Comparison of Tetravalent Dengue Virus Purified Inactivated Vaccine and Tetravalent Dengue Virus Live Attenuated Vaccine

Study Overview
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Brief Summary
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This study is a Phase 1, randomized, open-label study of the prime-boost vaccine candidates given in the prime-boost regimen previously demonstrated to have a high level of immunogenicity and immune durability: Day 0 prime (PIV) and Day 180 boost (LAV), and compare it with a previously untested schedule: Day 0 prime (PIV) and Day 90 boost (LAV) in order to define the potential tradeoff between potential immunogenicity, including cell-mediated immunity, and a more practical dosing schedule.

Detailed Description
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This study is a Phase 1, randomized, open-label, study with 2 treatment groups (N=40): Group 1 (n=20): TDENV-PIV 4 µg + Alum adjuvant (Day 0), TDENV-LAV F17 (Day 180) Group 2 (n=20): TDENV-PIV 4 µg + Alum adjuvant (Day 0), TDENV-LAV F17 (Day 90) Investigational Product Dosage, Schedule, and Mode of Administration: TDENV-PIV Dosage: 0.5 mL of DENV serotypes 1-4 (4 µg / serotype) in alum adjuvant Mode of administration: intramuscular (IM) into the subject's upper arm, deltoid area of the subject's arm; vaccination will be given in the non-dominant arm whenever possible TDENV-LAV F17 Dosage: 0.5 mL of the post-transfection LAV F17 vaccine Mode of administration: subcutaneously into the upper-outer triceps/deltoid area of the subject's arm; vaccination will be given in the non-dominant arm whenever possible Schedule Varied, 2 vaccinations per volunteer in a heterologous prime-boost strategy. First dose on Day 0 (PIV) AND a second dose (LAV) on Day 180 for group 1. First dose on Day 0 (PIV) AND a second dose (LAV) on Day 90 for group 2. This study is intended to further evaluate the safety and reactogenicity of 2 tetravalent dengue vaccine (TDENV) candidates administered in a heterologous prime boost fashion with PIV followed by LAV 180 days later and to evaluate the safety and reactogenicity of a previously untested vaccination schedule consisting of PIV followed by LAV 90 days later.

Official Title
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A Phase 1, Randomized, Open-label, Comparison of Heterologous Prime-Boost Vaccination Schedules of Tetravalent Dengue Virus Purified Inactivated Vaccine (PIV) and Tetravalent Dengue Virus Live Attenuated Vaccine (LAV) in Healthy Adults

Conditions
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Dengue Virus

Intervention / Treatment
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* Biological: TDENV-PIV
* Biological: TDENV-LAV F17


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between 18 and 42 years of age (inclusive) at the time of consent Able to provide written informed consent Healthy as established by medical history and clinical examination and basic hematologic laboratory analysis before entering into the study Able and willing to comply with the requirements of the protocol (eg, document events in memory aid, return for follow-up visits, etc.) Dengue exposure naïve as established by pre-enrollment dengue PRNT testing and questioning of volunteer Female subject of non-childbearing potential (non-childbearing potential is defined as having either a current bilateral tubal ligation at least 3 months prior to enrollment or a history of an hysterectomy, bilateral oophorectomy, or is post-menopause(12 months or more since last menstrual period)) or Female subject of childbearing potential may be enrolled in the study, if the subject has: Practiced adequate contraception for 30 days prior to vaccinations, and A negative urine pregnancy test on each day of vaccination, and Agreed to continue adequate contraception through at least 3 months following last vaccination Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine or device) other than the study vaccines during the period starting 30 days preceding the first dose of study vaccine and/or planned use during the study period Chronic administration (defined as more than 14 days in total) of prescription immunosuppressants or other prescription immune-modifying drugs during the period starting 180 days prior to the first vaccine dose For corticosteroids, this will mean prednisone ≥ 20 mg/d or equivalent Inhaled and topical steroids are allowed History of or active use of cancer chemotherapy or radiation therapy for the treatment of cancer Receipt or planned receipt of a vaccine/product outside the study protocol within 30 days of each scheduled dose of an investigational product Planned administration of any flavivirus vaccine, to include licensed vaccines for Yellow Fever or Japanese Encephalitis Virus as well as other investigational vaccines for dengue, Zika, West Nile, other flavivirus, for the entire study duration Previous receipt of a foreign or investigational dengue vaccine 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) Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination History of, or current, auto-immune disease History of any reaction or hypersensitivity likely to be triggered by any component of the vaccines or related to a study procedure (This includes hypersensitivity reactions to alum, streptomycin, neomycin, or any other flavivirus vaccine, such as Yellow Fever virus and Japanese Encephalitis virus vaccines) Major congenital defects or serious chronic illness History of any chronic neurological disorders or chronic and/or uncontrolled seizures Acute infectious disease and/or fever (oral body temperature ≥ 100.4°F/38.0°C) at the time of enrollment (a subject with a minor illness, ie, mild diarrhea, mild upper respiratory infection, etc., without fever, may be enrolled at the discretion of the investigator) Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by history, physical examination or laboratory screening tests Receipt of immunoglobulins or any blood products during the period starting 90 days preceding the first dose of study vaccine or planned receipt during the study period Donated blood within 8 weeks before first scheduled investigational vaccine receipt or planned donation of blood products throughout the study period History of chronic alcohol abuse and/or drug abuse that, in the opinion of the investigator, could result in poor compliance with study requirements. Pregnant or breastfeeding female or female planning to become pregnant or planning to discontinue contraceptive precautions A planned move to a location that will prohibit compliance with the requirements of the trial Subject seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), or human immunodeficiency virus antibodies (anti-HIV) Safety laboratory test results that are outside the acceptable values at screening: > 110% upper limit of normal (ULN) for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, creatinine, serum urea nitrogen (SUN) and bilirubin (total and direct) < 100% lower limit of normal (LLN) or > 120% ULN for hemoglobin, hematocrit and platelet count < 75% LLN or >110% ULN for total white blood cell count (WBC) Note: Per guidance in section 8.1, abnormal lab(s) may be repeated x1 in the screening window provided the total amount of blood drawn for all screening labs does not exceed 50 mL. Active Diabetes or active peptic ulcer disease (PUD) 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 meeting all requirements of the study Chronic migraine headaches, defined as more than 15 headache days per month over a 3 month period of which more than 8 are migrainous, in the absence of medication over use Chronic medical condition that, in the opinion of the investigator, impacts subject safety Any other condition which, in the opinion of the investigator, prevents the subject from meeting all requirements of the study. Do not wish to have their blood stored and used for future research

