Study of Yellow Fever Vaccine Administered With Tetravalent Dengue Vaccine in Healthy Toddlers
Sponsor
Sanofi Pasteur, a Sanofi Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01436396
Collaborator
(none)
792
2
2
23.9
396
16.6
Study Details
Study Description
Brief Summary
The study was designed to evaluate whether the first CYD dengue vaccination can be administered concomitantly with Stamaril® yellow fever vaccine during the same day and visit, but at 2 different sites of administration.
Primary Objective:
- To demonstrate the non-inferiority of the immune response against Yellow Fever (YF) in flavivirus (FV) non-immune subjects at baseline receiving one dose of Stamaril vaccine administered concomitantly with the first dose of CYD dengue vaccine compared to participants receiving one dose of Stamaril vaccine concomitantly with placebo.
Secondary Objectives:
-
To assess the non-inferiority of YF immune response 28 days post-Stamaril vaccination based on seroconversion rates regardless of the FV status of participants at baseline.
-
To describe the YF immune response 28 days post-Stamaril vaccination in both groups.
-
To describe the antibody (Ab) response to each dengue virus serotype 28 days post CYD dengue vaccine (Visit [V] 05 and V07), following CYD dengue vaccine Dose 1 and Dose 2 from Group 2 versus following CYD dengue vaccine Dose 2 and Dose 3 for Group 1 (effect of YF vaccination).
-
To describe the safety of Stamaril vaccine administered concomitantly with the first dose of CYD dengue vaccine, or Stamaril administered concomitantly with placebo.
-
To describe the safety of CYD dengue vaccine after the first dose of CYD dengue vaccine administered concomitantly with Stamaril vaccine or CYD vaccine administered alone.
-
To describe the safety of the CYD dengue vaccine in all participants after each dose.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
All participants received a total of 9 injections during the study. Vaccine immunogenicity assessments for dengue neutralizing antibodies was performed in a randomized subset of participants. All participants were followed-up for safety during the study and for 6 months after the last CYD dengue vaccination.
Study Design
Study Type:
Interventional
Actual Enrollment
:
792 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
To ensure that objective safety data were obtained, the trial was designed using an observer-blind methodology since the products were visually different and may be recognized. For first trial vaccination (V01), the person who administered the injections knew which products were administered while either the participant or parent nor the Investigator in charge of safety evaluation knew which products were administered.
Primary Purpose:
Prevention
Official Title:
Immunogenicity and Safety of Yellow Fever Vaccine (Stamaril®) Administered Concomitantly With Tetravalent Dengue Vaccine in Healthy Toddlers at 12-13 Months of Age in Colombia and Peru
Actual Study Start Date
:
Sep 7, 2011
Actual Primary Completion Date
:
Sep 1, 2013
Actual Study Completion Date
:
Sep 2, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CYD Dengue Vaccine Group Participants received the Stamaril® and the CYD dengue vaccine (Injection 1) at enrolment (Month [M] 0) at age 12 to 13 months; measles, mumps and rubella vaccine, pneumococcal conjugated vaccine, hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP-IPV/Hib) vaccine at M7 (age 19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). |
Biological: Live, attenuated dengue serotype 1, 2, 3, and 4 virus
0.5 mL, subcutaneous at age 12, 18, and 24 months
Other Names:
Biological: Yellow fever vaccine
0.5 mL subcutaneous in the deltoid at age 12 to 13 months.
Other Names:
Biological: Measles, mumps, and rubella (MMR) vaccine
0.5 mL, subcutaneous at age 12 to 13 months.
Other Names:
Biological: Pneumococcal Conjugated Vaccine
0.5 mL, intramuscular at age 13 to 14 months
Biological: Hepatitis A Pediatric Vaccine
0.5 mL, intramuscular at age 13 to 14 months and 25 to 26 months
Biological: Diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae vaccine
0.5 mL, intramuscular at age 19 to 20 months
Other Names:
|
| Experimental: Placebo Group Participants received the Stamaril® vaccine and placebo matched to CYD vaccine (Injection 1) at enrolment (M0) (age 12 to 13 months); measles, mumps, and rubella vaccine, pneumococcal conjugate vaccine and hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); DTaP IPV/Hib vaccine at M7 (age19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). |
Biological: Live, attenuated dengue serotype 1, 2, 3, and 4 virus
0.5 mL, subcutaneous at age 18 to 19 and 24 to 25 months
Other Names:
Biological: Yellow Fever Vaccine
0.5 mL, subcutaneous at age 12 to 13 months
Other Names:
Biological: Placebo (NaCl)
0.5 mL, subcutaneous at age 12 to 13 months
Other Names:
Biological: Measles, mumps, and rubella vaccine
0.5 mL, subcutaneous at age 13 to 14 months
Other Names:
Biological: Pneumococcal Conjugated Vaccine
0.5 mL, intramuscular at age 13 to 14 months
Biological: Diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae vaccine
0.5 mL, intramuscular at age 19 to 20 months
Other Names:
Biological: Hepatitis A Pediatric Vaccine
0.5 mL, intramuscular at age 13 to 14 months and 25 to 26 months
|
Outcome Measures
Primary Outcome Measures
- Percentage of Flavi Virus (FV) Non-immune Participants With Seroconversion Against YF Antigen After Vaccination With Yellow Fever (YF) Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo [28 days Post-Injection 1]
Neutralizing antibodies against YF were assessed using a YF virus plaque reduction neutralization test (YF PRNT50) assay. Seroconversion was defined as YF antibodies >=10 (1/dilution [dil]) in flavivirus non-immune participants (defined as those with YF antibodies <10 [1/dil] for all serotypes (Serotype 1, 2, 3 and 4) with parental dengue virus strains and for YF virus).
Secondary Outcome Measures
- Percentage of All Participants With Seroconversion Against YF Antigen After Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo [28 days Post-Injection 1]
Neutralizing antibodies against YF were assessed using a YF virus plaque reduction neutralization test (YF PRNT50) assay. Seroconversion was defined as YF antibodies >= 10 (1/dil) in participants YF-seronegative at baseline or 4-fold increase from pre- to post-YF antibody titers in participants YF-seropositive at baseline.
- Geometric Mean Titers (GMTs) of YF Antibodies in All Participants Following Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo [Pre-Injection 1 and 28-days Post-Injection 1]
GMTs against YF were assessed using a YF virus plaque reduction neutralization test (YF PRNT50) assay.
- Geometric Mean Titer Ratios (GMTRs) of YF Antibodies in All Participants Following Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo [Pre-Injection 1 and 28- days Post-Injection 1]
GMTs ratios against YF were assessed using a YF virus plaque reduction neutralization test (YF PRNT50) assay.
- Percentage of All Participants With YF Antibody Titers of >=10 (1/Dil) Before and After Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo [Pre-Injection 1 and 28-days Post-Injection 1]
Neutralizing antibodies against YF were assessed using a YF virus plaque reduction neutralization test (YF PRNT50) assay. Seroconversion was defined as YF antibodies >=10 (1/dil) regardless of the flavivirus status of participants at baseline.
- GMTs of Dengue Virus Antibodies Following Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo [Pre-Injection 1 and 28-days Post-Injections 2 and 3]
GMTs against each serotype (Serotype 1, 2, 3 and 4) with the parental dengue virus strains were assessed using a dengue plaque reduction neutralization test (PRNT) assay.
