Immunogenicity and Safety of Three Formulations of Dengue Vaccines in Healthy Adults Aged 18 to 45 Years in the US
Sponsor
Sanofi (Industry)
Overall Status
Completed
CT.gov ID
NCT00617344
Collaborator
(none)
260
5
3
21.5
52
2.4
Study Details
Study Description
Brief Summary
This study used 3 different formulations of tetravalent CYD dengue vaccine.
The primary objective of the study was to evaluate the neutralizing antibody response after 2 doses of two different formulations of tetravalent dengue vaccine administered at Month 0 and Month 6.
The secondary objectives were:
-
To evaluate the safety of the 3 formulations of tetravalent CYD dengue vaccine.
-
To describe the neutralizing antibody responses to each of the 3 vaccine formulations.
-
To describe vaccine viremia after the first and second dose of each of the 3 vaccine formulations in a subset of participants.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
All participants provided blood samples for immunogenicity assessments, while vaccine viremia was assessed in a subset of participants in each group.
Safety was assessed in all participants as follows: solicited adverse event (AE) prelisted in the diary card were collected for 7 days after vaccination for solicited injection site reactions and 14 days for solicited systemic reactions , unsolicited AEs were collected for 28 days after vaccination, and serious adverse event (SAE) information collected throughout the study up to 6 months after vaccination.
Study Design
Study Type:
Interventional
Actual Enrollment
:
260 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Prevention
Official Title:
Immunogenicity and Safety of Three Tetravalent Formulations of Dengue Vaccine Candidates in Healthy Adults Aged 18 to 45 Years in the US
Actual Study Start Date
:
Apr 17, 2008
Actual Primary Completion Date
:
Dec 1, 2009
Actual Study Completion Date
:
Feb 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CYD Dengue Vaccine 5555 Formulation Participants received 3 doses of CYD dengue vaccine (5555 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. |
Biological: Tetravalent CYD Dengue Vaccine , 5555 formulation
A 0.5 mL dose, Subcutaneous at 0, 6, and 12 months, respectively.
|
| Experimental: CYD Dengue Vaccine 5553 Formulation Participants received 3 doses of CYD dengue vaccine (5553 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. |
Biological: Tetravalent CYD Dengue Vaccine , 5553 formulation
A 0.5 mL dose, Subcutaneous at 0, 6, and 12 months, respectively
|
| Experimental: CYD Dengue Vaccine 4444 Formulation Participants received 3 doses of CYD dengue vaccine (4444 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. |
Biological: Tetravalent CYD Dengue Vaccine, 4444 formulation
A 0.5 mL dose, Subcutaneous at 0, 6, and 12 months, respectively
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Antibody Titers of >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain: CYD Vaccine 5555 and 5553 Formulation [Pre-injection 1 (Day 0), 30 days post-injection 2 (Month 7)]
Percentage of participants with antibody titers >= 10 (1/dil) against each serotypes (1, 2, 3 and 4) of the dengue virus strains was assessed by dengue plaque reduction neutralization test (PRNT).
Secondary Outcome Measures
- Percentage of Participants With Antibody Titers of >=10 1/Dil Against Each Dengue Virus Serotype Strain [Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13)]
Percentage of participants with antibody titers >= 10 1/dil against each serotypes (1, 2, 3 and 4) of the dengue virus strains was assessed by PRNT.
- Percentage of Participants With Antibody Titers >=10 1/Dil Against At Least Any 1, 2, 3 or All 4 Dengue Virus Serotypes [Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13)]
Percentage of participants with antibody titers >= 10 1/dil against each serotypes (1, 2, 3 and 4) of the dengue virus strains was assessed by PRNT. In this outcome measure, participants with antibody titers >= 10 1/dil against any 1 of the 4 serotypes or any 2 of the 4 serotypes or any 3 of the 4 serotypes or with all 4 serotypes were reported.
- Geometric Means of Titers of Antibodies Against Each Dengue Virus Serotype Strain [Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13)]
Geometric mean titers against each dengue virus serotype (1, 2, 3 and 4) strain was measured by PRNT.
- Number of Participants With Solicited Injection Site Reactions After Any Vaccination [7 days after any injection 1, 2 or 3]
Solicited injection site reactions: Pain, Erythema, and Swelling. Pain: Grade 1: Easily tolerated, Grade 2: Sufficiently discomforting to interfere with normal behavior or activities, Grade 3: Incapacitating, unable to perform usual activities. Erythema:- Grade 1: <2.5 cm, Grade 2: >=2.5 to <5 cm, Grade 3: >=5 cm. Swelling:- Grade 1: <2.5 cm, Grade 2: >=2.5 to <5 cm, Grade 3: >=5 cm.
