Study of Varying Injection Schedules of TDENV-PIV Vaccine With AS03B Adjuvant and Placebo in Healthy US Adults

Dengue Clinical Trial

Official title:

A Phase 1/2, Randomized, Observer-blind Study of Varying Injection Schedules of a Tetravalent Dengue Virus Purified Inactivated Vaccine (TDENV-PIV) With AS03B Adjuvant and Placebo in Healthy Adults in the US

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02421367
• Other study ID #: S-14-13
• Secondary ID: WRAIR # 21952016
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 2015
• Est. completion date: March 2018

Study information

• Verified date: September 2019
• Source: U.S. Army Medical Research and Development Command
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is being conducted to evaluate the safety and immunogenicity and antibody persistence of the candidate dengue vaccine.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: March 2018
• Est. primary completion date: December 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 49 Years

Eligibility

Inclusion Criteria:

1. Subjects must be able to provide written informed consent.

2. Subjects must be healthy as established by medical history and clinical examination at study entry

3. Subjects who the investigator believes can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits, etc.)

4. Subjects at WRAIR CTC must be able to pass Department of Defense (DoD) base entry requirements, including the possession of a valid government issued ID card.

5. Male or non-pregnant, non-breastfeeding female between 20 and 49 years of age (inclusive) at the time of consent

6. Female subjects 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 ovariectomy, or is post-menopausal).

7. Female subjects of childbearing potential may be enrolled in the study, if all of the following apply:

• Practiced adequate contraception (see Definition of Terms, section 5) for 30 days prior to vaccination

• Has a negative urine pregnancy test on the day of vaccination

• Agrees to continue adequate contraception until two months after completion of the vaccination series.

Exclusion Criteria:

1. Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines/placebo during the period starting 30 days preceding the first dose of study vaccine/placebo and/or planned use during the study period

2. Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 90 days prior to the first vaccine/placebo dose (for corticosteroids, this will mean prednisone >=5mg/day or equivalent; inhaled, intranasal and topical steroids are allowed)

3. Planned administration or administration of a vaccine/product not planned in the study protocol during the period starting 30 days prior to the first dose of vaccine/placebo until 30 days after the last dose of study vaccine/placebo (routine influenza vaccination will be allowed as long as it is not administered within 14 days of the vaccine/placebo, and will not lead to study exclusion although it should be reported to the PI)

4. History of dengue infection or dengue illness, or history of flavivirus vaccination (e.g., yellow fever, tick-borne-encephalitis virus [TBEV], Japanese encephalitis, and dengue)

5. Planned administration of any flavivirus vaccine for the entire study duration

6. Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device)

7. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required)

8. Family history of congenital or hereditary immunodeficiency

9. Autoimmune disease or history of autoimmune disease

10. History of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccine/placebo or related to a study procedure

11. Major congenital defects or serious chronic illness

12. History of any neurological disorders or seizures

13. Diagnosed with excessive daytime sleepiness (unintended sleep episodes during the day present almost daily for at least 1 month) or narcolepsy; or history of narcolepsy in a subject's parent, sibling, or child

14. Acute disease and/or fever (=37.5°C/99.5°F oral body temperature) at the time of enrollment: note that a subject with a minor illness such as mild diarrhea, mild upper respiratory infection, etc., without fever, may be enrolled at the discretion of the investigator

15. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests

16. Administration of immunoglobulins and/or any blood products during the period starting 90 days preceding the first dose of study vaccine/placebo or planned administration during the study period

17. Recent history of chronic alcohol consumption (more than 2 drinks per day and/or drug abuse (based on subject reported history)

18. Pregnant or breastfeeding female or female currently planning to become pregnant or planning to discontinue adequate contraception

19. A planned move to a location that will prohibit participating in the trial until Study End for the participant

20. Any other condition which, in the opinion of the investigator, prevents the subject from participating in the study.

21. Subject seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), or human immunodeficiency virus antibodies (anti-HIV)

22. Safety laboratory test results at screening that are deemed clinically significant or more than Grade 1 deviation from normal

Related Conditions & MeSH terms

• Dengue

Intervention

Biological:
• TDENV-PIV with AS03B adjuvant. Placebo: 0.9% Sodium Chloride Solution.
Tetravalent dengue virus purified inactivated vaccine (1 µg/virus type)

Locations

Country	Name	City	State
United States	University of Maryland, Center for Vaccine Development,	Baltimore	Maryland
United States	WRAIR, Clinical Trials Center	Silver Spring	Maryland

Sponsors (3)

Lead Sponsor	Collaborator
U.S. Army Medical Research and Development Command	GlaxoSmithKline, Walter Reed Army Institute of Research (WRAIR)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of solicited local adverse events related to product		7-day follow-up period after each dose
Primary	Intensity of solicited local adverse events related to product		7-day follow-up period after each dose
Primary	Number of unsolicited adverse events related to product		28-day follow-up period after each dose
Primary	Intensity of unsolicited adverse events related to product		28-day follow-up period after each dose
Primary	Number of Grade 2 laboratory abnormalities		7-day follow-up period after each dose
Primary	Number of Grade 3 laboratory abnormalities		7-day follow-up period after each dose
Primary	Number of serious adverse events from day 0 through 28 days after the last dose		7 months after first dose
Primary	Number of potential immune-mediated diseases from Day 0 through 28 days after the last dose		7 months after first dose
Primary	Neutralizing antibody titers to each DENV type		Day 0 and 28 days after the second and third doses of TDENV-PIV
Primary	Number of general adverse events related to product		7-day follow-up period after each dose
Primary	Intensity of solicited general adverse events related to product		7-day follow-up period after each dose
Primary	Number of medically attended AEs related to product		Day 0 through 28 days after the last dose
Secondary	Number of potential immune-mediated diseases from post Month 7 to Study End		7 months after first dose to the end of study
Secondary	Number of serious adverse events related to product		7 months after first dose to the end of study
Secondary	Neutralizing antibody titers to each DENV type		56 days after the second dose of active vaccine
Secondary	Seropositivity status for each DENV type		28 days after the second dose of active vaccine for all groups
Secondary	Number of medically attended AEs from post Month 7 to Study End		7 months after first dose to the end of study
Secondary	Neutralizing antibody titers to each DENV type for the TDENV-PIV (0-1-6) group		56 days after the third dose of active vaccine
Secondary	Neutralizing antibody titers to each DENV type		4 months after the last dose of active vaccine
Secondary	Neutralizing antibody titers to each DENV type		6 months after the last dose of active vaccine
Secondary	Neutralizing antibody titers to each DENV type		9 months after the last dose of active vaccine
Secondary	Neutralizing antibody titers to each DENV type		12 months after the last dose of active vaccine
Secondary	Seropositivity status for each DENV type for the TDENV-PIV (0-1-6) group		28 days after the third dose of active vaccine
Secondary	Seropositivity status for each DENV type for the TDENV-PIV (0-1-6) group		56 days after the third dose of active vaccine
Secondary	Seropositivity status for each DENV type		4 months after the last dose of active vaccine for all groups
Secondary	Seropositivity status for each DENV type		6 months after the last dose of active vaccine for all groups
Secondary	Seropositivity status for each DENV type		9 months after the last dose of active vaccine for all groups
Secondary	Seropositivity status for each DENV type		12 months after the last dose of active vaccine for all groups