- GMTRs of Dengue Virus Antibodies Following Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo [Pre-Injection 1 and 28-days Post-Injections 2 and 3]
GMTRs against each serotype (Serotype 1, 2, 3 and 4) with the parental dengue virus strains were assessed using a dengue PRNT assay.
- Percentage of Participants With Antibody Titer >= 10 (1/Dil) Against Each Serotype With Parental Dengue Virus Strains After Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo [Pre-Injection 1 and 28-days Post-Injections 2 and 3]
Neutralizing antibodies against each serotype (Serotype 1, 2, 3 and 4) with the parental dengue virus strains were assessed using a dengue PRNT assay. Seroconversion was defined as antibody titers >= 10 (1/dil) against each serotype (Serotype 1, 2, 3 and 4) with the parental dengue virus strains.
- Percentage of Participants With Antibody Titer >= 10 (1/Dil) Against at Least 1, 2, 3, or 4 Serotypes With Parental Dengue Virus Strains After YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo [Pre-Injection 1 and 28 days Post-Injections 2 and 3]
Neutralizing antibodies against at least 1, 2, 3, or 4 serotypes (Serotype 1, 2, 3 and 4) with the parental dengue virus strains were assessed using a dengue PRNT assay.
- GMTs of Dengue Virus Antibodies of FV Immune Participants Following Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo [Pre-Injection 1 and 28 days Post-Injections 2 and 3]
GMTs against each serotype (Serotype 1, 2, 3 and 4) with the parental dengue virus strains were assessed using a dengue PRNT assay. FV immune participants at baseline were defined as those participants with >= 10 (1/dil) for at least 1 serotype with the parental dengue virus strain or for YF virus.
- GMTs of Dengue Virus Antibodies of FV-Non Immune (Naïve) Participants Following Vaccination With YF Vaccine Non Immune (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo [Pre-Injection 1 and 28 days Post-Injections 2 and 3]
GMTs against each serotype (Serotype 1, 2, 3 and 4) with the parental dengue virus strains were assessed using a dengue PRNT assay. FV-non-immune participants at baseline were defined as those participants with <10 (1/dil) for all serotypes (Serotype 1, 2, 3 and 4) with parental dengue virus strains and for YF virus.
- Percentage of FV-immune Participants With Antibody Titer >= 10 (1/Dil) Against Each Serotype With Parental Dengue Virus Strains After YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo [Pre-Injection 1 and 28 days Post-Injections 2 and 3]
Neutralizing antibodies against each serotype (Serotype 1, 2, 3 and 4) with the parental dengue virus strains were assessed using a dengue PRNT assay. FV-immune participants at baseline were defined as those participants with >= 10 (1/dil) for at least 1 serotype (Serotype 1, 2, 3 and 4) with the parental dengue virus strain or for YF virus.
- Percentage of FV Non-immune (Naïve) Participants With Antibody Titer >= 10 (1/Dil) Against Each Serotype With the Parental Dengue Virus Strains After YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo [Pre-Injection 1 and 28 days Post-Injections 2 and 3]
Neutralizing antibodies against each serotype (Serotype 1, 2, 3 and 4) with the parental dengue virus strains were assessed using a dengue PRNT assay. FV non-immune participants at baseline were defined as those participants with <10 (1/dil) for all serotypes (Serotype 1, 2, 3 and 4) with parental dengue virus strains and for YF virus.
- Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following Any and Each Injection With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo [Day 0 up to 14 days post any Inj., Post Inj. 1, Post Inj. 2 and Post Inj. 3]
Solicited injection site reactions: Tenderness, Erythema, and Swelling. Solicited systemic reactions: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost and Irritability. Grade 3 Solicited injection site reactions: Tenderness: cries when injected limb is moved or the movement of the injected limb is reduced; Erythema and Swelling: >=50 millimeter (mm). Grade 3 Solicited systemic reactions: Fever: >39.5°celsius; Vomiting: >= episodes per 24 hours or requiring parenteral hydration; Crying abnormal: >3 hours; Drowsiness: sleeping most of the time or difficult to wake up; Appetite lost: refuses >=3 feeds/meals or refuses most feeds/meals; Irritability: inconsolable. Solicited Injection site reaction were reported separately for Stamaril®, CYD and placebo vaccine.
Eligibility Criteria
Criteria
Ages Eligible for Study:
12 Months
to 13 Months
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
Aged 12 to 13 months on the day of inclusion.
-
Born at full term of pregnancy (>=37 weeks) and with a birth weight >=2.5 kg as reported by the parent/legally acceptable representative.
-
Participant in good health, based on medical history and physical examination.
-
Participant had completed his/her vaccination schedule according to the official immunization calendar of Colombia and/or Peru, respectively.
-
Informed consent form had been signed and dated by the parent(s) or other legally acceptable representative (and by 2 independent witnesses if required by local regulations).
-
Participant and parent/legally acceptable representative/tutor able to attend all scheduled visits and to comply with all trial procedures.
Exclusion Criteria:
-
Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the first trial vaccination.
-
Planned participation in another clinical trial during the present trial period.
-
Planned receipt of any vaccine in the 4 weeks following first trial vaccination.
-
Previous vaccination against YF, hepatitis A, or measles, mumps and rubella.
-
Receipt of blood or blood-derived products in the past 3 months which might interfere with assessment of the immune response.
-
Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 weeks or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
-
Personal known seropositivity for human immunodeficiency virus (HIV) as reported by the parent/legally acceptable representative.
-
History of previous maternal vaccination against YF as reported by the parent/legally acceptable representative.
-
Personal history of YF or dengue infection/disease as reported by the parent/legally acceptable representative.
-
Known systemic hypersensitivity to any of the vaccine components of the vaccines that were used in the trial, or history of a life-threatening reaction to the vaccines used in the trial or to vaccines containing any of the same substances.
-
History of contraindication to receipt of vaccines containing components of Stamaril® (yellow fever vaccine), measles, mumps and rubella vaccine, hepatitis A vaccine, pneumococcal conjugated vaccine or of diphtheria (D) toxoid, tetanus (T) toxoid, pertussis toxoid (PT), filamentous hemagglutinin (FHA), polyribosylribitol phosphate (PRP) and polio or other diphtheria, tetanus and pertussis vaccine (e.g., DTwP).
-
Thrombocytopenia, as reported by the parent/legally acceptable representative.
-
Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular (IM) vaccination.
-
History of central nervous system disorder or disease, including seizures.
-
Personal history of thymic pathology (e.g., thymoma), and/or thymectomy.
-
Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion.
-
Identified as a child (adopted or natural) of the Investigator or of employees of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cali | Colombia | |||
| 2 | Lima | Peru |
Sponsors and Collaborators
- Sanofi Pasteur, a Sanofi Company
Investigators
- Study Director: Medical Director, Sanofi Pasteur Inc.