- Number of Participants With Solicited Systemic Reactions After Any Vaccination [14 days after any injection 1, 2 or 3]
Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Fever: - Grade1: >=37.5°C to <=38.0°C (>=99.5°F to <=100.4°F), Grade 2: >38.0°C to <=39.0°C (>100.4°F to <= 102.2°F), Grade 3: >39.0°C (>102.2°F). Headache, malaise, myalgia and asthenia: Grade 1: noticeable but does not interfere with daily activities, Grade 2: interferes with daily activities, Grade 3: prevents daily activities.
- Number of Participants With Vaccine Viremia [7 days post-injection 1 and 2, 14 days post-injection 1 and 2]
Vaccine viremia (level of vaccine virus in blood samples taken from participants) was measured by an assay yellow fever reverse transcriptase polymerase chain reaction which allowed the detection of vaccine viremia of any serotype (1, 2, 3 and 4).
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 45 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
Healthy, as determined by medical history, clinical examination, and biological safety parameters.
-
Aged 18 to 45 years on the day of inclusion.
-
Provision of informed consent signed by the participant or another legally acceptable representative.
-
For a woman of child-bearing potential, use of an effective method of contraception or abstinence for at least 4 weeks prior to the first vaccination, and until at least 4 weeks after the last study vaccination.
-
Able to attend all scheduled visits and to comply with all trial procedures.
Exclusion Criteria:
-
Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia.
-
For a woman of child-bearing potential, known or suspected pregnancy or positive serum/urine pregnancy test.
-
Breast-feeding woman.
-
Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination.
-
Planned participation in another clinical trial during the present trial period.
-
Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term (at least 2 weeks within the previous 3 months) systemic corticosteroids therapy (at a dose of at least 10 mg). Topical steroids were allowed.
-
Known systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to the trial vaccine or to a vaccine containing any of the same substances.
-
Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the investigator.
-
Current or past alcohol abuse or drug addiction that may interfere with the participant's ability to comply with trial procedures.
-
Receipt of blood or blood-derived products in the past 3 months, that might interfere with the assessment of immune response.
-
Receipt of any vaccine in the 4 weeks preceding the first trial vaccination.
-
Planned receipt of any vaccine in the 4 weeks following each of the trial vaccinations.
-
Human Immunodeficiency Virus (HIV), hepatitis B surface antigen, or hepatitis C virus seropositivity in blood sample taken at Screening.
-
Participant deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent.
-
Clinically significant laboratory test abnormalities (as determined by the investigator) in blood sample taken at Screening.
-
Previous residence in, travel or planned travel of more than 2 weeks during the study period to areas with high dengue infection endemicity.
-
Reported history of flavivirus infection as reported by the participant.
-
Previous vaccination against flavivirus diseases (including Japanese encephalitis, tick-borne encephalitis, and yellow fever).
-
Flavivirus vaccination planned during the trial period.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Investigational Site 004 | Hoover | Alabama | United States | 35126 |
| 2 | Investigational Site 002 | San Diego | California | United States | 92103 |
| 3 | Investigational Site 005 | Vallejo | California | United States | 94589 |
| 4 | Investigational Site 001 | New Orleans | Louisiana | United States | 70119 |
| 5 | Investigational Site 003 | Springfield | Missouri | United States | 65802 |
Sponsors and Collaborators
- Sanofi
Investigators
