ADVP005; Dengue CVD 12000 - Dengue-1-Virus Live Virus Human Challenge (DENV-1-LVHC)

• ClinicalTrials.gov Identifier: NCT04786457
• Recruitment Status: Completed
• First Posted: March 8, 2021
• Last Update Posted: October 28, 2021
• Sponsor: University of Maryland, Baltimore
• Collaborators: United States Army Medical Materiel Development Activity; Medical Technology Enterprise Consortium (MTEC)
• Information provided by (Responsible Party): Kirsten Lyke, University of Maryland, Baltimore

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Dengue	Biological: Dengue 1 Live Virus Human Challenge (DENV-1-LVHC)	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: 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)
• Actual Study Start Date: November 30, 2020
• Actual Primary Completion Date: July 9, 2021
• Actual Study Completion Date: July 9, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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	Biological: Dengue 1 Live Virus Human Challenge (DENV-1-LVHC); one subcutaneous injection of Dengue 1 Live Virus Human Challenge (DENV-1-LVHC) at 0.5 mL of 6.5 x 10^3 PFU/mL

Outcome Measures

Primary Outcome Measures :

1. Solicited Injection Site Adverse Events [ Time Frame: approximately six months ]
   solicited injection site adverse event until 7 days post virus inoculation
2. Unsolicited Injection Site Adverse Events [ Time Frame: approximately six months ]
   unsolicited injection site adverse events until 28 days post virus inoculation or 7 days post hospitalization, whichever is later
3. Solicited Systemic Adverse Events [ Time Frame: approximately six months ]
   solicited systemic adverse events until 28 days post virus inoculation or 7 days post hospitalization, whichever is later
4. Incidence of Abnormal Laboratory Measurements [ Time Frame: approximately six months ]
   Incidence of abnormal laboratory measurements until 28 days post virus inoculation or 7 days post hospitalization, whichever is later
5. Dengue-Related Adverse Events [ Time Frame: approximately six months ]
   dengue-related like adverse events until 28 days post virus inoculation or 7 days post inpatient whichever is later
6. Unsolicited Systemic Adverse Events [ Time Frame: approximately six months ]
   unsolicited systemic adverse events until 28 days post virus inoculation or 7 days post hospitalization, whichever is later
7. Short-Term SAEs [ Time Frame: approximately six months ]
   Number of SAEs until 28 days post virus inoculation or 7 days post hospitalization, whichever is later
8. Long-Term SAEs [ Time Frame: approximately seven months ]
   Number of SAEs until 6 months post virus inoculation
9. Fever [ Time Frame: approximately seven months ]
   The occurrence of fever defined as greater than or equal to 38°C (100.4° F) measured at least 2 times at least 4 hours apart

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• 1. Male or non-pregnant, non-breastfeeding female between 18 and 50 years of age (inclusive) at the time of consent.
• 2. Tetravalent dengue antibody response at 28 days following final vaccination for vaccinated groups of volunteers.
• 3. Volunteers must be able and willing to provide written informed consent.
• 4. Volunteers must be healthy as established by medical history and clinical examination at study entry.
• 5. Volunteers must pass a comprehension test and be able to comply with all study requirements.
• 6. 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).
• 7. 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
• 8. Provide consent for release of medical history records from primary care physician, college or university medical center, urgent care, or emergency room visit

Exclusion Criteria:

• 1. Planned travel during the study period (180 days) which would interfere with the ability to complete all study visits
• 2. 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
• 3. Volunteer seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), or human immunodeficiency virus antibodies (anti-HIV)
• 4. Unvaccinated volunteers positive for antibodies to flaviviruses (FV) to include dengue virus, West Nile virus, Yellow Fever virus, Zika virus, and Japanese encephalitis virus.
• 5. 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)
• 6. Medical history of, or current, diabetes, chronic obstructive pulmonary disease, peptic ulcer disease, coronary artery disease, cardiac arrhythmia, cardiomyopathy, pericarditis, or auto-immune disease
• 7. 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)
• 8. History of Guillain-Barré syndrome (GBS)
• 9. 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
• 10. 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
• 11. Significant screening physical examination abnormalities at the discretion of the investigator, including a BMI > 35 kg/m2
• 12. Women who intend to become pregnant or men who intend to father a child during the study period (approximately 6 months)
• 13. Female: pregnant, lactating or history of heavy menstrual bleeding menstrual periods lasting consistently and regularly longer than 6 days, or consistently and regularly requiring 5 or more pads or tampons per day, and volunteer to the opinion and review of the investigator.
• 14. Female volunteers using an intrauterine device (IUD) or Mirena®
• 15. Female volunteers with a history of clinically significant fibroids or uterine polyps, endometriosis, dysmenorrhea, adenomyosis, and uterine scarring (e.g. after D&C), unless treated, with no active clinically significant disease
• 16. Allergy (hives, shortness of breath, swelling of the lips or throat), or hospitalization related to a previous vaccination, anaphylaxis of unknown etiology, or 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
• 17. Recent blood donation within prior 56 days of inoculation or planning to donate blood in the one 1 year following inoculation with dengue virus
• 18. Receipt of blood products or antibodies within 90 days of inoculation or during the study period
• 19. Any personal beliefs that bar the administration of blood products, transfusions, or serum albumin
• 20. Participation in the 4 weeks preceding inoculation, or planned participation during the present trial period, in another clinical trial investigating a vaccine except for participation in the ADVP003 or ADVP004 study, drug, medical device, or medical procedure
• 21. Planned administration of a licensed or study vaccine not planned in the study protocol during the period starting 30 days prior to the DHIM for a live vaccine or 14 days prior to DHIM for inactivated vaccines and extending until 56 days after study completion
• 22. Planned or current administration of an HMG-CoA reductase inhibitor (i.e., lovastatin, simvastatin, atorvastatin, etc.)
• 23. Currently taking methadone or suboxone
• 24. Currently regularly taking anti-coagulant medication, aspirin or non-steroidal anti-inflammatory drugs (NSAIDs)
• 25. 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
• 26. Chronic or recent acute medical condition that, in the opinion of the investigator, impacts volunteer safety.

Contacts and Locations

Locations

United States, Maryland

University of Maryland, Baltimore, Center for Vaccine Development and Global Health

Baltimore, Maryland, United States, 21201

Sponsors and Collaborators

University of Maryland, Baltimore

United States Army Medical Materiel Development Activity

Medical Technology Enterprise Consortium (MTEC)

More Information

• Responsible Party: Kirsten Lyke, Professor of Medicine, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT04786457
• Other Study ID Numbers: HP-00088798
• First Posted: March 8, 2021
• Last Update Posted: October 28, 2021
• Last Verified: October 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Dengue; Arbovirus Infections; Vector Borne Diseases; Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral