Title

A Study of Two Doses of WRAIR Dengue Vaccine Administered Six Months Apart to Healthy Adults and Children
Phase II, Randomized, Double-blind, Placebo-controlled Study of Two Doses of WRAIR Live Attenuated Tetravalent Dengue Vaccine Formulations, Administered Six Months Apart, to Healthy Adults and Children
  • Phase

    Phase 2
  • Study Type

    Interventional
  • Intervention/Treatment

    tdenv-f17 t-den- f19 ...
  • Study Participants

    636
The purpose of this study is to evaluate the safety and effectiveness of two different formulations of an investigational dengue vaccine (T-DEN) against a placebo vaccine when two doses are given six months apart to adults and children.
In this study, children and adults at multiple sites in Puerto Rico will be randomly allocated to receive one of two T-DEN formulations or placebo. Subjects will be stratified by age group (a specific number of subjects in each of 4 age groups [12 months to 50 years of age] will be enrolled). The study includes 6 scheduled visits and 4 scheduled venipunctures. Safety follow-up for dengue may require unscheduled visits and venipunctures.> Multiple DEN virus serotypes are endemic in Puerto Rico and all residents are considered to be at risk for dengue. The results of this phase II study will provide a basis for identifying the vaccine formulations which elicit neutralizing antibodies to all four dengue virus serotypes in a high proportion of vaccine recipients. The most immunogenic and well tolerated candidate formulation identified in this study will be considered for advancement to phase III development.>
Study Started
Jul 31
2007
Primary Completion
Apr 30
2010
Study Completion
Apr 30
2010
Results Posted
Jun 06
2017
Last Update
Jul 02
2017

Other Placebo

Lyophilized, single dose vials and sterile water for > injection; 0.5 mL dose; Vaccination schedule: 0, 6 months

Biological T-DEN-Post-Transfection F17

Lyophilized, single dose vials and sterile water for injection; 0.5 mL dose at 0 and 6 months

Biological T-DEN-Post-Transfection F19

Lyophilized, single dose vials and sterile water for injection; 0.5 mL dose at 0 and 6 months

T-DEN-Post-Transfection F17 Experimental

Post-Transfection F17, full dose

T-DEN-Post-Transfection F19 Experimental

Post-Transfection F19, full dose

Placebo Placebo Comparator

Control

Criteria

Inclusion Criteria:>

Subjects who the investigator believes that they and/or their parents/guardians can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits) should be enrolled in the study.>
A healthy male or non-pregnant female between 12 months (mths) and 50 years (yrs) of age at the time of the first vaccination;>
Free of obvious health problems as established by medical history and physical examination before entering into the study;>
For children: 23mths of age, full compliance with the United States Advisory Committee on Immunization Practices (U.S. ACIP) recommended childhood immunization schedule;>
Written informed consent obtained from the subject or a parent/guardian and assent for subjects 7-20 yrs of age;>
If the subject is female, she must be of non-childbearing potential, i.e. either pre-menarcheal, surgically sterilized or one year post-menopausal; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions (i.e. intrauterine contraceptive device; condom and spermicide combination, oral contraceptives or other equivalent hormonal contraception, e.g. progestin implantable, cutaneous hormonal patch or injectable contraceptives) for 30 days (dys) prior to vaccination, have a negative pregnancy test within 48 hrs prior to vaccination and must agree to continue such precautions for 60 dys after completion of the vaccination series. Any child who begins menarche during the study period must follow the same precautions listed above, from menarche until 60 dys after the second vaccine dose.>

Exclusion Criteria:>

Pregnant or lactating female;>
Female planning to become pregnant or planning to discontinue abstinence or contraceptive precautions;>
History of any neurological or behavioral disorder or seizures, with the exception of a single febrile seizure in childhood; >
History of allergic disease/reaction likely to be exacerbated by any component of the vaccine;>
Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, renal, hematologic or endocrine functional defect, as determined by physical examination or laboratory tests;>
Any confirmed or suspected immunosuppressive or immunodeficient condition;>
Acute disease at the time of enrollment (acute disease is defined as the presence of a moderate or severe illness with or without fever); note that vaccine can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e., equivalent to an oral temperature <37.5°C/<99.5°F.>
Chronic hepatomegaly, right upper quadrant abdominal pain or tenderness;>
Chronic splenomegaly, left upper quadrant abdominal pain or tenderness;>
Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 dys preceding the first dose of study vaccine/placebo or planned use during the study period;>
Planned administration of a vaccine not foreseen by the study protocol during the period starting from 30 dys before each dose of the study vaccine and ending 30 dys after; with the exception of standard infant and children "inactivated" vaccines or the inactivated influenza vaccine administered to adults or children; >
A planned move to a location that will prohibit participating in the trial for the 12 mth duration;>
Chronic administration (defined as more than 14 dys) of immunosuppressants or other immune-modifying drugs within 90 dys preceding the first dose or planned administration during the study period. For corticosteroids, this will mean prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed;>
Administration of immunoglobulins and/or blood products within 90 dys preceding the first dose or planned administration during the study period;>
Hypertension;>
Chest pain, palpitations, dizziness, shortness of breath unrelated to asthma, arrhythmias or friction rubs;>
Any chronic systemic drug therapy to be continued during the study period (except for vitamin/mineral supplements, routine treatment for gastro-esophageal reflux);>
Potential adult volunteers, or parents of potential child volunteers, who do not have easy access to a fixed or mobile telephone;>
History of chronic alcohol consumption and/or drug abuse.

Summary

T-DEN-Post-Transfection F17

T-DEN-Post-Transfection F19

Placebo

All Events

Event Type Organ System Event Term T-DEN-Post-Transfection F17 T-DEN-Post-Transfection F19 Placebo

Safety: Incidence of All and Grade 3 Solicited Local Symptoms

Incidence of all and grade 3 (prevents normal, everyday activities) solicited local and general symptoms within the 21-day follow-up period (Total vaccinated cohort)

T-DEN-Post-Transfection F17

Abdominal Pain - All

28.0
number of occurances

Abdominal Pain - Grade 3

All Grade 3 AEs

114.0
number of occurances

Fatigue - All

28.0
number of occurances

Fatigue - Grade 3

Fever - All

103.0
number of occurances

Fever - Grade 3

10.0
number of occurances

Headache - All

75.0
number of occurances

Headache - Grade 3

3.0
number of occurances

Pain - All

55.0
number of occurances

Pain - Grade 3

1.0
number of occurances

Pruritus - All

25.0
number of occurances

Pruritus - Grade 3

Rash - All

18.0
number of occurances

Rash - Grade 3

Redness - All

31.0
number of occurances

Redness - Grade 3

6.0
number of occurances

Swelling - All

3.0
number of occurances

Swelling - Grade 3

3.0
number of occurances

Vomiting - All

24.0
number of occurances

Vomiting - Grade 3

T-DEN-Post-Transfection F19

Abdominal Pain - All

39.0
number of occurances

Abdominal Pain - Grade 3

1.0
number of occurances

All Grade 3 AEs

98.0
number of occurances

Fatigue - All

33.0
number of occurances

Fatigue - Grade 3

1.0
number of occurances

Fever - All

100.0
number of occurances

Fever - Grade 3

13.0
number of occurances

Headache - All

73.0
number of occurances

Headache - Grade 3

1.0
number of occurances

Pain - All

60.0
number of occurances

Pain - Grade 3

Pruritus - All

27.0
number of occurances

Pruritus - Grade 3

Rash - All

20.0
number of occurances

Rash - Grade 3

Redness - All

22.0
number of occurances

Redness - Grade 3

2.0
number of occurances

Swelling - All

14.0
number of occurances

Swelling - Grade 3

Vomiting - All

26.0
number of occurances

Vomiting - Grade 3

1.0
number of occurances

Placebo

Abdominal Pain - All

28.0
number of occurances

Abdominal Pain - Grade 3

1.0
number of occurances

All Grade 3 AEs

84.0
number of occurances

Fatigue - All

32.0
number of occurances

Fatigue - Grade 3

Fever - All

83.0
number of occurances

Fever - Grade 3

9.0
number of occurances

Headache - All

72.0
number of occurances

Headache - Grade 3

6.0
number of occurances

Pain - All

48.0
number of occurances

Pain - Grade 3

Pruritus - All

19.0
number of occurances

Pruritus - Grade 3

1.0
number of occurances

Rash - All

10.0
number of occurances

Rash - Grade 3

1.0
number of occurances

Redness - All

20.0
number of occurances

Redness - Grade 3

5.0
number of occurances

Swelling - All

10.0
number of occurances

Swelling - Grade 3

1.0
number of occurances

Vomiting - All

21.0
number of occurances

Vomiting - Grade 3

1.0
number of occurances

Safety: Summary of Unsolicited Adverse Events Within the 31-day Post-vaccination Period

Summary of unsolicited Adverse Events within the 31-day post-vaccination period by age group (total vaccinated cohort)

T-DEN-Post-Transfection F17

T-DEN-Post-Transfection F19

Placebo

Safety: Occurrence of Serious Adverse Events (SAEs)

Summary of SAEs, 6 months + 30 day follow-up period after last vaccine dose

T-DEN-Post-Transfection F17

T-DEN-Post-Transfection F19

Placebo

Incidence of Suspected and Laboratory Confirmed Dengue

Incidence of suspected and confirmed dengue reported during the 31-day (Days 0-30) post-vaccination period and after the 31-day period