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Sanofi Pasteur, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT01436396
Other Study ID Numbers:
- CYD29
- U1111-1116-4913
- 2014-001714-26
First Posted:
Sep 19, 2011
Last Update Posted:
Mar 25, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Sanofi Pasteur, a Sanofi Company
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Study participants were enrolled from 07 September 2011 to 08 March 2012 at 2 clinical sites (1 in Colombia and 1 in Peru). |
|---|---|
| Pre-assignment Detail | A total of 792 participants who met all of the inclusion criteria and none of the exclusion criteria were enrolled and randomized; 787 participants were vaccinated. |
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants received the Stamaril® and the CYD dengue vaccine (Injection [Inj.] 1) at enrolment (M0) at age 12 to 13 months; measles, mumps and rubella vaccine, pneumococcal conjugated vaccine, hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP IPV/Hib) vaccine at M7 (age 19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). | Participants received the Stamaril® vaccine and placebo matched to CYD vaccine (Injection 1) at enrolment (M0) (age 12 to 13 months); measles, mumps, and rubella vaccine, pneumococcal conjugate vaccine and hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); DTaP IPV/Hib vaccine at M7 (age19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). |
| Period Title: Overall Study | ||
| STARTED | 396 | 396 |
| Vaccinated | 394 | 393 |
| COMPLETED | 364 | 354 |
| NOT COMPLETED | 32 | 42 |
Baseline Characteristics
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group | Total |
|---|---|---|---|
| Arm/Group Description | Participants received the Stamaril® and the CYD dengue vaccine (Injection 1) at enrolment (M0) at age 12 to 13 months; measles, mumps and rubella vaccine, pneumococcal conjugated vaccine, hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP IPV/Hib) vaccine at M7 (age 19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). | Participants received the Stamaril® vaccine and placebo matched to CYD vaccine (Injection 1) at enrolment (M0) (age 12 to 13 months); measles, mumps, and rubella vaccine, pneumococcal conjugate vaccine and hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); DTaP IPV/Hib vaccine at M7 (age19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). | Total of all reporting groups |
| Overall Participants | 394 | 393 | 787 |
| Age (Count of Participants) | |||
| <=18 years |
394
100%
|
393
100%
|
787
100%
|
| Between 18 and 65 years |
0
0%
|
0
0%
|
0
0%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Age (Months) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Months] |
12.2
(0.25)
|
12.2
(0.25)
|
12.2
(0.25)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
198
50.3%
|
203
51.7%
|
401
51%
|
| Male |
196
49.7%
|
190
48.3%
|
386
49%
|
Outcome Measures
| Title | Percentage of Flavi Virus (FV) Non-immune Participants With Seroconversion Against YF Antigen After Vaccination With Yellow Fever (YF) Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | Neutralizing antibodies against YF were assessed using a YF virus plaque reduction neutralization test (YF PRNT50) assay. Seroconversion was defined as YF antibodies >=10 (1/dilution [dil]) in flavivirus non-immune participants (defined as those with YF antibodies <10 [1/dil] for all serotypes (Serotype 1, 2, 3 and 4) with parental dengue virus strains and for YF virus). |
| Time Frame | 28 days Post-Injection 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on Per-Protocol analysis set which included all participants who had no protocol deviations. Per-Protocol analysis set was defined for the Stamaril® vaccine immune response. |
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants received the Stamaril® and the CYD dengue vaccine (Injection 1) at enrolment (M0) at age 12 to 13 months; measles, mumps and rubella vaccine, pneumococcal conjugated vaccine, hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP IPV/Hib) vaccine at M7 (age 19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). | Participants received the Stamaril® vaccine and placebo matched to CYD vaccine (Injection 1) at enrolment (M0) (age 12 to 13 months); measles, mumps, and rubella vaccine, pneumococcal conjugate vaccine and hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); DTaP IPV/Hib vaccine at M7 (age19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). |
| Measure Participants | 296 | 299 |
| Number [Percentage of participants] |
100.0
25.4%
|
99.7
25.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CYD Dengue Vaccine Group, Placebo Group |
|---|---|---|
| Comments | Non-inferiority of YF seroconversion rate was assessed 28 days post-Stamaril®/CYD dengue vaccine (CYD Dengue Vaccine Group) or post-Stamaril®/placebo (Placebo Group). | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | The non-inferiority was demonstrated if the lower limit of the 95% Confidence Interval (CI) was greater than -10. The difference in percentage of seroconversion rates between group 1 and 2 was based on the Wilson score (without continuity adjustment) 95% two-sided CI. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage |
| Estimated Value | 0.334 | |
| Confidence Interval |
(2-Sided) 95% -0.976 to 1.87 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of All Participants With Seroconversion Against YF Antigen After Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | Neutralizing antibodies against YF were assessed using a YF virus plaque reduction neutralization test (YF PRNT50) assay. Seroconversion was defined as YF antibodies >= 10 (1/dil) in participants YF-seronegative at baseline or 4-fold increase from pre- to post-YF antibody titers in participants YF-seropositive at baseline. |
| Time Frame | 28 days Post-Injection 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis performed on Full analysis set included participants who received at least co-administration of Stamaril® vaccine with either 1st dose of CYD dengue vaccine or placebo, had blood sample post-Stamaril® vaccination drawn and a valid test result. Here, 'overall number of participants analyzed'=participants evaluable for this outcome measure. |