- Study Director: Clinical Sciences & Operations, Sanofi Pasteur, a Sanofi Company
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Sanofi
ClinicalTrials.gov Identifier:
NCT00617344
Other Study ID Numbers:
- CYD12
First Posted:
Feb 18, 2008
Last Update Posted:
Jun 11, 2019
Last Verified:
May 1, 2019
Keywords provided by Sanofi
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Study participants were enrolled from 17 April 2008 to 04 June 2008 at 5 sites in the United States. |
|---|---|
| Pre-assignment Detail | A total of 309 participants were screened in the study, out of which 260 participants were enrolled and vaccinated in the study. Screen failures were mainly due to inclusion criteria not met or exclusion criteria met. |
| Arm/Group Title | CYD Dengue Vaccine 5555 Formulation | CYD Dengue Vaccine 5553 Formulation | CYD Dengue Vaccine 4444 Formulation |
|---|---|---|---|
| Arm/Group Description | Participants received 3 doses of CYD dengue vaccine (5555 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Participants received 3 doses of CYD dengue vaccine (5553 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Participants received 3 doses of CYD dengue vaccine (4444 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. |
| Period Title: Overall Study | |||
| STARTED | 104 | 103 | 53 |
| Received Vaccination 1 | 104 | 103 | 53 |
| Received Vaccination 2 | 86 | 85 | 46 |
| Received Vaccination 3 | 79 | 81 | 45 |
| COMPLETED | 79 | 81 | 45 |
| NOT COMPLETED | 25 | 22 | 8 |
Baseline Characteristics
| Arm/Group Title | CYD Dengue Vaccine 5555 Formulation | CYD Dengue Vaccine 5553 Formulation | CYD Dengue Vaccine 4444 Formulation | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants received 3 doses of CYD dengue vaccine (5555 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Participants received 3 doses of CYD dengue vaccine (5553 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Participants received 3 doses of CYD dengue vaccine (4444 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Total of all reporting groups |
| Overall Participants | 101 | 101 | 53 | 255 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
32.6
(8.78)
|
32.1
(8.57)
|
32.4
(8.04)
|
32.4
(8.52)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
61
60.4%
|
59
58.4%
|
32
60.4%
|
152
59.6%
|
| Male |
40
39.6%
|
42
41.6%
|
21
39.6%
|
103
40.4%
|
Outcome Measures
| Title | Percentage of Participants With Antibody Titers of >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain: CYD Vaccine 5555 and 5553 Formulation |
|---|---|
| Description | Percentage of participants with antibody titers >= 10 (1/dil) against each serotypes (1, 2, 3 and 4) of the dengue virus strains was assessed by dengue plaque reduction neutralization test (PRNT). |
| Time Frame | Pre-injection 1 (Day 0), 30 days post-injection 2 (Month 7) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on Full Analysis Set (FAS). Here, 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | CYD Dengue Vaccine 5555 Formulation | CYD Dengue Vaccine 5553 Formulation |
|---|---|---|
| Arm/Group Description | Participants received 3 doses of CYD dengue vaccine (5555 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Participants received 3 doses of CYD dengue vaccine (5553 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. |
| Measure Participants | 101 | 101 |
| Dengue Virus Serotype 1: Day 0 |
1.0
1%
|
3.0
3%
|
| Dengue Virus Serotype 1:30 days post injection-2 |
65.4
64.8%
|
81.0
80.2%
|
| Dengue Virus Serotype 2: Day 0 |
1.0
1%
|
3.0
3%
|
| Dengue Virus Serotype 2:30 days post-injection 2 |
80.2
79.4%
|
83.3
82.5%
|
| Dengue Virus Serotype 3: Day 0 |
15.8
15.6%
|
14.9
14.8%
|
| Dengue Virus Serotype 3:30 days post-injection 2 |
87.2
86.3%
|
92.9
92%
|
| Dengue Virus Serotype 4: Day 0 |
3.0
3%
|
6.9
6.8%
|
| Dengue Virus Serotype 4:30 days post-injection 2 |
89.7
88.8%
|
58.3
57.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CYD Dengue Vaccine 5555 Formulation, CYD Dengue Vaccine 5553 Formulation |