During 31-Day Post Vaccination: F17

Dose 1: Confirmed dengue fever

Dose 1: Suspected dengue fever

3.0
dengue fever cases

Dose 1: Suspected with med. attention

3.0
dengue fever cases

Dose 2: Confirmed dengue fever

Dose 2: Suspected dengue fever

Dose 2: Suspected with med. attention

Overall Subject: Confirmed dengue fever

Overall Subject: Suspected dengue fever

3.0
dengue fever cases

Overall Subject: Suspected with med. attention

3.0
dengue fever cases

During 31-Day Post Vaccination: F19

Dose 1: Confirmed dengue fever

Dose 1: Suspected dengue fever

3.0
dengue fever cases

Dose 1: Suspected with med. attention

3.0
dengue fever cases

Dose 2: Confirmed dengue fever

Dose 2: Suspected dengue fever

1.0
dengue fever cases

Dose 2: Suspected with med. attention

1.0
dengue fever cases

Overall Subject: Confirmed dengue fever

Overall Subject: Suspected dengue fever

4.0
dengue fever cases

Overall Subject: Suspected with med. attention

4.0
dengue fever cases

During 31-Day Post Vaccination: Placebo

Dose 1: Confirmed dengue fever

Dose 1: Suspected dengue fever

Dose 1: Suspected with med. attention

Dose 2: Confirmed dengue fever

Dose 2: Suspected dengue fever

1.0
dengue fever cases

Dose 2: Suspected with med. attention

1.0
dengue fever cases

Overall Subject: Confirmed dengue fever

Overall Subject: Suspected dengue fever

1.0
dengue fever cases

Overall Subject: Suspected with med. attention

1.0
dengue fever cases

After 31-Day Post Vaccination Period: F17

Dose 1: Confirmed dengue fever

Dose 1: Suspected dengue fever

3.0
dengue fever cases

Dose 1: Suspected with med. attention

3.0
dengue fever cases

Dose 2: Confirmed dengue fever

Dose 2: Suspected dengue fever

1.0
dengue fever cases

Dose 2: Suspected with med. attention

1.0
dengue fever cases

Overall Subject: Confirmed dengue fever

Overall Subject: Suspected dengue fever

4.0
dengue fever cases

Overall Subject: Suspected with med. attention

4.0
dengue fever cases

After 31-Day Post Vaccination Period: F19

Dose 1: Confirmed dengue fever

Dose 1: Suspected dengue fever

3.0
dengue fever cases

Dose 1: Suspected with med. attention

3.0
dengue fever cases

Dose 2: Confirmed dengue fever

Dose 2: Suspected dengue fever

1.0
dengue fever cases

Dose 2: Suspected with med. attention

1.0
dengue fever cases

Overall Subject: Confirmed dengue fever

Overall Subject: Suspected dengue fever

4.0
dengue fever cases

Overall Subject: Suspected with med. attention

4.0
dengue fever cases

After 31-Day Post-Vaccination Period: Placebo

Dose 1: Confirmed dengue fever

Dose 1: Suspected dengue fever

3.0
dengue fever cases

Dose 1: Suspected with med. attention

3.0
dengue fever cases

Dose 2: Confirmed dengue fever

Dose 2: Suspected dengue fever

Dose 2: Suspected with med. attention

Overall Subject: Confirmed dengue fever

Overall Subject: Suspected dengue fever

3.0
dengue fever cases

Overall Subject: Suspected with med. attention

3.0
dengue fever cases

GMTs for Antibody Titer Above the Assay Cut Off to Each DEN Serotype for Unprimed and Primed Subjects

Comparison of F17 and F19 formulations in terms of GMTs at month 7 (one month post dose 2) for each DEN type, -unprimed and primed subjects

T-DEN-Post-Transfection F17

Primed Subjects: DEN-1

1412.8
titers (Mean)
95% Confidence Interval: 1191.5 to 1675.3

Primed Subjects: DEN-2

1514.4
titers (Mean)
95% Confidence Interval: 1322.2 to 1734.6

Primed Subjects: DEN-3

1130.0
titers (Mean)
95% Confidence Interval: 920.0 to 1388.0

Primed Subjects: DEN-4

1228.4
titers (Mean)
95% Confidence Interval: 1014.1 to 1488.0

Unprimed Subjects: DEN-1

130.9
titers (Mean)
95% Confidence Interval: 84.1 to 203.7

Unprimed Subjects: DEN-2

218.6
titers (Mean)
95% Confidence Interval: 125.3 to 381.3

Unprimed Subjects: DEN-3

124.5
titers (Mean)
95% Confidence Interval: 76.9 to 201.6

Unprimed Subjects: DEN-4

377.7
titers (Mean)
95% Confidence Interval: 249.4 to 572.0

T-DEN-Post-Transfection F19

Primed Subjects: DEN-1

1324.1
titers (Mean)
95% Confidence Interval: 1104.1 to 1587.9

Primed Subjects: DEN-2

1338.5
titers (Mean)
95% Confidence Interval: 1105.6 to 1620.6

Primed Subjects: DEN-3

901.4
titers (Mean)
95% Confidence Interval: 707.6 to 1148.3

Primed Subjects: DEN-4

1020.8
titers (Mean)
95% Confidence Interval: 809.5 to 1287.4

Unprimed Subjects: DEN-1

84.4
titers (Mean)
95% Confidence Interval: 43.6 to 163.5

Unprimed Subjects: DEN-2

215.2
titers (Mean)
95% Confidence Interval: 116.7 to 396.7

Unprimed Subjects: DEN-3

60.3
titers (Mean)
95% Confidence Interval: 33.0 to 110.2

Unprimed Subjects: DEN-4

105.9
titers (Mean)
95% Confidence Interval: 55.8 to 201.0

Percent of Subjects With Neut. Antibody Titer Above the Assay Cut-off to All Dengue Serotypes

Monovalent, bivalent, trivalent and tetravalent response for DEN neut. antibodies for unprimed and primed subjects

F17: Pre-vaccination

Primed: Valence=Bivalent

Primed: Valence=Monovalent

3.3
% of subjects
95% Confidence Interval: 0.7 to 9.3

Primed: Valence=None

Primed: Valence=Tetravalent

96.5
% of subjects
95% Confidence Interval: 89.1 to 98.8

Primed: Valence=Trivalent

1.1
% of subjects
95% Confidence Interval: 0.0 to 6.0

Unprimed: Valence=Bivalent

Unprimed: Valence=Monovalent

Unprimed: Valence=None

100.0
% of subjects
95% Confidence Interval: 95.8 to 100.0

Unprimed: Valence=Tetravalent

Unprimed: Valence=Trivalent

F17 PI (M3)

Primed: Valence=Bivalent

1.1
% of subjects
95% Confidence Interval: 0.0 to 6.2

Primed: Valence=Monovalent

1.1
% of subjects
95% Confidence Interval: 0.0 to 6.2

Primed: Valence=None

1.1
% of subjects
95% Confidence Interval: 0.0 to 6.2

Primed: Valence=Tetravalent

96.6
% of subjects
95% Confidence Interval: 90.4 to 99.3

Primed: Valence=Trivalent

Unprimed: Valence=Bivalent

4.8
% of subjects
95% Confidence Interval: 1.3 to 11.9

Unprimed: Valence=Monovalent

24.1
% of subjects
95% Confidence Interval: 15.4 to 34.7

Unprimed: Valence=None

53.0
% of subjects
95% Confidence Interval: 41.7 to 64.1

Unprimed: Valence=Tetravalent

10.8
% of subjects
95% Confidence Interval: 5.1 to 19.6

Unprimed: Valence=Trivalent

7.2
% of subjects
95% Confidence Interval: 2.7 to 15.1

F17 PI (M6)

Primed: Valence=Bivalent

1.1
% of subjects
95% Confidence Interval: 0.0 to 6.2

Primed: Valence=Monovalent

1.1
% of subjects
95% Confidence Interval: 0.0 to 6.2

Primed: Valence=None

1.1
% of subjects
95% Confidence Interval: 0.0 to 6.2

Primed: Valence=Tetravalent

97.7
% of subjects
95% Confidence Interval: 91.9 to 99.7

Primed: Valence=Trivalent

Unprimed: Valence=Bivalent

7.3
% of subjects
95% Confidence Interval: 2.7 to 15.2

Unprimed: Valence=Monovalent

23.2
% of subjects
95% Confidence Interval: 14.6 to 33.8

Unprimed: Valence=None

52.4
% of subjects
95% Confidence Interval: 41.1 to 63.6

Unprimed: Valence=Tetravalent

9.8
% of subjects
95% Confidence Interval: 4.3 to 18.3

Unprimed: Valence=Trivalent

7.3
% of subjects
95% Confidence Interval: 2.7 to 15.2

F17 PII (M7)

