A Phase 1, Open-Label Clinical Trial With Dengue-1-Virus Live Virus Human Challenge (DENV-1-LVHC) Assessment of Healthy U.S. Adults Previously Primed With Tetravalent Dengue Virus Purified Inactivated Vaccine (TDEN-PIV) and Boosted With Tetravalent Dengue Virus Live Attenuated Vaccine Formulation (TDEN LAV)
Overview
- Phase
- Phase 1
- Intervention
- Dengue 1 Live Virus Human Challenge (DENV-1-LVHC)
- Conditions
- Dengue
- Sponsor
- University of Maryland, Baltimore
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Number of Participants With Solicited Injection Site Adverse Events
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The purpose of this research study is to test the protection of volunteers previously vaccinated with Tetravalent Dengue Virus (TDEN) Purified Inactivated Vaccine (PIV) with alum and boosted with TDEN live attenuated vaccine (LAV) formulation against a weakened form of an experimental dengue virus challenge. The Investigators will also include people that have not received the study vaccine. The Investigators are collecting information about how the vaccine protects against a dengue virus challenge as well as adding to knowledge about the safety of the challenge.
Detailed Description
The purpose of this research study is to test the protection of volunteers previously vaccinated with Tetravalent Dengue Virus (TDEN) Purified Inactivated Vaccine (PIV) with alum and boosted with TDEN live attenuated vaccine (LAV) formulation against a weakened form of an experimental dengue virus challenge. The Investigators will also include people that have not received the study vaccine. The Investigators are collecting information about how the vaccine protects against a dengue virus challenge as well as adding to knowledge about the safety of the challenge. The information will help Investigators develop vaccines to protect people from dengue. Participation is voluntary. The duration of participation will last for 180 days (six months). After participants are exposed to the weakened dengue virus, the Investigators will follow them closely to measure their symptoms. Like the flu, participants might expect to have a headache, rash, body aches, fever and chills or they may experience no symptoms whatsoever. If a participant does develops symptoms, the Investigators will monitor him/her closely in a local hotel or a wing of our hospital to ensure safety and to treat symptoms if they occur. Participants will be compensated for their time.
Investigators
Kirsten Lyke
Professor of Medicine
University of Maryland, Baltimore
Eligibility Criteria
Inclusion Criteria
- •Male or non-pregnant, non-breastfeeding female between 18 and 50 years of age (inclusive) at the time of consent.
- •Tetravalent dengue antibody response at 28 days following final vaccination for vaccinated groups of volunteers.
- •Volunteers must be able and willing to provide written informed consent.
- •Volunteers must be healthy as established by medical history and clinical examination at study entry.
- •Volunteers must pass a comprehension test and be able to comply with all study requirements.
- •Female volunteers of non-childbearing potential (non-childbearing potential is defined as having had one of the following: a tubal ligation at least 3 months prior to enrollment, a hysterectomy, an oophorectomy, or is post-menopausal).
- •Female volunteers of childbearing potential may be enrolled in the study, if all of the following apply:
- •Practiced adequate contraception (see Definition of Terms, section 5.4.2.3.) for 30 days prior to challenge
- •Has a negative urine pregnancy test on the day of DHIM
- •Agrees to continue adequate contraception until two months after completion of the DHIM
Exclusion Criteria
- •Planned travel during the study period (180 days) which would interfere with the ability to complete all study visits
- •Recent (in the past 4 weeks) travel to any dengue endemic area. These potential volunteers may be eligible for enrollment a minimum of 4 weeks later
- •Volunteer seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), or human immunodeficiency virus antibodies (anti-HIV)
- •Unvaccinated volunteers positive for antibodies to flaviviruses (FV) to include dengue virus, West Nile virus, Yellow Fever virus, Zika virus, and Japanese encephalitis virus.