|---|---|---|
| Comments | Dengue Virus Serotype 1: Pre-injection 1 (Day 0) | |
| Type of Statistical Test | Other | |
| Comments | The associated 95% confidence intervals (CIs) for the point estimates and the differences were calculated using normal approximation. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | -2.0 | |
| Confidence Interval |
(2-Sided) 95% -7.44 to 2.84 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | CYD Dengue Vaccine 5555 Formulation, CYD Dengue Vaccine 5553 Formulation |
|---|---|---|
| Comments | Dengue Virus Serotype 1: 30 days post-injection 2 | |
| Type of Statistical Test | Other | |
| Comments | The associated 95% CIs for the point estimates and the differences were calculated using normal approximation. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | -15.5 | |
| Confidence Interval |
(2-Sided) 95% -28.4 to -2.00 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | CYD Dengue Vaccine 5555 Formulation, CYD Dengue Vaccine 5553 Formulation |
|---|---|---|
| Comments | Dengue Virus Serotype 2: Pre-injection 1 (Day 0) | |
| Type of Statistical Test | Other | |
| Comments | The associated 95% CIs for the point estimates and the differences were calculated using normal approximation. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | -2.0 | |
| Confidence Interval |
(2-Sided) 95% -7.44 to 2.84 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | CYD Dengue Vaccine 5555 Formulation, CYD Dengue Vaccine 5553 Formulation |
|---|---|---|
| Comments | Dengue Virus Serotype 2: 30 days post-injection 2 | |
| Type of Statistical Test | Other | |
| Comments | The associated 95% CIs for the point estimates and the differences were calculated using normal approximation. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | -3.1 | |
| Confidence Interval |
(2-Sided) 95% -15.0 to 8.75 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | CYD Dengue Vaccine 5555 Formulation, CYD Dengue Vaccine 5553 Formulation |
|---|---|---|
| Comments | Dengue Virus Serotype 3: Pre-injection 1 (Day 0) | |
| Type of Statistical Test | Other | |
| Comments | The associated 95% CIs for the point estimates and the differences were calculated using normal approximation. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | 1.0 | |
| Confidence Interval |
(2-Sided) 95% -9.09 to 11.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | CYD Dengue Vaccine 5555 Formulation, CYD Dengue Vaccine 5553 Formulation |
|---|---|---|
| Comments | Dengue Virus Serotype 3: 30 days post-injection 2 | |
| Type of Statistical Test | Other | |
| Comments | The associated 95% CIs for the point estimates and the differences were calculated using normal approximation. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | -5.7 | |
| Confidence Interval |
(2-Sided) 95% -15.6 to 3.81 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | CYD Dengue Vaccine 5555 Formulation, CYD Dengue Vaccine 5553 Formulation |
|---|---|---|
| Comments | Dengue Virus Serotype 4: Pre-injection 1 (Day 0) | |
| Type of Statistical Test | Other | |
| Comments | The associated 95% CIs for the point estimates and the differences were calculated using normal approximation. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | -4.0 | |
| Confidence Interval |
(2-Sided) 95% -10.9 to 2.49 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | CYD Dengue Vaccine 5555 Formulation, CYD Dengue Vaccine 5553 Formulation |
|---|---|---|
| Comments | Dengue Virus Serotype 4: 30 days post-injection 2 | |
| Type of Statistical Test | Other | |
| Comments | The associated 95% CIs for the point estimates and the differences were calculated using normal approximation. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | 31.4 | |
| Confidence Interval |
(2-Sided) 95% 18.2 to 43.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Antibody Titers of >=10 1/Dil Against Each Dengue Virus Serotype Strain |
|---|---|