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants received the Stamaril® and the CYD dengue vaccine (Injection 1) at enrolment (M0) at age 12 to 13 months; measles, mumps and rubella vaccine, pneumococcal conjugated vaccine, hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP IPV/Hib) vaccine at M7 (age 19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). | Participants received the Stamaril® vaccine and placebo matched to CYD vaccine (Injection 1) at enrolment (M0) (age 12 to 13 months); measles, mumps, and rubella vaccine, pneumococcal conjugate vaccine and hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); DTaP IPV/Hib vaccine at M7 (age19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). |
| Measure Participants | 378 | 376 |
| Number [Percentage of participants] |
98.7
25.1%
|
99.7
25.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CYD Dengue Vaccine Group, Placebo Group |
|---|---|---|
| Comments | Non-inferiority of YF seroconversion rate was assessed 28 days post-Stamaril®/CYD dengue vaccine (CYD Dengue Vaccine Group) or post-Stamaril®/placebo (Placebo Group). | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | The non-inferiority was demonstrated if the lower limit of the 95% CI is greater than -10. The difference in percentage of seroconversion rates between group 1 and 2 was based on the Wilson score (without continuity adjustment) 95% two-sided CI. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage |
| Estimated Value | -1.06 | |
| Confidence Interval |
(2-Sided) 95% -2.81 to 0.383 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Geometric Mean Titers (GMTs) of YF Antibodies in All Participants Following Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | GMTs against YF were assessed using a YF virus plaque reduction neutralization test (YF PRNT50) assay. |
| Time Frame | Pre-Injection 1 and 28-days Post-Injection 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on Full analysis set. Here, 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants received the Stamaril® and the CYD dengue vaccine (Injection 1) at enrolment (M0) at age 12 to 13 months; measles, mumps and rubella vaccine, pneumococcal conjugated vaccine, hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP IPV/Hib) vaccine at M7 (age 19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). | Participants received the Stamaril® vaccine and placebo matched to CYD vaccine (Injection 1) at enrolment (M0) (age 12 to 13 months); measles, mumps, and rubella vaccine, pneumococcal conjugate vaccine and hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); DTaP IPV/Hib vaccine at M7 (age19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). |
| Measure Participants | 381 | 377 |
| Pre-Injection 1 |
5.64
|
5.67
|
| Post-Injection 1 |
369
|
423
|
| Title | Geometric Mean Titer Ratios (GMTRs) of YF Antibodies in All Participants Following Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | GMTs ratios against YF were assessed using a YF virus plaque reduction neutralization test (YF PRNT50) assay. |
| Time Frame | Pre-Injection 1 and 28- days Post-Injection 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on Full analysis set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure." |
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants received the Stamaril® and the CYD dengue vaccine (Injection 1) at enrolment (M0) at age 12 to 13 months; measles, mumps and rubella vaccine, pneumococcal conjugated vaccine, hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP IPV/Hib) vaccine at M7 (age 19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). | Participants received the Stamaril® vaccine and placebo matched to CYD vaccine (Injection 1) at enrolment (M0) (age 12 to 13 months); measles, mumps, and rubella vaccine, pneumococcal conjugate vaccine and hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); DTaP IPV/Hib vaccine at M7 (age19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). |
| Measure Participants | 378 | 376 |
| Geometric Mean (95% Confidence Interval) [Ratio] |
35.1
|
39.8
|
| Title | Percentage of All Participants With YF Antibody Titers of >=10 (1/Dil) Before and After Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | Neutralizing antibodies against YF were assessed using a YF virus plaque reduction neutralization test (YF PRNT50) assay. Seroconversion was defined as YF antibodies >=10 (1/dil) regardless of the flavivirus status of participants at baseline. |
| Time Frame | Pre-Injection 1 and 28-days Post-Injection 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on Full analysis set. Here, 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants received the Stamaril® and the CYD dengue vaccine (Injection 1) at enrolment (M0) at age 12 to 13 months; measles, mumps and rubella vaccine, pneumococcal conjugated vaccine, hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP IPV/Hib) vaccine at M7 (age 19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). | Participants received the Stamaril® vaccine and placebo matched to CYD vaccine (Injection 1) at enrolment (M0) (age 12 to 13 months); measles, mumps, and rubella vaccine, pneumococcal conjugate vaccine and hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); DTaP IPV/Hib vaccine at M7 (age19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). |
| Measure Participants | 381 | 377 |
| Pre-Injection 1 |
9.0
2.3%
|
9.0
2.3%
|
| Post-Injection 1 |
99.5
25.3%
|
99.7
25.4%
|
| Title | GMTs of Dengue Virus Antibodies Following Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | GMTs against each serotype (Serotype 1, 2, 3 and 4) with the parental dengue virus strains were assessed using a dengue plaque reduction neutralization test (PRNT) assay. |
| Time Frame | Pre-Injection 1 and 28-days Post-Injections 2 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis performed on Full analysis set for dengue immunogenicity which included participants who received at least 1dose of CYD dengue vaccine/placebo, had at least 1 blood sample withdrawn and valid post vaccination test results for at least 1 dengue serotype. Here,'number analyzed' =participants with available data for each specified category. |
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants received the Stamaril® and the CYD dengue vaccine (Injection 1) at enrolment (M0) at age 12 to 13 months; measles, mumps and rubella vaccine, pneumococcal conjugated vaccine, hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP IPV/Hib) vaccine at M7 (age 19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). | Participants received the Stamaril® vaccine and placebo matched to CYD vaccine (Injection 1) at enrolment (M0) (age 12 to 13 months); measles, mumps, and rubella vaccine, pneumococcal conjugate vaccine and hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); DTaP IPV/Hib vaccine at M7 (age19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). |