Primed: Valence=Bivalent

Primed: Valence=Monovalent

Primed: Valence=None

Primed: Valence=Tetravalent

100.0
% of subjects
95% Confidence Interval: 95.8 to 100.0

Primed: Valence=Trivalent

Unprimed: Valence=Bivalent

2.4
% of subjects
95% Confidence Interval: 0.3 to 8.5

Unprimed: Valence=Monovalent

1.2
% of subjects
95% Confidence Interval: 0.0 to 6.6

Unprimed: Valence=None

2.4
% of subjects
95% Confidence Interval: 0.3 to 8.5

Unprimed: Valence=Tetravalent

86.6
% of subjects
95% Confidence Interval: 77.3 to 93.1

Unprimed: Valence=Trivalent

7.3
% of subjects
95% Confidence Interval: 2.7 to 15.2

F19: Pre-vaccination

Primed: Valence=Bivalent

3.2
% of subjects
95% Confidence Interval: 0.7 to 9.0

Primed: Valence=Monovalent

2.1
% of subjects
95% Confidence Interval: 0.3 to 7.5

Primed: Valence=None

Primed: Valence=Tetravalent

92.6
% of subjects
95% Confidence Interval: 85.3 to 97.0

Primed: Valence=Trivalent

2.1
% of subjects
95% Confidence Interval: 0.3 to 7.5

Unprimed: Valence=Bivalent

Unprimed: Valence=Monovalent

Unprimed: Valence=None

100.0
% of subjects
95% Confidence Interval: 94.1 to 100.0

Unprimed: Valence=Tetravalent

Unprimed: Valence=Trivalent

F19 PI (M3)

Primed: Valence=Bivalent

Primed: Valence=Monovalent

Primed: Valence=None

1.1
% of subjects
95% Confidence Interval: 0.0 to 5.8

Primed: Valence=Tetravalent

98.9
% of subjects
95% Confidence Interval: 94.2 to 100.0

Primed: Valence=Trivalent

Unprimed: Valence=Bivalent

5.0
% of subjects
95% Confidence Interval: 1.0 to 13.9

Unprimed: Valence=Monovalent

23.3
% of subjects
95% Confidence Interval: 13.4 to 36.0

Unprimed: Valence=None

50.0
% of subjects
95% Confidence Interval: 36.8 to 63.2

Unprimed: Valence=Tetravalent

20.0
% of subjects
95% Confidence Interval: 10.8 to 32.3

Unprimed: Valence=Trivalent

1.7
% of subjects
95% Confidence Interval: 0.0 to 8.9

F19 PI (M6)

Primed: Valence=Bivalent

Primed: Valence=Monovalent

Primed: Valence=None

Primed: Valence=Tetravalent

100.0
% of subjects
95% Confidence Interval: 96.0 to 100.0

Primed: Valence=Trivalent

Unprimed: Valence=Bivalent

5.1
% of subjects
95% Confidence Interval: 1.1 to 14.1

Unprimed: Valence=Monovalent

27.1
% of subjects
95% Confidence Interval: 16.4 to 40.3

Unprimed: Valence=None

50.8
% of subjects
95% Confidence Interval: 37.5 to 64.1

Unprimed: Valence=Tetravalent

13.6
% of subjects
95% Confidence Interval: 6.0 to 25.0

Unprimed: Valence=Trivalent

3.4
% of subjects
95% Confidence Interval: 0.4 to 11.7

F19 PII (M7)

Primed: Valence=Bivalent

Primed: Valence=Monovalent

1.1
% of subjects
95% Confidence Interval: 0.0 to 6.0

Primed: Valence=None

Primed: Valence=Tetravalent

98.9
% of subjects
95% Confidence Interval: 94.0 to 100.0

Primed: Valence=Trivalent

Unprimed: Valence=Bivalent

8.5
% of subjects
95% Confidence Interval: 2.8 to 18.7

Unprimed: Valence=Monovalent

5.1
% of subjects
95% Confidence Interval: 1.1 to 14.1

Unprimed: Valence=None

5.1
% of subjects
95% Confidence Interval: 1.1 to 14.1

Unprimed: Valence=Tetravalent

74.6
% of subjects
95% Confidence Interval: 61.6 to 85.0

Unprimed: Valence=Trivalent

6.8
% of subjects
95% Confidence Interval: 1.9 to 16.5

Placebo: Pre-vaccination

Primed: Valence=Bivalent

1.0
% of subjects
95% Confidence Interval: 0.0 to 5.4

Primed: Valence=Monovalent

8.9
% of subjects
95% Confidence Interval: 4.2 to 16.2

Primed: Valence=None

Primed: Valence=Tetravalent

90.1
% of subjects
95% Confidence Interval: 82.5 to 95.1

Primed: Valence=Trivalent

Unprimed: Valence=Bivalent

Unprimed: Valence=Monovalent

Unprimed: Valence=None

100.0
% of subjects
95% Confidence Interval: 95.1 to 100.0

Unprimed: Valence=Tetravalent

Unprimed: Valence=Trivalent

Placebo: PI (M3)

