Homologous Re-infection With Dengue 1 or Dengue 3

NCT05967455 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 2023-01-UMU
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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 three more months;
• 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 6 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.

Conditions

Dengue

Keywords

Dengue; Flavivirus Infections; Virus Diseases

Outcome Measures

Primary Outcomes (15)

• Occurrence of Solicited Injection Site Symptoms

  Number of solicited symptoms

  6 days post virus inoculation

• 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)

  6 days post virus inoculation

• Duration of Solicited Injection Site Symptoms

  Number of days per symptom

  6 days post virus inoculation

• Occurrence of Solicited Systemic Symptoms

  Number of solicited symptoms

  20 day post primary infection for cohorts 1 and 2 and 20 days post reinfection, all cohorts

• 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)

  20 day post primary infection, cohorts 1 and 2 and 20 days post reinfection, all cohorts

• Duration of Solicited Systemic Symptoms

  Number of days per symptom

  20 day post primary infection, cohorts 1 and 2 and 20 days post reinfection, all cohorts

• Occurrence of Unsolicited Systemic Symptoms

  Number of unsolicited symptom

  28 day post primary infection, cohorts 1 and 2 and 28 days post reinfection, all cohorts

• 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)

  28 day post primary infection, cohorts 1 and 2 and 28 days post reinfection, all cohorts

• Duration of Unsolicited Systemic Symptoms

  Number of days per symptom

  28 day post primary infection, cohorts 1 and 2 and 28 days post reinfection, all cohorts

• Number of Abnormal Laboratory Measurements

  Total number of all abnormal labs

  28 day post primary infection, cohorts 1 and 2 and 28 days post reinfection, all cohorts

• 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)

  28 day post primary infection, cohorts 1 and 2 and 28 days post reinfection, all cohorts

• Duration of Abnormal Laboratory Measurements

  Number of days of abnormal labs

  28 day post primary infection, cohorts 1 and 2 and 28 days post reinfection, all cohorts

• Number of Serious Adverse Events

  Total number

  6 months post primary infection, cohorts 1 and 2

• Number of Serious Adverse Events

  Total number

  3 months post reinfection, cohorts 1 and 2

• Number of Serious Adverse Events

  Total number

  6 months post reinfection, cohorts 3 and 4

Study Arms (4)

Cohort 1 Naive DENV1

EXPERIMENTAL

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 181.

Biological: Dengue virus 1 Live Virus Human Challenge (DENV-1-LVHC)

Cohort 2 Naive DENV3

EXPERIMENTAL

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 181.

Biological: Dengue virus 3 Live Virus Human Challenge (DENV-3-LVHC)

Cohort 3 Returning DENV1

EXPERIMENTAL

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.

Biological: Dengue virus 1 Live Virus Human Challenge (DENV-1-LVHC)

Cohort 4 Returning DENV3

EXPERIMENTAL

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.

Biological: Dengue virus 3 Live Virus Human Challenge (DENV-3-LVHC)

Interventions

Dengue virus 1 Live Virus Human Challenge (DENV-1-LVHC) BIOLOGICAL

Dengue subtype 1 Challenge Virus (DENV-1) strain 45AZ5

Cohort 1 Naive DENV1; Cohort 3 Returning DENV1

Dengue virus 3 Live Virus Human Challenge (DENV-3-LVHC) BIOLOGICAL

Dengue subtype 3 Challenge Virus (DENV-3) strain CH53489

Cohort 2 Naive DENV3; Cohort 4 Returning DENV3

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• State University of New York - Upstate Medical University: lead
• U.S. Army Medical Research and Development Command: collaborator
• Walter Reed Army Institute of Research (WRAIR): collaborator

Study Sites (1)

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

Syracuse, New York, 13210, United States

Location

Related Publications (2)

• 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.

  PMID: 32572470 RESULT

• 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.

  PMID: 36288280 RESULT

MeSH Terms

Conditions

Dengue; Flavivirus Infections; Virus Diseases

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Study Officials

• Stephen J Thomas, MD

  State University of New York - Upstate Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2023
• First Posted: August 1, 2023
• Study Start: October 30, 2023
• Primary Completion: August 26, 2024
• Study Completion: August 26, 2024
• Last Updated: November 13, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)