- •Any history of FV infection or FV vaccination except for participation in the ADVP003 or ADVP004 dengue vaccination studies; during the study period (Note: Late time point serology from the trials can be tested concomitant to screening serology to clarify if incident FV infection has occurred between vaccination and challenge)
- •Medical history of, or current, diabetes, chronic obstructive pulmonary disease, peptic ulcer disease, coronary artery disease, cardiac arrhythmia, cardiomyopathy, pericarditis, or auto-immune disease
- •Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
- •History of Guillain-Barré syndrome (GBS)
- •History of bipolar disorder, 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 volunteer from participating in the study
- •Safety laboratory test results at screening that are deemed clinically significant or more than Grade 1 deviation from normal with the exception of PT/PTT, fibrinogen decrease, ALT/AST increase (\<1.1 x ULN acceptable), platelet decrease which will be exclusionary at Grade 1 or higher
Arms & Interventions
Dengue 1 Live Virus Human Challenge (DENV-1-LVHC)
open-label injection of DENV-1-LVHC to 15-20 adults who were previously vaccinated and 5 adults who have never received a dengue vaccination
Intervention: Dengue 1 Live Virus Human Challenge (DENV-1-LVHC)
Outcomes
Primary Outcomes
Number of Participants With Solicited Injection Site Adverse Events
Time Frame: Days 2, 4, 5, 6, and 7
Number of Participants with Solicited Injection Site Erythema - solicited injection site adverse event until 7 days post virus inoculation
Number of Participants With Unsolicited Injection Site Adverse Events
Time Frame: Days 2, 4, 5-16, 28 (until 28 days post virus inoculation or 7 days post hospitalization, whichever is later, up to a maximum of 28 days)
Number of Participants with Injection site pain - unsolicited injection site adverse events until 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Number of Participants With Solicited Systemic Adverse Events
Time Frame: Days 2, 4-16, 19, 22, 25, and 28 (until 28 days post virus inoculation or 7 days post hospitalization, whichever is later, up to a maximum of 28 days)
Number of participants with solicited systemic adverse events until 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Number of Participants With Incidence of Abnormal Laboratory Measurements
Time Frame: Days 2, 4-16, 19, 22, 25, and 28 (until 28 days post virus inoculation or 7 days post hospitalization, whichever is later, up to a maximum of 28 days)
Number of participants with incidence of abnormal laboratory measurements until 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Dengue-Related Illness Index
Time Frame: Days 1-16
Scales: Clinical Symptoms: None=0, Mild=1, Moderate=2, Severe=3 (Min Score=0, Max=3) Laboratory Abnormalities: None=0, Mild=1, Moderate=2, Severe=3 based on modified FDA CBER laboratory scale (per protocol) (Min=0, Max=3) Symptoms (Clinical symptoms or Laboratory Abnormalities) duration: 1 point/day (Day 1-16) (Min=0, Max=16) Subscale A (Symptom Duration): 1 point/day (Day 1-16) across 10 Clinical/Laboratory findings (Min = 0, Max = 160) Subscale B (Symptom # per day): 1 point/ Clinical/Laboratory finding (n=10) per day across 16 days Min=0, Max=160 Subscale C (Max Severity Score/day): None=0, Mild=1, Moderate=2, Severe=3 across 16 days: Min=0, Max=48 Total Range in DII score (total scale) which equates to subscale (A + B + C)/3: Min=0, Max=122.7 https://doi.org/10.1016/s1473-3099(24)00100-2.
Number of Participants With Unsolicited Systemic Adverse Events
Time Frame: Days 2, 4-16, 19, 22, 25, and 28 (until 28 days post virus inoculation or 7 days post hospitalization, whichever is later, up to a maximum of 28 days)
Number of participants with unsolicited systemic adverse events until 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Number of Participants With Short-Term SAEs
Time Frame: Days 2, 4-16, 19, 22, 25, and 28 (until 28 days post virus inoculation or 7 days post hospitalization, whichever is later, up to a maximum of 28 days)
Number of participants with SAEs until 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Number of Participants With Long-Term SAEs
Time Frame: Days 2-180
Number of participants with SAEs until 6 months post virus inoculation
Number of Participants With Persistent Fever
Time Frame: Days 2-28
Number of participants with persistent fever defined as greater than or equal to 38°C (100.4° F) measured at least 2 times at least 4 hours apart