Primed: Valence=Bivalent

2.0
% of subjects
95% Confidence Interval: 0.2 to 7.1

Primed: Valence=Monovalent

3.0
% of subjects
95% Confidence Interval: 0.6 to 8.6

Primed: Valence=None

3.0
% of subjects
95% Confidence Interval: 0.6 to 8.6

Primed: Valence=Tetravalent

91.9
% of subjects
95% Confidence Interval: 84.7 to 96.4

Primed: Valence=Trivalent

Unprimed: Valence=Bivalent

Unprimed: Valence=Monovalent

Unprimed: Valence=None

95.8
% of subjects
95% Confidence Interval: 88.1 to 99.1

Unprimed: Valence=Tetravalent

4.2
% of subjects
95% Confidence Interval: 0.9 to 11.9

Unprimed: Valence=Trivalent

Placebo: PI (M6)

Primed: Valence=Bivalent

Primed: Valence=Monovalent

3.0
% of subjects
95% Confidence Interval: 0.6 to 8.6

Primed: Valence=None

5.1
% of subjects
95% Confidence Interval: 1.7 to 11.4

Primed: Valence=Tetravalent

89.9
% of subjects
95% Confidence Interval: 82.2 to 95.0

Primed: Valence=Trivalent

2.0
% of subjects
95% Confidence Interval: 0.2 to 7.1

Unprimed: Valence=Bivalent

2.9
% of subjects
95% Confidence Interval: 0.4 to 10.1

Unprimed: Valence=Monovalent

1.4
% of subjects
95% Confidence Interval: 0.0 to 7.8

Unprimed: Valence=None

92.8
% of subjects
95% Confidence Interval: 83.9 to 97.6

Unprimed: Valence=Tetravalent

2.9
% of subjects
95% Confidence Interval: 0.4 to 10.1

Unprimed: Valence=Trivalent

Placebo: PII (M7)

Primed: Valence=Bivalent

1.0
% of subjects
95% Confidence Interval: 0.0 to 5.5

Primed: Valence=Monovalent

2.0
% of subjects
95% Confidence Interval: 0.2 to 7.1

Primed: Valence=None

5.1
% of subjects
95% Confidence Interval: 1.7 to 11.4

Primed: Valence=Tetravalent

90.9
% of subjects
95% Confidence Interval: 84.4 to 95.8

Primed: Valence=Trivalent

1.0
% of subjects
95% Confidence Interval: 0.0 to 5.5

Unprimed: Valence=Bivalent

1.5
% of subjects
95% Confidence Interval: 0.0 to 7.9

Unprimed: Valence=Monovalent

1.5
% of subjects
95% Confidence Interval: 0.0 to 7.9

Unprimed: Valence=None

94.1
% of subjects
95% Confidence Interval: 85.6 to 98.4

Unprimed: Valence=Tetravalent

2.9
% of subjects
95% Confidence Interval: 0.4 to 10.2

Unprimed: Valence=Trivalent

Percent of Subjects With Neut. Sero-response to Each DEN Serotype

Seropositivity rates for DEN neut. antibodies for unprimed and primed subjects

F17: Pre-vaccination

Primed: DEN-1, >10 ED50

97.8
percent of subject with attribute
95% Confidence Interval: 92.3 to 99.7

Primed: DEN-2, >10 ED50

97.8
percent of subject with attribute
95% Confidence Interval: 92.3 to 99.7

Primed: DEN-3, >10 ED50

96.7
percent of subject with attribute
95% Confidence Interval: 90.7 to 99.3

Primed: DEN-4, >10 ED50

96.7
percent of subject with attribute
95% Confidence Interval: 90.7 to 99.3

Unprimed: DEN-1, >10 ED50

Unprimed: DEN-2, >10 ED50

Unprimed: DEN-3, >10 ED50

Unprimed: DEN-4, >10 ED50

F17 PI (M3)

Primed: DEN-1, >10 ED50

97.7
percent of subject with attribute
95% Confidence Interval: 92.0 to 99.7

Primed: DEN-2, >10 ED50

96.6
percent of subject with attribute
95% Confidence Interval: 90.4 to 99.3

Primed: DEN-3, >10 ED50

96.6
percent of subject with attribute
95% Confidence Interval: 90.4 to 99.3

Primed: DEN-4, >10 ED50

98.9
percent of subject with attribute
95% Confidence Interval: 93.8 to 100.0

Unprimed: DEN-1, >10 ED50

20.5
percent of subject with attribute
95% Confidence Interval: 12.4 to 30.8

Unprimed: DEN-2, >10 ED50

26.5
percent of subject with attribute
95% Confidence Interval: 17.4 to 37.3

Unprimed: DEN-3, >10 ED50

14.5
percent of subject with attribute
95% Confidence Interval: 7.7 to 23.9

Unprimed: DEN-4, >10 ED50

37.3
percent of subject with attribute
95% Confidence Interval: 27.0 to 48.7

F17 PI (M6)

Primed: DEN-1, >10 ED50

98.9
percent of subject with attribute
95% Confidence Interval: 93.8 to 100.0

Primed: DEN-2, >10 ED50

97.7
percent of subject with attribute
95% Confidence Interval: 91.9 to 99.7

Primed: DEN-3, >10 ED50

97.7
percent of subject with attribute
95% Confidence Interval: 91.9 to 99.7

Primed: DEN-4, >10 ED50

98.9
percent of subject with attribute
95% Confidence Interval: 93.8 to 100.0

Unprimed: DEN-1, >10 ED50

22.0
percent of subject with attribute
95% Confidence Interval: 13.6 to 32.5

Unprimed: DEN-2, >10 ED50

28.0
percent of subject with attribute
95% Confidence Interval: 18.7 to 39.1

Unprimed: DEN-3, >10 ED50

15.9
percent of subject with attribute
95% Confidence Interval: 8.7 to 25.6

Unprimed: DEN-4, >10 ED50

32.9
percent of subject with attribute
95% Confidence Interval: 22.9 to 44.2

F17 PII (M7)

