abnormal labs
Intensity of Abnormal Laboratory Measurements
Graded according to SUNY Upstate clinical laboratory normals and FDA Tables for Laboratory Abnormalities: Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (severe), Grade 4 (Potentially life threatening)
Duration of Abnormal Laboratory Measurements
Number of days of abnormal labs
Number of Serious Adverse Events
Total number
Number of Serious Adverse Events
Total number
Number of Serious Adverse Events
Total number

Secondary Outcome Measures

Full Information

First Posted
July 21, 2023
Last Updated
October 16, 2023
Sponsor
State University of New York - Upstate Medical University
Collaborators
U.S. Army Medical Research and Development Command, Walter Reed Army Institute of Research (WRAIR)
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1. Study Identification

Unique Protocol Identification Number
NCT05967455
Brief Title
Homologous Re-infection With Dengue 1 or Dengue 3
Official Title
Phase One, Open Label, Homologous Reinfection With Dengue-1-Virus-Live Virus Human Challenge - (DENV-1-LVHC) or Dengue-3-Virus-Live Virus Human Challenge (DENV-3-LVHC) Virus Strains
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
State University of New York - Upstate Medical University
Collaborators
U.S. Army Medical Research and Development Command, Walter Reed Army Institute of Research (WRAIR)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Previous studies with one dengue infection in a controlled environment at Upstate generated data that has been important in understanding the clinical signs and symptoms and how a person's body reacts to dengue infection over time. This has helped investigators compare what is seen in the clinic to what is seen in areas where dengue is prevalent. The investigators want to collect similar information when a person gets the same dengue twice in a controlled environment with the hope that this will lead them to a better understanding of the disease. New participants will receive one inoculation of dengue and then return to the clinic or be contacted by phone over 6 months; will receive a second inoculation after 6 months and return to the clinic or be contacted by phone for one more month; will collect saliva at home; will allow the study team to collect blood and saliva at the clinic visits. Participants who have been in previous dengue inoculation studies at SUNY Upstate will receive one inoculation of dengue and then return to the clinic or be contacted by phone over 3 months; will collect saliva at home; will allow the study team to collect blood and saliva at the clinic visits. All participants will be seen in the clinic every other day for the first three weeks after any inoculation.
Detailed Description
The purpose of this study is to explore the clinical, virologic, and immunologic response of subjects following primary controlled dengue infection or following controlled homologous dengue reinfection. SUNY Upstate Medical University completed three Dengue Human Infection Model studies, two with dengue 1 (DENV-1-LVHC), NCT 02372175 and NCT 03869060, and one with dengue 3 (DENV-3-LVHC), NCT 04298138 and investigators gained incredible knowledge about primary dengue infection. The investigators are moving to the next step in acquiring knowledge about the kinetics of homologous secondary infection in a controlled setting in this study. People who acquire natural dengue infection and who are subsequently infected by the same serotype are thought to have lifelong protection to that serotype. Investigators will recruit up to 10 naive participants and infect them with either DENV-1-LVHC or DENV-3-LVHC with the same dose of virus as in previous studies. These participants will be followed over 6 months and reinfected with the same serotype originally received, i.e. homologous reinfection, and followed for another three months. Investigators will also recruit up to 10 participants who received either DENV-1-LVHC or DENV-3-LVHC in previous studies. These participants will be reinfected with the same serotype that was previously received and followed for 6 months. Investigators intend to collect similar information about the kinetics of homologous secondary infection as was collected in the studies following primary infection.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dengue
Keywords
Dengue, Flavivirus Infections, Virus Diseases