| Description | Percentage of participants with antibody titers >= 10 1/dil against each serotypes (1, 2, 3 and 4) of the dengue virus strains was assessed by PRNT. |
| Time Frame | Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on FAS population. Here, 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | CYD Dengue Vaccine 5555 Formulation | CYD Dengue Vaccine 5553 Formulation | CYD Dengue Vaccine 4444 Formulation |
|---|---|---|---|
| Arm/Group Description | Participants received 3 doses of CYD dengue vaccine (5555 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Participants received 3 doses of CYD dengue vaccine (5553 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Participants received 3 doses of CYD dengue vaccine (4444 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. |
| Measure Participants | 101 | 101 | 53 |
| Dengue Virus Serotype 1: Day 0 |
1.0
1%
|
3.0
3%
|
3.8
7.2%
|
| Dengue Virus Serotype 1:30 days post-injection 1 |
33.7
33.4%
|
50.5
50%
|
26.4
49.8%
|
| Dengue Virus Serotype 1:30 days post-injection 2 |
65.4
64.8%
|
81.0
80.2%
|
58.7
110.8%
|
| Dengue Virus Serotype 1:30 days post-injection 3 |
71.0
70.3%
|
84.0
83.2%
|
64.4
121.5%
|
| Dengue Virus Serotype 2: Day 0 |
1.0
1%
|
3.0
3%
|
1.9
3.6%
|
| Dengue Virus Serotype 2:30 days post-injection 1 |
46.5
46%
|
64.4
63.8%
|
34.0
64.2%
|
| Dengue Virus Serotype 2:30 days post-injection 2 |
80.2
79.4%
|
83.3
82.5%
|
58.7
110.8%
|
| Dengue Virus Serotype 2:30 days post-injection 3 |
84.3
83.5%
|
88.9
88%
|
77.8
146.8%
|
| Dengue Virus Serotype 3: Day 0 |
15.8
15.6%
|
14.9
14.8%
|
13.2
24.9%
|
| Dengue Virus Serotype 3:30 days post-injection 1 |
79.2
78.4%
|
80.2
79.4%
|
60.4
114%
|
| Dengue Virus Serotype 3:30 days post-injection 2 |
87.2
86.3%
|
92.9
92%
|
78.3
147.7%
|
| Dengue Virus Serotype 3:30 days post-injection 3 |
88.6
87.7%
|
98.8
97.8%
|
82.2
155.1%
|
| Dengue Virus Serotype 4: Day 0 |
3.0
3%
|
6.9
6.8%
|
5.7
10.8%
|
| Dengue Virus Serotype 4:30 days post-injection 1 |
84.2
83.4%
|
37.6
37.2%
|
94.3
177.9%
|
| Dengue Virus Serotype 4:30 days post-injection 2 |
89.7
88.8%
|
58.3
57.7%
|
89.1
168.1%
|
| Dengue Virus Serotype 4:30 days post-injection 3 |
94.2
93.3%
|
69.1
68.4%
|
93.3
176%
|
| Title | Percentage of Participants With Antibody Titers >=10 1/Dil Against At Least Any 1, 2, 3 or All 4 Dengue Virus Serotypes |
|---|---|
| Description | Percentage of participants with antibody titers >= 10 1/dil against each serotypes (1, 2, 3 and 4) of the dengue virus strains was assessed by PRNT. In this outcome measure, participants with antibody titers >= 10 1/dil against any 1 of the 4 serotypes or any 2 of the 4 serotypes or any 3 of the 4 serotypes or with all 4 serotypes were reported. |
| Time Frame | Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on FAS population. Here, 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | CYD Dengue Vaccine 5555 Formulation | CYD Dengue Vaccine 5553 Formulation | CYD Dengue Vaccine 4444 Formulation |
|---|---|---|---|
| Arm/Group Description | Participants received 3 doses of CYD dengue vaccine (5555 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Participants received 3 doses of CYD dengue vaccine (5553 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Participants received 3 doses of CYD dengue vaccine (4444 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. |
| Measure Participants | 101 | 101 | 53 |
| At least 1 positive serotype: Day 0 |
16.8
16.6%
|
20.8
20.6%
|
17.0
32.1%
|
| At least 1 positive serotype: Post-injection 1 |
96.0
95%
|
93.1
92.2%
|
98.1
185.1%
|
| At least 1 positive serotype: Post-injection 2 |
97.6
96.6%
|
97.6
96.6%
|
97.8
184.5%
|
| At least 1 positive serotype: Post-injection 3 |
100.0
99%
|
100.0
99%
|
100.0
188.7%
|
| At least 2 positive serotype: Day 0 |
3.0
3%
|
3.0
3%
|
3.8
7.2%
|
| At least 2 positive serotype: Post-injection 1 |
80.2
79.4%
|
74.3
73.6%
|
64.2
121.1%
|
| At least 2 positive serotype: Post-injection 2 |
90.2
89.3%
|
90.5
89.6%
|
82.6
155.8%
|
| At least 2 positive serotype: Post-injection 3 |
90.0
89.1%
|
95.1