Primed: DEN-1, >10 ED50

100.0
percent of subject with attribute
95% Confidence Interval: 95.8 to 100.0

Primed: DEN-2, >10 ED50

100.0
percent of subject with attribute
95% Confidence Interval: 95.8 to 100.0

Primed: DEN-3, >10 ED50

100.0
percent of subject with attribute
95% Confidence Interval: 95.8 to 100.0

Primed: DEN-4, >10 ED50

100.0
percent of subject with attribute
95% Confidence Interval: 95.8 to 100.0

Unprimed: DEN-1, >10 ED50

95.1
percent of subject with attribute
95% Confidence Interval: 88.0 to 98.7

Unprimed: DEN-2, >10 ED50

89.0
percent of subject with attribute
95% Confidence Interval: 80.2 to 94.9

Unprimed: DEN-3, >10 ED50

92.7
percent of subject with attribute
95% Confidence Interval: 84.8 to 97.3

Unprimed: DEN-4, >10 ED50

97.6
percent of subject with attribute
95% Confidence Interval: 91.5 to 99.7

F19: Pre-vaccination

Primed: DEN-1, >10 ED50

96.8
percent of subject with attribute
95% Confidence Interval: 91.0 to 99.3

Primed: DEN-2, >10 ED50

96.8
percent of subject with attribute
95% Confidence Interval: 91.0 to 99.3

Primed: DEN-3, >10 ED50

92.6
percent of subject with attribute
95% Confidence Interval: 85.3 to 97.0

Primed: DEN-4, >10 ED50

98.9
percent of subject with attribute
95% Confidence Interval: 94.2 to 100.0

Unprimed: DEN-1, >10 ED50

Unprimed: DEN-2, >10 ED50

Unprimed: DEN-3, >10 ED50

Unprimed: DEN-4, >10 ED50

F19 PI (M3)

Primed: DEN-1, >10 ED50

98.9
percent of subject with attribute
95% Confidence Interval: 94.2 to 100.0

Primed: DEN-2, >10 ED50

98.9
percent of subject with attribute
95% Confidence Interval: 94.2 to 100.0

Primed: DEN-3, >10 ED50

98.9
percent of subject with attribute
95% Confidence Interval: 94.2 to 100.0

Primed: DEN-4, >10 ED50

98.9
percent of subject with attribute
95% Confidence Interval: 94.2 to 100.0

Unprimed: DEN-1, >10 ED50

26.7
percent of subject with attribute
95% Confidence Interval: 16.1 to 39.7

Unprimed: DEN-2, >10 ED50

43.3
percent of subject with attribute
95% Confidence Interval: 30.6 to 56.8

Unprimed: DEN-3, >10 ED50

21.7
percent of subject with attribute
95% Confidence Interval: 12.1 to 34.2

Unprimed: DEN-4, >10 ED50

26.7
percent of subject with attribute
95% Confidence Interval: 16.1 to 39.7

F19 PI (M6)

Primed: DEN-1, >10 ED50

100.0
percent of subject with attribute
95% Confidence Interval: 96.0 to 100.0

Primed: DEN-2, >10 ED50

100.0
percent of subject with attribute
95% Confidence Interval: 96.0 to 100.0

Primed: DEN-3, >10 ED50

100.0
percent of subject with attribute
95% Confidence Interval: 96.0 to 100.0

Primed: DEN-4, >10 ED50

100.0
percent of subject with attribute
95% Confidence Interval: 96.0 to 100.0

Unprimed: DEN-1, >10 ED50

18.6
percent of subject with attribute
95% Confidence Interval: 9.7 to 30.9

Unprimed: DEN-2, >10 ED50

40.7
percent of subject with attribute
95% Confidence Interval: 28.1 to 54.3

Unprimed: DEN-3, >10 ED50

16.9
percent of subject with attribute
95% Confidence Interval: 8.4 to 29.0

Unprimed: DEN-4, >10 ED50

25.4
percent of subject with attribute
95% Confidence Interval: 15.0 to 38.4

F19 PII (M7)

Primed: DEN-1, >10 ED50

100.0
percent of subject with attribute
95% Confidence Interval: 96.0 to 100.0

Primed: DEN-2, >10 ED50

98.9
percent of subject with attribute
95% Confidence Interval: 94.0 to 100.0

Primed: DEN-3, >10 ED50

98.9
percent of subject with attribute
95% Confidence Interval: 94.0 to 100.0

Primed: DEN-4, >10 ED50

98.9
percent of subject with attribute
95% Confidence Interval: 94.0 to 100.0

Unprimed: DEN-1, >10 ED50

83.1
percent of subject with attribute
95% Confidence Interval: 71.0 to 91.6

Unprimed: DEN-2, >10 ED50

93.2
percent of subject with attribute
95% Confidence Interval: 83.5 to 98.1

Unprimed: DEN-3, >10 ED50

78.0
percent of subject with attribute
95% Confidence Interval: 65.3 to 87.7

Unprimed: DEN-4, >10 ED50

86.4
percent of subject with attribute
95% Confidence Interval: 75.0 to 94.0

Placebo: Pre-vaccination

Primed: DEN-1, >10 ED50

94.1
percent of subject with attribute
95% Confidence Interval: 87.5 to 97.8

Primed: DEN-2, >10 ED50

95.0
percent of subject with attribute
95% Confidence Interval: 88.8 to 98.4

Primed: DEN-3, >10 ED50

90.1
percent of subject with attribute
95% Confidence Interval: 82.5 to 95.1

Primed: DEN-4, >10 ED50

92.1
percent of subject with attribute
95% Confidence Interval: 85.0 to 96.5

Unprimed: DEN-1, >10 ED50

Unprimed: DEN-2, >10 ED50

Unprimed: DEN-3, >10 ED50

Unprimed: DEN-4, >10 ED50

Placebo: PI (M3)