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 42 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: TDENV-PIV on Day 0<br>Dosage: 0.5 mL of DENV serotypes 1-4 (4 µg / serotype) in alum adjuvant Mode of administration: intramuscular (IM) into the subject's upper arm, deltoid area of the subject's arm; vaccination will be given in the non-dominant arm whenever possible | Biological: TDENV-PIV<br>* Dosage: 0.5 mL of DENV serotypes 1-4 (4 µg / serotype) in alum adjuvant Mode of administration: intramuscular (IM) into the subject's upper arm, deltoid area of the subject's arm; vaccination will be given in the non-dominant arm whenever possible<br>|
| Experimental: Group 1: TDENV-LAV F17 on Day 180<br>Dosage: 0.5 mL of the post-transfection LAV F17 vaccine Mode of administration: subcutaneously into the upper-outer triceps/deltoid area of the subject's arm; vaccination will be given in the non-dominant arm whenever possible | Biological: TDENV-LAV F17<br>* Dosage: 0.5 mL of the post-transfection LAV F17 vaccine Mode of administration: subcutaneously into the upper-outer triceps/deltoid area of the subject's arm; vaccination will be given in the non-dominant arm whenever possible.<br>|
| Experimental: Group 2: TDENV-PIV on Day 0<br>Dosage: 0.5 mL of DENV serotypes 1-4 (4 µg / serotype) in alum adjuvant Mode of administration: intramuscular (IM) into the subject's upper arm, deltoid area of the subject's arm; vaccination will be given in the non-dominant arm whenever possible | Biological: TDENV-PIV<br>* Dosage: 0.5 mL of DENV serotypes 1-4 (4 µg / serotype) in alum adjuvant Mode of administration: intramuscular (IM) into the subject's upper arm, deltoid area of the subject's arm; vaccination will be given in the non-dominant arm whenever possible<br>|
| Experimental: Group 2:TDENV-LAV F17 on Day 90<br>Dosage: 0.5 mL of the post-transfection LAV F17 vaccine Mode of administration: subcutaneously into the upper-outer triceps/deltoid area of the subject's arm; vaccination will be given in the non-dominant arm whenever possible | Biological: TDENV-LAV F17<br>* Dosage: 0.5 mL of the post-transfection LAV F17 vaccine Mode of administration: subcutaneously into the upper-outer triceps/deltoid area of the subject's arm; vaccination will be given in the non-dominant arm whenever possible.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With At Least One Local Solicited Adverse Events (AE) during the 28 Day Follow-up After Prime and Boost Vaccinations | The number of subjects with at least one local solicited adverse event (AE), at least one general solicited AE and any solicited AE during the 28-day follow-up period for prime and boost vaccination will be tabulated with 95% confidence interval (CI) after each vaccine dose and overall. | 28 day follow-up period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects reporting at least one of each type of unsolicited AE during the 28-day follow-up period after each vaccination | The number of subjects reporting at least one of each type of unsolicited AE during the 28-day follow-up period after each vaccination will be tabulated with 95% CIs | 28 day follow-up period |