94.2%
|
91.1
171.9%
|
| At least 3 positive serotype: Day 0 |
1.0
1%
|
2.0
2%
|
1.9
3.6%
|
| At least 3 positive serotype: Post-injection 1 |
50.5
50%
|
45.5
45%
|
41.5
78.3%
|
| At least 3 positive serotype: Post-injection 2 |
72.0
71.3%
|
79.8
79%
|
63.0
118.9%
|
| At least 3 positive serotype: Post-injection 3 |
82.9
82.1%
|
86.4
85.5%
|
73.3
138.3%
|
| All 4 positive serotype: Day 0 |
0.0
0%
|
2.0
2%
|
1.9
3.6%
|
| All 4 positive serotype: Post-injection 1 |
16.8
16.6%
|
19.8
19.6%
|
11.3
21.3%
|
| All 4 positive serotype: Post-injection 2 |
52.4
51.9%
|
47.6
47.1%
|
41.3
77.9%
|
| All 4 positive serotype: Post-injection 3 |
62.9
62.3%
|
59.3
58.7%
|
53.3
100.6%
|
| Title | Geometric Means of Titers of Antibodies Against Each Dengue Virus Serotype Strain |
|---|---|
| Description | Geometric mean titers against each dengue virus serotype (1, 2, 3 and 4) strain was measured by PRNT. |
| Time Frame | Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on FAS population. Here, 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | CYD Dengue Vaccine 5555 Formulation | CYD Dengue Vaccine 5553 Formulation | CYD Dengue Vaccine 4444 Formulation |
|---|---|---|---|
| Arm/Group Description | Participants received 3 doses of CYD dengue vaccine (5555 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Participants received 3 doses of CYD dengue vaccine (5553 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Participants received 3 doses of CYD dengue vaccine (4444 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. |
| Measure Participants | 101 | 101 | 53 |
| Dengue Virus Serotype 1: Day 0 |
5.04
|
5.57
|
5.23
|
| Dengue Virus Serotype 1:30 days post-injection 1 |
9.97
|
20.3
|
9.29
|
| Dengue Virus Serotype 1:30 days post-injection 2 |
24.1
|
45.4
|
19.2
|
| Dengue Virus Serotype 1:30 days post-injection 3 |
24.4
|
57.1
|
24.2
|
| Dengue Virus Serotype 2: Day 0 |
5.13
|
5.53
|
5.43
|
| Dengue Virus Serotype 2:30 days post-injection 1 |
16.7
|
39.9
|
13.1
|
| Dengue Virus Serotype 2:30 days post-injection 2 |
47.5
|
91.9
|
31.8
|
| Dengue Virus Serotype 2:30 days post-injection 3 |
54.8
|
102
|
46.5
|
| Dengue Virus Serotype 3: Day 0 |
6.60
|
6.85
|
6.25
|
| Dengue Virus Serotype 3:30 days post-injection 1 |
45.5
|
109
|
23.3
|
| Dengue Virus Serotype 3:30 days post-injection 2 |
64.5
|
117
|
40.4
|
| Dengue Virus Serotype 3:30 days post-injection 3 |
63.5
|
114
|
43.1
|
| Dengue Virus Serotype 4: Day 0 |
5.26
|
5.57
|
5.43
|
| Dengue Virus Serotype 4:30 days post-injection 1 |
438
|
12.1
|
643
|
| Dengue Virus Serotype 4:30 days post-injection 2 |
150
|
18.3
|
164
|
| Dengue Virus Serotype 4:30 days post-injection 3 |
133
|
25.9
|
134
|
| Title | Number of Participants With Solicited Injection Site Reactions After Any Vaccination |
|---|---|
| Description | Solicited injection site reactions: Pain, Erythema, and Swelling. Pain: Grade 1: Easily tolerated, Grade 2: Sufficiently discomforting to interfere with normal behavior or activities, Grade 3: Incapacitating, unable to perform usual activities. Erythema:- Grade 1: <2.5 cm, Grade 2: >=2.5 to <5 cm, Grade 3: >=5 cm. Swelling:- Grade 1: <2.5 cm, Grade 2: >=2.5 to <5 cm, Grade 3: >=5 cm. |
| Time Frame | 7 days after any injection 1, 2 or 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on Safety Analysis Set which included all participants included in the trial who had received at least 1 dose of study vaccine and had any available safety data. Here, 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | CYD Dengue Vaccine 5555 Formulation | CYD Dengue Vaccine 5553 Formulation | CYD Dengue Vaccine 4444 Formulation |
|---|---|---|---|
| Arm/Group Description | Participants received 3 doses of CYD dengue vaccine (5555 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Participants received 3 doses of CYD dengue vaccine (5553 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Participants received 3 doses of CYD dengue vaccine (4444 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. |