| Measure Participants | 113 | 113 |
| Serotype 1; Pre-Injection 1 |
5.08
|
5.00
|
| Serotype 1; Post-Injection 2 |
47.3
|
11.8
|
| Serotype 1; Post-Injection 3 |
89.0
|
61.3
|
| Serotype 2; Pre-Injection 1 |
5.10
|
5.00
|
| Serotype 2; Post-Injection 2 |
95.5
|
41.1
|
| Serotype 2; Post-Injection 3 |
173
|
150
|
| Serotype 3; Pre-Injection 1 |
5.05
|
5.18
|
| Serotype 3; Post-Injection 2 |
118
|
43.4
|
| Serotype 3; Post-Injection 3 |
181
|
155
|
| Serotype 4; Pre-Injection 1 |
5.00
|
5.05
|
| Serotype 4; Post-Injection 2 |
68.1
|
29.8
|
| Serotype 4; Post-Injection 3 |
74.0
|
74.6
|
| Title | GMTRs of Dengue Virus Antibodies Following Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | GMTRs against each serotype (Serotype 1, 2, 3 and 4) with the parental dengue virus strains were assessed using a dengue PRNT assay. |
| Time Frame | Pre-Injection 1 and 28-days Post-Injections 2 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on Full analysis set for dengue immunogenicity. Here, 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants received the Stamaril® and the CYD dengue vaccine (Injection 1) at enrolment (M0) at age 12 to 13 months; measles, mumps and rubella vaccine, pneumococcal conjugated vaccine, hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP IPV/Hib) vaccine at M7 (age 19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). | Participants received the Stamaril® vaccine and placebo matched to CYD vaccine (Injection 1) at enrolment (M0) (age 12 to 13 months); measles, mumps, and rubella vaccine, pneumococcal conjugate vaccine and hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); DTaP IPV/Hib vaccine at M7 (age19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). |
| Measure Participants | 113 | 113 |
| Serotype 1; Post-Inj.2/Pre-Inj. 1 |
4.78
|
1.15
|
| Serotype 1; Post-Inj.3/Pre-Inj. 1 |
8.82
|
6.14
|
| Serotype 2; Post-Inj.2/Pre-Inj. 1 |
9.55
|
3.86
|
| Serotype 2; Post-Inj.3/Pre-Inj. 1 |
16.7
|
15.2
|
| Serotype 3; Post-Inj.2/Pre-Inj. 1 |
11.6
|
4.16
|
| Serotype 3; Post-Inj.3/Pre-Inj. 1 |
18.0
|
15.4
|
| Serotype 4; Post-Inj.2/Pre-Inj. 1 |
6.82
|
2.89
|
| Serotype 4; Post-Inj.3/Pre-Inj. 1 |
7.26
|
7.44
|
| Title | Percentage of Participants With Antibody Titer >= 10 (1/Dil) Against Each Serotype With Parental Dengue Virus Strains After Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | Neutralizing antibodies against each serotype (Serotype 1, 2, 3 and 4) with the parental dengue virus strains were assessed using a dengue PRNT assay. Seroconversion was defined as antibody titers >= 10 (1/dil) against each serotype (Serotype 1, 2, 3 and 4) with the parental dengue virus strains. |
| Time Frame | Pre-Injection 1 and 28-days Post-Injections 2 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed Full analysis set for dengue immunogenicity. Here, 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants received the Stamaril® and the CYD dengue vaccine (Injection 1) at enrolment (M0) at age 12 to 13 months; measles, mumps and rubella vaccine, pneumococcal conjugated vaccine, hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP IPV/Hib) vaccine at M7 (age 19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). | Participants received the Stamaril® vaccine and placebo matched to CYD vaccine (Injection 1) at enrolment (M0) (age 12 to 13 months); measles, mumps, and rubella vaccine, pneumococcal conjugate vaccine and hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); DTaP IPV/Hib vaccine at M7 (age19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). |
| Measure Participants | 113 | 113 |
| Serotype 1; Pre-Injection 1 |
0.9
0.2%
|
0.0
0%
|
| Serotype 1; Post-Injection 2 |
92.0
23.4%
|
51.3
13.1%
|
| Serotype 1; Post-Injection 3 |
100.0
25.4%
|
97.2
24.7%
|
| Serotype 2; Pre-Injection 1 |
1.8
0.5%
|
0.0
0%
|
| Serotype 2; Post-Injection 2 |
97.3
24.7%
|
86.7
22.1%
|
| Serotype 2; Post-Injection 3 |
100.0
25.4%
|
100.0
25.4%
|
| Serotype 3; Pre-Injection 1 |
0.9
0.2%
|
3.7
0.9%
|
| Serotype 3; Post-Injection 2 |
100.0
25.4%
|
90.3
23%
|
| Serotype 3; Post-Injection 3 |
100.0
25.4%
|
100.0
25.4%
|
| Serotype 4; Pre-Injection 1 |
0.0
0%
|
0.9
0.2%
|
| Serotype 4; Post-Injection 2 |
91.2
23.1%
|
68.1
17.3%
|
| Serotype 4; Post-Injection 3 |
97.3
24.7%
|
98.1
25%
|
| Title | Percentage of Participants With Antibody Titer >= 10 (1/Dil) Against at Least 1, 2, 3, or 4 Serotypes With Parental Dengue Virus Strains After YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | Neutralizing antibodies against at least 1, 2, 3, or 4 serotypes (Serotype 1, 2, 3 and 4) with the parental dengue virus strains were assessed using a dengue PRNT assay. |
| Time Frame | Pre-Injection 1 and 28 days Post-Injections 2 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed Full analysis set for dengue immunogenicity. Here, 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants received the Stamaril® and the CYD dengue vaccine (Injection 1) at enrolment (M0) at age 12 to 13 months; measles, mumps and rubella vaccine, pneumococcal conjugated vaccine, hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP IPV/Hib) vaccine at M7 (age 19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). | Participants received the Stamaril® vaccine and placebo matched to CYD vaccine (Injection 1) at enrolment (M0) (age 12 to 13 months); measles, mumps, and rubella vaccine, pneumococcal conjugate vaccine and hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); DTaP IPV/Hib vaccine at M7 (age19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). |
| Measure Participants | 113 | 113 |
| At least 1 serotype; Pre-Injection 1 |
3.6
0.9%
|
4.5
1.1%
|
| At least 1 serotype; Post-Injection 2 |
100.0
25.4%
|
93.8
23.9%
|
| At least 1 serotype; Post-Injection 3 |
100.0
25.4%
|
100.0
25.4%
|
| At least 2 serotypes; Pre-Injection 1 |
0.0
0%
|
0.0
0%
|
| At least 2 serotypes; Post-Injection 2 |
100.0
25.4%
|
87.6
22.3%
|
| At least 2 serotypes; Post-Injection 3 |
100.0
25.4%
|
100.0
25.4%
|
| At least 3 serotypes; Pre-Injection 1 |
0.0
0%
|
0.0
0%
|
| At least 3 serotypes; Post-Injection 2 |
94.7
24%
|
73.5
18.7%
|
| At least 3 serotypes; Post-Injection 3 |
100.0
25.4%
|
98.1
25%
|
| All 4 serotypes; Pre-Injection 1 |
0.0
0%
|
0.0
0%
|
| All 4 serotypes; Post-Injection 2 |
85.8
21.8%
|
41.6
10.6%
|
| All 4 serotypes; Post-Injection 3 |
97.3
24.7%
|
97.2
24.7%
|