Primed: DEN-1, >10 ED50

94.9
percent of subject with attribute
95% Confidence Interval: 88.6 to 98.3

Primed: DEN-2, >10 ED50

93.9
percent of subject with attribute
95% Confidence Interval: 87.3 to 97.7

Primed: DEN-3, >10 ED50

91.9
percent of subject with attribute
95% Confidence Interval: 84.7 to 96.4

Primed: DEN-4, >10 ED50

93.9
percent of subject with attribute
95% Confidence Interval: 87.3 to 97.7

Unprimed: DEN-1, >10 ED50

4.2
percent of subject with attribute
95% Confidence Interval: 0.9 to 11.9

Unprimed: DEN-2, >10 ED50

4.2
percent of subject with attribute
95% Confidence Interval: 0.9 to 11.9

Unprimed: DEN-3, >10 ED50

4.2
percent of subject with attribute
95% Confidence Interval: 0.9 to 11.9

Unprimed: DEN-4, >10 ED50

4.2
percent of subject with attribute
95% Confidence Interval: 0.9 to 11.9

Placebo: PI (M6)

Primed: DEN-1, >10 ED50

92.9
percent of subject with attribute
95% Confidence Interval: 86.0 to 97.1

Primed: DEN-2, >10 ED50

92.9
percent of subject with attribute
95% Confidence Interval: 86.0 to 97.1

Primed: DEN-3, >10 ED50

90.9
percent of subject with attribute
95% Confidence Interval: 83.4 to 95.8

Primed: DEN-4, >10 ED50

91.9
percent of subject with attribute
95% Confidence Interval: 84.7 to 96.4

Unprimed: DEN-1, >10 ED50

4.3
percent of subject with attribute
95% Confidence Interval: 0.9 to 12.2

Unprimed: DEN-2, >10 ED50

4.3
percent of subject with attribute
95% Confidence Interval: 0.9 to 12.2

Unprimed: DEN-3, >10 ED50

7.2
percent of subject with attribute
95% Confidence Interval: 2.4 to 16.1

Unprimed: DEN-4, >10 ED50

2.9
percent of subject with attribute
95% Confidence Interval: 0.4 to 10.1

Placebo: PII (M7)

Primed: DEN-1, >10 ED50

90.9
percent of subject with attribute
95% Confidence Interval: 83.4 to 95.8

Primed: DEN-2, >10 ED50

93.9
percent of subject with attribute
95% Confidence Interval: 87.3 to 97.7

Primed: DEN-3, >10 ED50

92.9
percent of subject with attribute
95% Confidence Interval: 86.0 to 97.1

Primed: DEN-4, >10 ED50

92.9
percent of subject with attribute
95% Confidence Interval: 86.0 to 97.1

Unprimed: DEN-1, >10 ED50

4.4
percent of subject with attribute
95% Confidence Interval: 0.9 to 12.4

Unprimed: DEN-2, >10 ED50

2.9
percent of subject with attribute
95% Confidence Interval: 0.4 to 10.2

Unprimed: DEN-3, >10 ED50

4.4
percent of subject with attribute
95% Confidence Interval: 0.9 to 12.4

Unprimed: DEN-4, >10 ED50

4.4
percent of subject with attribute
95% Confidence Interval: 0.9 to 12.4

Vaccine Response to DEN Antibody at Post Dose 1, Month 3

Vaccine response for DEN-1, DEN-2, DEN-3 and DEN-4 antibody S- = seronegative subjects (antibody titer <10 ED50 for DEN-1, 2, 3, and 4 prior to vaccination; S+ = Seropositive subjects (antibody titer >10 ED50 for DEN-1, 2, 3 and 4 prior to vaccination; Total = subjects either seropositive or seronegative at pre-vaccination Vaccine response defined as: For initially seronegative subjects, antibody titer >10 ED50 at PI(M3) and for initially seropositive subjects: antibody titer at PI(m3) >4 fold the pre-vaccination antibody titer