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1 Naive DENV1
Arm Type
Experimental
Arm Description
Dengue-1-Virus-Live-Virus-Human-Challenge (DENV-1-LVHC), two doses (0.5 mL of 6.5 x 10^3 plaque forming units/milliliter (PFU/mL) inoculated subcutaneously on day 1 and day 180.
Arm Title
Cohort 2 Naive DENV3
Arm Type
Experimental
Arm Description
Dengue-3-Virus-Live-Virus-Human-Challenge (DENV-3-LVHC), two doses (0.5 mL of 1.4 x 10^3 plaque forming units/milliliter (PFU/mL) inoculated subcutaneously on day 1 and day 180.
Arm Title
Cohort 3 Returning DENV1
Arm Type
Experimental
Arm Description
Dengue-1-Virus-Live-Virus-Human-Challenge (DENV-1-LVHC), single dose (0.5 mL of 6.5 x 10^3 plaque forming units/milliliter (PFU/mL) inoculated subcutaneously on day 1.
Arm Title
Cohort 4 Returning DENV3
Arm Type
Experimental
Arm Description
Dengue-3-Virus-Live-Virus-Human-Challenge (DENV-3-LVHC), single dose (0.5 mL of 1.4 x 10^3 plaque forming units/milliliter (PFU/mL) inoculated subcutaneously on day 1.
Intervention Type
Biological
Intervention Name(s)
Dengue virus 1 Live Virus Human Challenge (DENV-1-LVHC)
Intervention Description
Dengue subtype 1 Challenge Virus (DENV-1) strain 45AZ5
Intervention Type
Biological
Intervention Name(s)
Dengue virus 3 Live Virus Human Challenge (DENV-3-LVHC)
Intervention Description
Dengue subtype 3 Challenge Virus (DENV-3) strain CH53489
Primary Outcome Measure Information:
Title
Occurrence of Solicited Injection Site Symptoms
Description
Number of solicited symptoms
Time Frame
6 days post virus inoculation
Title
Intensity of Solicited Injection Site Symptoms
Description
Graded according to FDA Tables for Clinical Abnormalities: Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (severe), Grade 4 (Potentially life threatening)
Time Frame
6 days post virus inoculation
Title
Duration of Solicited Injection Site Symptoms
Description
Number of days per symptom
Time Frame
6 days post virus inoculation
Title
Occurrence of Solicited Systemic Symptoms
Description
Number of solicited symptoms
Time Frame
20 day post primary infection for cohorts 1 and 2 and 20 days post reinfection, all cohorts
Title
Intensity of Solicited Systemic Symptoms
Description
Graded according to FDA Tables for Clinical Abnormalities: Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (severe), Grade 4 (Potentially life threatening)
Time Frame
20 day post primary infection, cohorts 1 and 2 and 20 days post reinfection, all cohorts
Title
Duration of Solicited Systemic Symptoms
Description
Number of days per symptom
Time Frame
20 day post primary infection, cohorts 1 and 2 and 20 days post reinfection, all cohorts
Title
Occurrence of Unsolicited Systemic Symptoms
Description
Number of unsolicited symptom
Time Frame
28 day post primary infection, cohorts 1 and 2 and 28 days post reinfection, all cohorts
Title
Intensity of Unsolicited Systemic Symptoms
Description
Graded according to FDA Tables for Clinical Abnormalities: Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (severe), Grade 4 (Potentially life threatening)
Time Frame
28 day post primary infection, cohorts 1 and 2 and 28 days post reinfection, all cohorts
Title
Duration of Unsolicited Systemic Symptoms
Description
Number of days per symptom
Time Frame
28 day post primary infection, cohorts 1 and 2 and 28 days post reinfection, all cohorts
Title
Number of Abnormal Laboratory Measurements
Description
Total number of all abnormal labs
Time Frame
28 day post primary infection, cohorts 1 and 2 and 28 days post reinfection, all cohorts
Title
Intensity of Abnormal Laboratory Measurements
Description
Graded according to SUNY Upstate clinical laboratory normals and FDA Tables for Laboratory Abnormalities: Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (severe), Grade 4 (Potentially life threatening)
Time Frame
28 day post primary infection, cohorts 1 and 2 and 28 days post reinfection, all cohorts
Title
Duration of Abnormal Laboratory Measurements
Description
Number of days of abnormal labs
Time Frame
28 day post primary infection, cohorts 1 and 2 and 28 days post reinfection, all cohorts
Title
Number of Serious Adverse Events
Description
Total number
Time Frame
6 months post primary infection, cohorts 1 and 2
Title
Number of Serious Adverse Events
Description
Total number
Time Frame
3 months post reinfection, cohorts 1 and 2
Title
Number of Serious Adverse Events
Description
Total number
Time Frame