| Title | GMTs of Dengue Virus Antibodies of FV Immune Participants Following Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | GMTs against each serotype (Serotype 1, 2, 3 and 4) with the parental dengue virus strains were assessed using a dengue PRNT assay. FV immune participants at baseline were defined as those participants with >= 10 (1/dil) for at least 1 serotype with the parental dengue virus strain or for YF virus. |
| Time Frame | Pre-Injection 1 and 28 days Post-Injections 2 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on Full analysis set for dengue immunogenicity. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants received the Stamaril® and the CYD dengue vaccine (Injection 1) at enrolment (M0) at age 12 to 13 months; measles, mumps and rubella vaccine, pneumococcal conjugated vaccine, hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP IPV/Hib) vaccine at M7 (age 19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). | Participants received the Stamaril® vaccine and placebo matched to CYD vaccine (Injection 1) at enrolment (M0) (age 12 to 13 months); measles, mumps, and rubella vaccine, pneumococcal conjugate vaccine and hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); DTaP IPV/Hib vaccine at M7 (age19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). |
| Measure Participants | 10 | 14 |
| Serotype 1; Pre-Injection 1 |
5.96
|
5.00
|
| Serotype 1; Post-Injection 2 |
52.5
|
17.0
|
| Serotype 1; Post-Injection 3 |
81.7
|
59.5
|
| Serotype 2; Pre-Injection 1 |
6.14
|
5.00
|
| Serotype 2; Post-Injection 2 |
72.4
|
74.3
|
| Serotype 2; Post-Injection 3 |
110
|
133
|
| Serotype 3; Pre-Injection 1 |
5.74
|
6.75
|
| Serotype 3; Post-Injection 2 |
102
|
95.8
|
| Serotype 3; Post-Injection 3 |
143
|
126
|
| Serotype 4; Pre-Injection 1 |
5.00
|
5.41
|
| Serotype 4; Post-Injection 2 |
87.1
|
109
|
| Serotype 4; Post-Injection 3 |
77.1
|
74.3
|
| Title | GMTs of Dengue Virus Antibodies of FV-Non Immune (Naïve) Participants Following Vaccination With YF Vaccine Non Immune (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | GMTs against each serotype (Serotype 1, 2, 3 and 4) with the parental dengue virus strains were assessed using a dengue PRNT assay. FV-non-immune participants at baseline were defined as those participants with <10 (1/dil) for all serotypes (Serotype 1, 2, 3 and 4) with parental dengue virus strains and for YF virus. |
| Time Frame | Pre-Injection 1 and 28 days Post-Injections 2 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on Full analysis set for dengue immunogenicity. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants received the Stamaril® and the CYD dengue vaccine (Injection 1) at enrolment (M0) at age 12 to 13 months; measles, mumps and rubella vaccine, pneumococcal conjugated vaccine, hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP IPV/Hib) vaccine at M7 (age 19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). | Participants received the Stamaril® vaccine and placebo matched to CYD vaccine (Injection 1) at enrolment (M0) (age 12 to 13 months); measles, mumps, and rubella vaccine, pneumococcal conjugate vaccine and hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); DTaP IPV/Hib vaccine at M7 (age19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). |
| Measure Participants | 94 | 90 |
| Serotype 1; Pre-Injection 1 |
5.00
|
5.00
|
| Serotype 1; Post-Injection 2 |
45.9
|
11.4
|
| Serotype 1; Post-Injection 3 |
86.6
|
61.8
|
| Serotype 2; Pre-Injection 1 |
5.00
|
5.00
|
| Serotype 2; Post-Injection 2 |
99.0
|
39.0
|
| Serotype 2; Post-Injection 3 |
174
|
157
|
| Serotype 3; Pre-Injection 1 |
5.00
|
5.00
|
| Serotype 3; Post-Injection 2 |
118
|
37.9
|
| Serotype 3; Post-Injection 3 |
184
|
160
|
| Serotype 4; Pre-Injection 1 |
5.00
|
5.00
|
| Serotype 4; Post-Injection 2 |
66.4
|
24.0
|
| Serotype 4; Post-Injection 3 |
73.0
|
72.2
|
| Title | Percentage of FV-immune Participants With Antibody Titer >= 10 (1/Dil) Against Each Serotype With Parental Dengue Virus Strains After YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | Neutralizing antibodies against each serotype (Serotype 1, 2, 3 and 4) with the parental dengue virus strains were assessed using a dengue PRNT assay. FV-immune participants at baseline were defined as those participants with >= 10 (1/dil) for at least 1 serotype (Serotype 1, 2, 3 and 4) with the parental dengue virus strain or for YF virus. |
| Time Frame | Pre-Injection 1 and 28 days Post-Injections 2 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on Full analysis set for dengue immunogenicity. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants received the Stamaril® and the CYD dengue vaccine (Injection 1) at enrolment (M0) at age 12 to 13 months; measles, mumps and rubella vaccine, pneumococcal conjugated vaccine, hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP IPV/Hib) vaccine at M7 (age 19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). | Participants received the Stamaril® vaccine and placebo matched to CYD vaccine (Injection 1) at enrolment (M0) (age 12 to 13 months); measles, mumps, and rubella vaccine, pneumococcal conjugate vaccine and hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); DTaP IPV/Hib vaccine at M7 (age19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). |
| Measure Participants | 10 | 14 |
| Serotype 1; Pre-Injection 1 |
10.0
2.5%
|
0.0
0%
|
| Serotype 1; Post-Injection 2 |
90.0
22.8%
|
57.1
14.5%
|
| Serotype 1; Post-Injection 3 |
100.0
25.4%
|
100.0
25.4%
|
| Serotype 2; Pre-Injection 1 |
20.0
5.1%
|
0.0
0%
|
| Serotype 2; Post-Injection 2 |
100.0
25.4%
|
92.9
23.6%
|
| Serotype 2; Post-Injection 3 |
100.0
25.4%
|
100.0
25.4%
|
| Serotype 3; Pre-Injection 1 |
12.5
3.2%
|
30.8
7.8%
|
| Serotype 3; Post-Injection 2 |
100.0
25.4%
|
100.0
25.4%
|
| Serotype 3; Post-Injection 3 |
100.0
25.4%
|
100.0
25.4%
|
| Serotype 4; Pre-Injection 1 |
0.0
0%
|
7.7
2%
|
| Serotype 4; Post-Injection 2 |
90.0
22.8%
|
92.9
23.6%
|
| Serotype 4; Post-Injection 3 |
88.9
22.6%
|
100.0
25.4%
|
| Title | Percentage of FV Non-immune (Naïve) Participants With Antibody Titer >= 10 (1/Dil) Against Each Serotype With the Parental Dengue Virus Strains After YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | Neutralizing antibodies against each serotype (Serotype 1, 2, 3 and 4) with the parental dengue virus strains were assessed using a dengue PRNT assay. FV non-immune participants at baseline were defined as those participants with <10 (1/dil) for all serotypes (Serotype 1, 2, 3 and 4) with parental dengue virus strains and for YF virus. |