DEN-1, Placebo, Total

7.5
% of subjects
95% Confidence Interval: 3.5 to 13.8

DEN-2, F17, S-

25.9
% of subjects
95% Confidence Interval: 17.0 to 36.5

DEN-2, F17, S+

63.6
% of subjects
95% Confidence Interval: 45.1 to 79.6

DEN-2, F17, Total

36.4
% of subjects
95% Confidence Interval: 27.8 to 45.8

DEN-2, F19, S-

46.0
% of subjects
95% Confidence Interval: 33.4 to 59.1

DEN-2, F19, S+

64.4
% of subjects
95% Confidence Interval: 48.8 to 78.1

DEN-2, F19, Total

53.7
% of subjects
95% Confidence Interval: 43.8 to 63.3

DEN-2, Placebo, S-

3.9
% of subjects
95% Confidence Interval: 0.8 to 11.1

DEN-2, Placebo, S+

14.0
% of subjects
95% Confidence Interval: 5.3 to 27.9

DEN-2, Placebo, Total

7.6
% of subjects
95% Confidence Interval: 3.5 to 13.9

DEN-3, F17, S-

15.3
% of subjects
95% Confidence Interval: 8.4 to 24.7

DEN-3, F17, S+

61.1
% of subjects
95% Confidence Interval: 43.5 to 76.9

DEN-3, F17, Total

28.9
% of subjects
95% Confidence Interval: 21.0 to 37.9

DEN-3, F19, S-

28.8
% of subjects
95% Confidence Interval: 18.3 to 41.3

DEN-3, F19, S+

62.2
% of subjects
95% Confidence Interval: 46.5 to 76.2

DEN-3, F19, Total

42.3
% of subjects
95% Confidence Interval: 33.0 to 52.1

DEN-3, Placebo, S-

6.2
% of subjects
95% Confidence Interval: 2.0 to 13.8

DEN-3, Placebo, S+

5.1
% of subjects
95% Confidence Interval: 0.6 to 17.3

DEN-3, Placebo, Total

5.8
% of subjects
95% Confidence Interval: 2.4 to 11.6

DEN-4, F17, S-

38.8
% of subjects
95% Confidence Interval: 28.4 to 50.0

DEN-4, F17, S+

52.4
% of subjects
95% Confidence Interval: 36.4 to 68.0

DEN-4, F17, Total

43.3
% of subjects
95% Confidence Interval: 34.5 to 52.4

DEN-4, F19, S-

27.9
% of subjects
95% Confidence Interval: 17.1 to 40.8

DEN-4, F19, S+

65.3
% of subjects
95% Confidence Interval: 50.4 to 78.3

DEN-4, F19, Total

44.5
% of subjects
95% Confidence Interval: 35.1 to 54.3

DEN-4, Placebo, S-

7.6
% of subjects
95% Confidence Interval: 2.8 to 15.8

DEN-4, Placebo, S+

11.1
% of subjects
95% Confidence Interval: 3.7 to 24.1

DEN-4, Placebo, Total

8.9
% of subjects
95% Confidence Interval: 4.5 to 15.3

DEN-1, F17, S-

20.2
% of subjects
95% Confidence Interval: 12.3 to 30.4

DEN-1, F17, S+

54.1
% of subjects
95% Confidence Interval: 36.9 to 70.5

DEN-1, F17, Total

30.6
% of subjects
95% Confidence Interval: 22.5 to 39.6

DEN-1, F19, S-

30.2
% of subjects
95% Confidence Interval: 19.2 to 43.0

DEN-1, F19, S+

73.7
% of subjects
95% Confidence Interval: 56.9 to 86.6

DEN-1, F19, Total

46.5
% of subjects
95% Confidence Interval: 36.5 to 56.7

DEN-1, Placebo, S-

7.8
% of subjects
95% Confidence Interval: 2.9 to 16.2

DEN-1, Placebo, S+

7.0
% of subjects
95% Confidence Interval: 1.5 to 19.1

Vaccine Response to DEN Antibody at Post Dose 2, Month 7

Vaccine response for DEN-1, DEN2, DEN-3, DEN-4 antibody at post dose 2, month 7

DEN-1, F17, S-

95.2
% of subjects
95% Confidence Interval: 88.1 to 98.7

DEN-1, F17, S+

60.0
% of subjects
95% Confidence Interval: 42.1 to 76.1

DEN-1, F17, Total

84.7
% of subjects
95% Confidence Interval: 77.0 to 90.7

DEN-1, F19, S-

83.6
% of subjects
95% Confidence Interval: 71.9 to 91.8

DEN-1, F19, S+

75.7
% of subjects
95% Confidence Interval: 58.8 to 88.2

DEN-1, F19, Total

80.6
% of subjects
95% Confidence Interval: 71.4 to 87.9

DEN-1, Placebo, S-

6.8
% of subjects
95% Confidence Interval: 2.2 to 15.1

DEN-1, Placebo, S+

11.6
% of subjects
95% Confidence Interval: 3.9 to 25.1

DEN-1, Placebo, Total

8.5
% of subjects
95% Confidence Interval: 4.2 to 15.2

DEN-2, F17, S-

89.3
% of subjects
95% Confidence Interval: 80.6 to 95.0

DEN-2, F17, S+

71.9
% of subjects
95% Confidence Interval: 53.3 to 86.3

DEN-2, F17, Total

84.5
% of subjects
95% Confidence Interval: 76.6 to 90.5

DEN-2, F19, S-

93.5
% of subjects
95% Confidence Interval: 84.3 to 98.2

DEN-2, F19, S+

64.3
% of subjects
95% Confidence Interval: 48.0 to 78.4

DEN-2, F19, Total

81.7
% of subjects
95% Confidence Interval: 72.9 to 88.6

DEN-2, Placebo, S-

4.1
% of subjects
95% Confidence Interval: 0.9 to 11.5

DEN-2, Placebo, S+

14.0
% of subjects
95% Confidence Interval: 5.3 to 27.9

DEN-2, Placebo, Total

7.8
% of subjects
95% Confidence Interval: 3.6 to 14.2

DEN-3, F17, S-

92.9
% of subjects
95% Confidence Interval: 85.1 to 97.3

DEN-3, F17, S+

47.1
% of subjects
95% Confidence Interval: 29.8 to 64.9

DEN-3, F17, Total

79.7
% of subjects
95% Confidence Interval: 71.3 to 86.5

DEN-3, F19, S-

79.7
% of subjects
95% Confidence Interval: 67.8 to 88.7

DEN-3, F19, S+

48.8
% of subjects
95% Confidence Interval: 33.3 to 64.5

DEN-3, F19, Total

67.3
% of subjects
95% Confidence Interval: 57.5 to 76.0

DEN-3, Placebo, S-

9.0
% of subjects
95% Confidence Interval: 3.7 to 17.6

DEN-3, Placebo, S+

15.4
% of subjects
95% Confidence Interval: 5.9 to 30.5

DEN-3, Placebo, Total

11.1
% of subjects
95% Confidence Interval: 6.1 to 18.3

DEN-4, F17, S-

97.6
% of subjects
95% Confidence Interval: 91.7 to 99.7

DEN-4, F17, S+

57.5
% of subjects
95% Confidence Interval: 40.9 to 73.0

DEN-4, F17, Total

84.7
% of subjects
95% Confidence Interval: 77.1 to 90.5

DEN-4, F19, S-

86.7
% of subjects
95% Confidence Interval: 75.4 to 94.1

DEN-4, F19, S+

68.8
% of subjects
95% Confidence Interval: 53.7 to 81.3

DEN-4, F19, Total

78.7
% of subjects
95% Confidence Interval: 69.8 to 86.0

DEN-4, Placebo, S-

7.9
% of subjects
95% Confidence Interval: 3.0 to 16.4

DEN-4, Placebo, S+

6.7
% of subjects
95% Confidence Interval: 1.4 to 18.3

DEN-4, Placebo, Total

7.4
% of subjects
95% Confidence Interval: 3.5 to 13.7

Total

636
Participants

Age, Continuous

13.4
years (Mean)
Standard Deviation: 13.50

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

Region of Enrollment

Sex: Female, Male

Overall Study

T-DEN-Post-Transfection F17

T-DEN-Post-Transfection F19

Placebo

Drop/Withdrawal Reasons

T-DEN-Post-Transfection F17

T-DEN-Post-Transfection F19

Placebo