6 months post reinfection, cohorts 3 and 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Age 18-55 at the time of consent Ability and willingness to sign informed consent Passing score on comprehension test of at least 75%, with up to 3 attempts Available for the study period Willing to use contraception for the duration of the study (birth control pills or patches, intrauterine device (IUD), Depo-Provera, implantable birth control (implants of levonorgestrel), estrogenic vaginal ring, tubal ligation, vasectomy of the sole male partner, male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository), male condom combined with a female diaphragm, either with or without vaginal spermicide, partner in a homosexual relationship, abstinence) Provide consent for release of medical history records from primary care physician, college or university, urgent care or emergency room visit Exclusion Criteria: Female: pregnant or lactating 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, endometriosis or uterine scarring Women who intend to become pregnant or men who intend to father a child during the study period (approximately 209 days for Cohorts 1 and 2 and approximately 91 days for Cohorts 3 and 4) Blood tests confirming infection with human immunodeficiency virus- 1 (HIV-1), hepatitis C, hepatitis B (assessed by HbsAg) virus Positive antibodies to dengue (cohorts 1 and 2). If the subject has previously screened negative for dengue in the last 12 months and has not traveled to an endemic area. The results of the previous screening will be used. Any history of dengue infection or dengue vaccination (licensed or experimental) (cohorts 1 and 2); or planned dengue vaccination during the study period (all cohorts) Recent (in the past 4 weeks) travel to any dengue endemic area or travel to a country with risk of yellow fever or Japanese encephalitis transmission Positive urine screen for cocaine, amphetamines, opiates or methadone Currently taking anti-coagulant medication, aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) Active diabetes, active peptic ulcer disease (PUD), chronic obstructive pulmonary disease (COPD), coronary artery disease (CAD) 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) Current, or a history of, auto-immune disease other than well controlled Hashimoto's thyroiditis History of Guillain-Barré syndrome (GBS) 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. 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 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 Planning to donate blood in the 1 year following inoculation with dengue Recent blood donation within prior 14 days of inoculation Receipt of blood products or antibodies within 56 days of inoculation or during the study period Planned travel during the study period (approximately 210 days for Cohorts 1 and 2 and approximately 91 days for Cohorts 3 and 4) which would interfere with the ability to complete all study visits Subjects with the following grade 2 or greater lab abnormalities: Creatinine; ALT, AST; Hemoglobin (females and males); WBC; Platelets; PT; PTT; Fibrinogen Any laboratory abnormalities prior to inoculation that are considered by the investigator to be clinically significant in addition those listed above Significant screening physical examination abnormalities or chronic medical condition that in the opinion of the investigator may impact subject safety Participation (active or follow-up phase) or planned participation in another vaccine, drug, or medical device in the 4 weeks prior to this trial or during the trial Recent or scheduled receipt of any vaccine 4 weeks prior to or after virus inoculation Beliefs that bar the administration of blood products or transfusions Clinician discretion
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Keely Terrillion
Phone
315-464-9869
Email
Trials@upstate.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen J Thomas, MD
Organizational Affiliation
State University of New York - Upstate Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
State University of New York, Upstate Medical University (SUNY-UMU)
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa Ware, MS
Phone
315-464-4398
Email
warel@upstate.edu

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32572470
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.
Results Reference
result
PubMed Identifier
36288280
Citation
Waickman AT, Lu JQ, Fang H, Waldran MJ, Gebo C, Currier JR, Ware L, Van Wesenbeeck L, Verpoorten N, Lenz O, Tambuyzer L, Herrera-Taracena G, Van Loock M, Endy TP, Thomas SJ. Evolution of inflammation and immunity in a dengue virus 1 human infection model. Sci Transl Med. 2022 Oct 26;14(668):eabo5019. doi: 10.1126/scitranslmed.abo5019. Epub 2022 Oct 26.
Results Reference
result

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Homologous Re-infection With Dengue 1 or Dengue 3

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