| Time Frame | Pre-Injection 1 and 28 days Post-Injections 2 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on Full analysis set for dengue immunogenicity. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants received the Stamaril® and the CYD dengue vaccine (Injection 1) at enrolment (M0) at age 12 to 13 months; measles, mumps and rubella vaccine, pneumococcal conjugated vaccine, hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP IPV/Hib) vaccine at M7 (age 19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). | Participants received the Stamaril® vaccine and placebo matched to CYD vaccine (Injection 1) at enrolment (M0) (age 12 to 13 months); measles, mumps, and rubella vaccine, pneumococcal conjugate vaccine and hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); DTaP IPV/Hib vaccine at M7 (age19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). |
| Measure Participants | 94 | 90 |
| Serotype 1; Pre-Injection 1 |
0.0
0%
|
0.0
0%
|
| Serotype 1; Post-Injection 2 |
92.6
23.5%
|
51.1
13%
|
| Serotype 1; Post-Injection 3 |
100.0
25.4%
|
96.5
24.6%
|
| Serotype 2; Pre-Injection 1 |
0.0
0%
|
0.0
0%
|
| Serotype 2; Post-Injection 2 |
96.8
24.6%
|
86.7
22.1%
|
| Serotype 2; Post-Injection 3 |
100.0
25.4%
|
100.0
25.4%
|
| Serotype 3; Pre-Injection 1 |
0.0
0%
|
0.0
0%
|
| Serotype 3; Post-Injection 2 |
100.0
25.4%
|
87.8
22.3%
|
| Serotype 3; Post-Injection 3 |
100.0
25.4%
|
100.0
25.4%
|
| Serotype 4; Pre-Injection 1 |
0.0
0%
|
0.0
0%
|
| Serotype 4; Post-Injection 2 |
90.4
22.9%
|
63.3
16.1%
|
| Serotype 4; Post-Injection 3 |
97.8
24.8%
|
97.7
24.9%
|
| Title | Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following Any and Each Injection With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | Solicited injection site reactions: Tenderness, Erythema, and Swelling. Solicited systemic reactions: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost and Irritability. Grade 3 Solicited injection site reactions: Tenderness: cries when injected limb is moved or the movement of the injected limb is reduced; Erythema and Swelling: >=50 millimeter (mm). Grade 3 Solicited systemic reactions: Fever: >39.5°celsius; Vomiting: >= episodes per 24 hours or requiring parenteral hydration; Crying abnormal: >3 hours; Drowsiness: sleeping most of the time or difficult to wake up; Appetite lost: refuses >=3 feeds/meals or refuses most feeds/meals; Irritability: inconsolable. Solicited Injection site reaction were reported separately for Stamaril®, CYD and placebo vaccine. |
| Time Frame | Day 0 up to 14 days post any Inj., Post Inj. 1, Post Inj. 2 and Post Inj. 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. "0" in "number analyzed" field= none of the participants were evaluable since participants did not received CYD dengue vaccine as Injection 1 (Placebo group) or Placebo at any time point (CYD dengue vaccine group). |
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants received the Stamaril® and the CYD dengue vaccine (Injection 1) at enrolment (M0) at age 12 to 13 months; measles, mumps and rubella vaccine, pneumococcal conjugated vaccine, hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP IPV/Hib) vaccine at M7 (age 19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). | Participants received the Stamaril® vaccine and placebo matched to CYD vaccine (Injection 1) at enrolment (M0) (age 12 to 13 months); measles, mumps, and rubella vaccine, pneumococcal conjugate vaccine and hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); DTaP IPV/Hib vaccine at M7 (age19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). |
| Measure Participants | 394 | 393 |
| Inj. site Tenderness for Stamaril®; Post-Any Inj. |
25.4
6.4%
|
17.6
4.5%
|
| Grd 3 Inj. site Tenderness, Stamaril®;Post-Any Inj |
0.3
0.1%
|
0.3
0.1%
|
| Inj. site Tenderness for CYD dengue;Post-Any Inj. |
36.5
9.3%
|
28.9
7.4%
|
| Grd 3 Inj site Tenderness, CYDdengue;Post-Any Inj |
0.3
0.1%
|
0.0
0%
|
| Inj. site Tenderness for placebo; Post-Any Inj. |
19.7
5%
|
|
| Grd 3 Inj. site Tenderness, placebo;Post-Any Inj. |
0.3
0.1%
|
|
| Inj. site Erythema for Stamaril®; Post-Any Inj. |
8.3
2.1%
|
9.8
2.5%
|
| Grd 3 Inj. site Erythema, Stamaril®;Post-Any Inj. |
0.0
0%
|
0.0
0%
|
| Inj. site Erythema for CYD dengue;Post-Any Inj. |
12.7
3.2%
|
8.8
2.2%
|
| Grd 3 Inj. site Erythema, CYD dengue;Post-Any Inj |
0.0
0%
|
0.0
0%
|
| Inj. site Erythema for placebo; Post-Any Inj. |
10.9
2.8%
|
|
| Grd 3 Inj. site Erythema for placebo; Post-Any Inj |
0.0
0%
|
|
| Inj. site Swelling for Stamaril®; Post-Any Inj. |
4.7
1.2%
|
4.4
1.1%
|
| Grd 3 Inj. site Swelling, Stamaril®; Post-Any Inj. |
0.0
0%
|
0.0
0%
|
| Inj. site Swelling for CYD dengue; Post-Any Inj. |
7.5
1.9%
|
6.1
1.6%
|
| Grd 3 Inj. site Swelling, CYD dengue; Post-Any Inj |
0.0
0%
|
0.0
0%
|
| Inj. site Swelling for placebo; Post-Any inj. |
4.9
1.2%
|
|
| Grd 3 Inj. site Swelling for placebo; Post-Any Inj |
0.0
0%
|
|
| Inj. site Tenderness for Stamaril®; Post-Inj. 1 |
25.4
6.4%
|
17.6
4.5%
|
| Grd 3 Inj. site Tenderness, Stamaril®; Post-Inj. 1 |
0.3
0.1%
|
0.3
0.1%
|
| Inj. site Tenderness for CYD dengue; Post-Inj. 1 |
24.9
6.3%
|
|
| Grd 3 Inj. site Tenderness, CYD dengue; Post-Inj 1 |
0.0
0%
|
|
| Inj. site Tenderness for placebo; Post-Inj. 1 |
19.7
5%
|
|
| Grd 3 Inj. site Tenderness, placebo; Post-Inj. 1 |
0.3
0.1%
|
|
| Inj. site Erythema for Stamaril®; Post-Inj. 1 |
8.3
2.1%
|
9.8
2.5%
|
| Grd 3 Inj.site Erythema for Stamaril®; Post-Inj. 1 |
0.0
0%
|
0.0
0%
|
| Inj. site Erythema for CYD dengue; Post-Inj. 1 |
8.8
2.2%
|
|
| Grd 3 Inj. site Erythema, CYD dengue; Post-Inj. 1 |
0.0
0%
|
|
| Inj. site Erythema for placebo; Post-Inj. 1 |
10.9
2.8%
|
|
| Grd 3 Inj. site Erythema for placebo; Post-Inj. 1 |
0.0
0%
|
|
| Inj. site Swelling for Stamaril®; Post-Inj. 1 |
4.7
1.2%
|
4.4
1.1%
|
| Grd 3 Inj.site Swelling for Stamaril®; Post-Inj. 1 |
0.0
0%
|
0.0
0%
|
| Inj. site Swelling for CYD dengue; Post-Inj. 1 |
4.7
1.2%
|
|
| Grd 3 Inj. site Swelling, CYD dengue; Post-Inj. 1 |
0.0
0%
|
|
| Inj. site Swelling for placebo; Post-Inj. 1 |
4.9
1.2%
|
|
| Grd 3 Inj. site Swelling for placebo; Post-Inj. 1 |
0.0
0%
|
|
| Inj. site Tenderness for CYD dengue; Post-Inj. 2 |
17.0
4.3%
|
20.4
5.2%
|
| Grd 3 Inj. site Tenderness, CYD dengue; Post-Inj 2 |
0.0
0%
|
0.0
0%
|
| Inj. site Erythema for CYD dengue; Post-Inj. 2 |
5.1
1.3%
|
8.0
2%
|
| Grd 3 Inj. site Erythema, CYD dengue; Post-Inj. 2 |
0.0
0%
|
0.0
0%
|
| Inj. site Swelling for CYD dengue; Post-Inj. 2 |