| Measure Participants | 101 | 101 | 53 |
| Pain |
50
49.5%
|
42
41.6%
|
15
28.3%
|
| Pain: Grade 1 |
46
45.5%
|
35
34.7%
|
15
28.3%
|
| Pain: Grade 2 |
3
3%
|
7
6.9%
|
0
0%
|
| Pain: Grade 3 |
1
1%
|
0
0%
|
0
0%
|
| Erythema |
26
25.7%
|
27
26.7%
|
8
15.1%
|
| Erythema: Grade 1 |
18
17.8%
|
19
18.8%
|
8
15.1%
|
| Erythema: Grade 2 |
7
6.9%
|
7
6.9%
|
0
0%
|
| Erythema: Grade 3 |
1
1%
|
1
1%
|
0
0%
|
| Swelling |
19
18.8%
|
14
13.9%
|
3
5.7%
|
| Swelling: Grade 1 |
15
14.9%
|
12
11.9%
|
3
5.7%
|
| Swelling: Grade 2 |
3
3%
|
2
2%
|
0
0%
|
| Swelling: Grade 3 |
1
1%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Solicited Systemic Reactions After Any Vaccination |
|---|---|
| Description | Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Fever: - Grade1: >=37.5°C to <=38.0°C (>=99.5°F to <=100.4°F), Grade 2: >38.0°C to <=39.0°C (>100.4°F to <= 102.2°F), Grade 3: >39.0°C (>102.2°F). Headache, malaise, myalgia and asthenia: Grade 1: noticeable but does not interfere with daily activities, Grade 2: interferes with daily activities, Grade 3: prevents daily activities. |
| Time Frame | 14 days after any injection 1, 2 or 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on safety analysis set. Here, 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | CYD Dengue Vaccine 5555 Formulation | CYD Dengue Vaccine 5553 Formulation | CYD Dengue Vaccine 4444 Formulation |
|---|---|---|---|
| Arm/Group Description | Participants received 3 doses of CYD dengue vaccine (5555 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Participants received 3 doses of CYD dengue vaccine (5553 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Participants received 3 doses of CYD dengue vaccine (4444 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. |
| Measure Participants | 101 | 101 | 53 |
| Fever |
14
13.9%
|
20
19.8%
|
6
11.3%
|
| Fever: Grade 1 |
11
10.9%
|
18
17.8%
|
3
5.7%
|
| Fever: Grade 2 |
2
2%
|
2
2%
|
3
5.7%
|
| Fever: Grade 3 |
1
1%
|
0
0%
|
0
0%
|
| Headache |
58
57.4%
|
59
58.4%
|
28
52.8%
|
| Headache: Grade 1 |
28
27.7%
|
38
37.6%
|
16
30.2%
|
| Headache: Grade 2 |
24
23.8%
|
18
17.8%
|
9
17%
|
| Headache: Grade 3 |
6
5.9%
|
3
3%
|
3
5.7%
|
| Malaise |
39
38.6%
|
43
42.6%
|
14
26.4%
|
| Malaise: Grade 1 |
16
15.8%
|
26
25.7%
|
9
17%
|
| Malaise: Grade 2 |
19
18.8%
|
12
11.9%
|
5
9.4%
|
| Malaise: Grade 3 |
4
4%
|
5
5%
|
0
0%
|
| Myalgia |
43
42.6%
|
49
48.5%
|
18
34%
|
| Myalgia: Grade 1 |
29
28.7%
|
30
29.7%
|
10
18.9%
|
| Myalgia: Grade 2 |
10
9.9%
|
17
16.8%
|
7
13.2%
|
| Myalgia: Grade 3 |
4
4%
|
2
2%
|
1
1.9%
|
| Asthenia |
29
28.7%
|
32
31.7%
|
12
22.6%
|
| Asthenia: Grade 1 |
18
17.8%
|
17
16.8%
|
9
17%
|
| Asthenia: Grade 2 |
8
7.9%
|
14
13.9%
|
3
5.7%
|
| Asthenia: Grade 3 |
3
3%
|
1
1%
|
0
0%
|
| Title | Number of Participants With Vaccine Viremia |
|---|---|
| Description | Vaccine viremia (level of vaccine virus in blood samples taken from participants) was measured by an assay yellow fever reverse transcriptase polymerase chain reaction which allowed the detection of vaccine viremia of any serotype (1, 2, 3 and 4). |
| Time Frame | 7 days post-injection 1 and 2, 14 days post-injection 1 and 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on Viremia Analysis Set which included all participants who received study vaccination and provided at least one blood sample for which vaccine viremia laboratory results were available. Here, 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | CYD Dengue Vaccine 5555 Formulation | CYD Dengue Vaccine 5553 Formulation | CYD Dengue Vaccine 4444 Formulation |
|---|---|---|---|
| Arm/Group Description | Participants received 3 doses of CYD dengue vaccine (5555 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Participants received 3 doses of CYD dengue vaccine (5553 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Participants received 3 doses of CYD dengue vaccine (4444 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. |
| Measure Participants | 26 | 26 | 26 |
| Vaccine viremia 7 days post-injection 1 |
0
0%
|
0
0%
|
0
0%
|
| Vaccine viremia 14 days post-injection 1 |
0
0%
|
0
0%
|
0
0%
|
| Vaccine viremia 7 days post-injection 2 |
0
0%
|
0
0%
|
0
0%
|
| Vaccine viremia 14 days post-injection 2 |
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | Adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each dose of CYD dengue vaccine or Placebo. Solicited Reaction (SR) data were collected within 7 and 14 days after each vaccination. Serious adverse event (SAE) data were collected throughout the study, up to 6 months after last vaccination (up to 18 months). | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Analysis was performed on Safety Analysis Set. | |||||
| Arm/Group Title | CYD Dengue Vaccine 5555 Formulation | CYD Dengue Vaccine 5553 Formulation | CYD Dengue Vaccine 4444 Formulation | |||
| Arm/Group Description | Participants received 3 doses of CYD dengue vaccine (5555 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Participants received 3 doses of CYD dengue vaccine (5553 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | Participants received 3 doses of CYD dengue vaccine (4444 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. | |||
All Cause Mortality |
||||||
| CYD Dengue Vaccine 5555 Formulation | CYD Dengue Vaccine 5553 Formulation | CYD Dengue Vaccine 4444 Formulation | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/101 (0%) | 0/101 (0%) | 0/53 (0%) | |||
Serious Adverse Events |
||||||
| CYD Dengue Vaccine 5555 Formulation | CYD Dengue Vaccine 5553 Formulation | CYD Dengue Vaccine 4444 Formulation | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/101 (3%) | 3/101 (3%) | 1/53 (1.9%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Benign Pancreatic Neoplasm | 1/101 (1%) | 1 | 0/101 (0%) | 0 | 0/53 (0%) | 0 |
| Breast Cancer | 1/101 (1%) | 1 | 0/101 (0%) | 0 | 0/53 (0%) | 0 |
| Nervous system disorders | ||||||
| Convulsion | 0/101 (0%) | 0 | 1/101 (1%) | 1 | 0/53 (0%) | 0 |
| Optic Neuritis | 1/101 (1%) | 1 | 0/101 (0%) | 0 | 0/53 (0%) | 0 |
| Pregnancy, puerperium and perinatal conditions | ||||||
| Abortion Spontaneous | 0/101 (0%) | 0 | 2/101 (2%) | 2 | 0/53 (0%) | 0 |
| Psychiatric disorders | ||||||
| Post-Traumatic Stress Disorder | 0/101 (0%) | 0 | 0/101 (0%) | 0 | 1/53 (1.9%) | 1 |
| Suicidal Ideation | 0/101 (0%) | 0 | 0/101 (0%) | 0 | 1/53 (1.9%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| CYD Dengue Vaccine 5555 Formulation | CYD Dengue Vaccine 5553 Formulation | CYD Dengue Vaccine 4444 Formulation | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 78/101 (77.2%) | 82/101 (81.2%) | 39/53 (73.6%) | |||
| General disorders | ||||||
| Asthenia | 29/101 (28.7%) | 38 | 32/101 (31.7%) | 41 | 12/53 (22.6%) | 14 |
| Injection Site Erythema | 26/101 (25.7%) | 36 | 27/101 (26.7%) | 34 | 8/53 (15.1%) | 11 |
| Injection Site Pain | 50/101 (49.5%) | 73 | 42/101 (41.6%) | 64 | 16/53 (30.2%) | 21 |
| Injection Site Swelling | 19/101 (18.8%) | 23 | 14/101 (13.9%) | 14 | 3/53 (5.7%) | 4 |
| Malaise | 39/101 (38.6%) | 63 | 43/101 (42.6%) | 57 | 14/53 (26.4%) | 17 |
| Pyrexia | 14/101 (13.9%) | 17 | 21/101 (20.8%) | 25 | 6/53 (11.3%) | 8 |
| Infections and infestations | ||||||
| Upper Respiratory Tract Infection | 6/101 (5.9%) | 6 | 7/101 (6.9%) | 7 | 2/53 (3.8%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||
| Myalgia | 43/101 (42.6%) | 68 | 50/101 (49.5%) | 72 | 18/53 (34%) | 21 |
| Nervous system disorders | ||||||
| Headache | 59/101 (58.4%) | 104 | 60/101 (59.4%) | 94 | 28/53 (52.8%) | 39 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable participant matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications.
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Sanofi Pasteur Inc. |
| Phone | |
| Contact-US@sanofi.com |
Responsible Party:
Sanofi
ClinicalTrials.gov Identifier:
NCT00617344
Other Study ID Numbers:
- CYD12
First Posted:
Feb 18, 2008
Last Update Posted:
Jun 11, 2019
Last Verified:
May 1, 2019