2.7
0.7%
|
4.7
1.2%
|
| Grd 3 Inj. site Swelling, CYD dengue; Post-Inj. 2 |
0.0
0%
|
0.0
0%
|
| Inj. site Tenderness for CYD dengue; Post-Inj. 3 |
14.6
3.7%
|
16.3
4.1%
|
| Grd 3 Inj. site Tenderness, CYD dengue; Post-Inj 3 |
0.3
0.1%
|
0.0
0%
|
| Inj. site Erythema for CYD dengue; Post-Inj. 3 |
3.6
0.9%
|
4.2
1.1%
|
| Grd 3 Inj. site Erythema, CYD dengue; Post-Inj. 3 |
0.0
0%
|
0.0
0%
|
| Inj. site Swelling for CYD dengue; Post-Inj. 3 |
1.6
0.4%
|
2.8
0.7%
|
| Grd 3 Inj. site Swelling, CYD dengue; Post-Inj. 3 |
0.0
0%
|
0.0
0%
|
| Fever; Post-Any Injection |
48.1
12.2%
|
40.3
10.3%
|
| Grade 3 Fever; Post-Any Injection |
1.3
0.3%
|
0.8
0.2%
|
| Vomiting; Post-Any Injection |
30.6
7.8%
|
27.2
6.9%
|
| Grade 3 Vomiting; Post-Any Injection |
1.3
0.3%
|
2.1
0.5%
|
| Crying abnormal; Post-Any Injection |
47.2
12%
|
44.0
11.2%
|
| Grade 3 Crying abnormal; Post-Any Injection |
0.5
0.1%
|
1.3
0.3%
|
| Drowsiness; Post-Any Injection |
36.3
9.2%
|
33.9
8.6%
|
| Grade 3 Drowsiness; Post-Any Injection |
0.5
0.1%
|
0.0
0%
|
| Appetite lost; Post-Any Injection |
54.7
13.9%
|
50.0
12.7%
|
| Grade 3 Appetite lost; Post-Any Injection |
4.7
1.2%
|
3.6
0.9%
|
| Irritability; Post-Any Injection |
46.4
11.8%
|
46.4
11.8%
|
| Grade 3 Irritability; Post-Any Injection |
1.6
0.4%
|
1.6
0.4%
|
| Fever; Post-Injection 1 |
26.7
6.8%
|
16.5
4.2%
|
| Grade 3 Fever; Post-Injection 1 |
1.1
0.3%
|
0.3
0.1%
|
| Vomiting; Post-Injection 1 |
16.1
4.1%
|
17.1
4.4%
|
| Grade 3 Vomiting; Post-Injection 1 |
0.5
0.1%
|
1.0
0.3%
|
| Crying abnormal; Post-Injection 1 |
32.9
8.4%
|
32.1
8.2%
|
| Grade 3 Crying abnormal; Post-Injection 1 |
0.5
0.1%
|
1.3
0.3%
|
| Drowsiness; Post-Injection 1 |
24.4
6.2%
|
22.0
5.6%
|
| Grade 3 Drowsiness; Post-Injection 1 |
0.5
0.1%
|
0.0
0%
|
| Appetite lost; Post-Injection 1 |
39.6
10.1%
|
33.7
8.6%
|
| Grade 3 Appetite lost; Post-Injection 1 |
4.4
1.1%
|
3.1
0.8%
|
| Irritability; Post-Injection 1 |
38.6
9.8%
|
34.7
8.8%
|
| Grade 3 Irritability; Post-Injection 1 |
1.6
0.4%
|
1.3
0.3%
|
| Fever; Post-Injection 2 |
21.2
5.4%
|
22.2
5.6%
|
| Grade 3 Fever; Post-Injection 2 |
0.0
0%
|
0.3
0.1%
|
| Vomiting; Post-Injection 2 |
12.4
3.1%
|
8.8
2.2%
|
| Grade 3 Vomiting; Post-Injection 2 |
0.5
0.1%
|
0.6
0.2%
|
| Crying abnormal; Post-Injection 2 |
19.7
5%
|
21.8
5.5%
|
| Grade 3 Crying abnormal; Post-Injection 2 |
0.0
0%
|
0.0
0%
|
| Drowsiness; Post-Injection 2 |
12.7
3.2%
|
16.5
4.2%
|
| Grade 3 Drowsiness; Post-Injection 2 |
0.0
0%
|
0.0
0%
|
| Appetite lost; Post-Injection 2 |
27.0
6.9%
|
23.1
5.9%
|
| Grade 3 Appetite lost; Post-Injection 2 |
0.3
0.1%
|
0.3
0.1%
|
| Irritability; Post-Injection 2 |
17.3
4.4%
|
22.3
5.7%
|
| Grade 3 Irritability; Post-Injection 2 |
0.0
0%
|
0.0
0%
|
| Fever; Post-Injection 3 |
20.3
5.2%
|
17.8
4.5%
|
| Grade 3 Fever; Post-Injection 3 |
0.3
0.1%
|
0.3
0.1%
|
| Vomiting; Post-Injection 3 |
7.4
1.9%
|
7.3
1.9%
|
| Grade 3 Vomiting; Post-Injection 3 |
0.3
0.1%
|
0.6
0.2%
|
| Crying abnormal; Post-Injection 3 |
15.1
3.8%
|
14.6
3.7%
|
| Grade 3 Crying abnormal; Post-Injection 3 |
0.0
0%
|
0.0
0%
|
| Drowsiness; Post-Injection 3 |
11.3
2.9%
|
10.7
2.7%
|
| Grade 3 Drowsiness; Post-Injection 3 |
0.0
0%
|
0.0
0%
|
| Appetite lost; Post-Injection 3 |
19.8
5%
|
18.6
4.7%
|
| Grade 3 Appetite lost; Post-Injection 3 |
0.0
0%
|
0.3
0.1%
|
| Irritability; Post-Injection 3 |
14.3
3.6%
|
16.1
4.1%
|
| Grade 3 Irritability; Post-Injection 3 |
0.0
0%
|
0.3
0.1%
|
Adverse Events
| Time Frame | Adverse events (AE) were collected from Day 0 (post-vaccination) of Month 0 up to 6 months post-Injection 3 (up to 573 days). | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | A solicited reaction (SR) was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the eCRF (i.e., solicited) in terms of symptom and/or onset post-vaccination. Safety analysis set. | |||
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group | ||
| Arm/Group Description | Participants received the Stamaril® and the CYD dengue vaccine (Injection 1) at enrolment (M0) at age 12 to 13 months; measles, mumps and rubella vaccine, pneumococcal conjugated vaccine, hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP IPV/Hib) vaccine at M7 (age 19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). | Participants received the Stamaril® vaccine and placebo matched to CYD vaccine (Injection 1) at enrolment (M0) (age 12 to 13 months); measles, mumps, and rubella vaccine, pneumococcal conjugate vaccine and hepatitis A vaccine at M1 (age 13 to 14 months); CYD dengue vaccine (Injection 2) at M6 (age 18 to 19 months); DTaP IPV/Hib vaccine at M7 (age19 to 20 months); and CYD dengue vaccine (Injection 3) at M12 (age 24 to 25 months); and hepatitis A vaccine at M13 (age 25 to 26 months). | ||
All Cause Mortality |
||||
| CYD Dengue Vaccine Group | Placebo Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/394 (0%) | 1/393 (0.3%) | ||
Serious Adverse Events |
||||
| CYD Dengue Vaccine Group | Placebo Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 35/394 (8.9%) | 38/393 (9.7%) | ||
| Blood and lymphatic system disorders | ||||
| Lymphadenitis | 1/394 (0.3%) | 1 | 0/393 (0%) | 0 |
| Lymphadenopathy | 0/394 (0%) | 0 | 1/393 (0.3%) | 1 |
| Gastrointestinal disorders | ||||
| Enteritis | 0/394 (0%) | 0 | 1/393 (0.3%) | 1 |
| Infections and infestations | ||||
| Abscess | 1/394 (0.3%) | 1 | 0/393 (0%) | 0 |
| Acute sinusitis | 2/394 (0.5%) | 2 | 1/393 (0.3%) | 1 |
| Cellulitis | 2/394 (0.5%) | 2 | 1/393 (0.3%) | 1 |
| Cellulitis orbital | 0/394 (0%) | 0 | 1/393 (0.3%) | 1 |
| Dengue fever | 0/394 (0%) | 0 | 1/393 (0.3%) | 1 |
| Diarrhoea infectious | 1/394 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Gastroenteritis | 0/394 (0%) | 0 | 2/393 (0.5%) | 2 |
| Gastroenteritis viral | 1/394 (0.3%) | 1 | 1/393 (0.3%) | 1 |
| Impetigo | 1/394 (0.3%) | 1 | 0/393 (0%) | 0 |
| Meningitis viral | 0/394 (0%) | 0 | 1/393 (0.3%) | 1 |
| Oral herpes | 0/394 (0%) | 0 | 1/393 (0.3%) | 1 |
| Pharyngitis | 0/394 (0%) | 0 | 1/393 (0.3%) | 1 |
| Pneumonia | 12/394 (3%) | 16 | 11/393 (2.8%) | 11 |
| Pneumonia viral | 0/394 (0%) | 0 | 1/393 (0.3%) | 1 |
| Sinusitis | 0/394 (0%) | 0 | 1/393 (0.3%) | 1 |
| Tracheitis | 1/394 (0.3%) | 1 | 0/393 (0%) | 0 |
| Urinary tract infection | 4/394 (1%) | 4 | 3/393 (0.8%) | 3 |
| Viral infection | 0/394 (0%) | 0 | 1/393 (0.3%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Accidental exposure | 1/394 (0.3%) | 1 | 0/393 (0%) | 0 |
| Burns second degree | 1/394 (0.3%) | 1 | 0/393 (0%) | 0 |
| Humerus fracture | 1/394 (0.3%) | 1 | 0/393 (0%) | 0 |
| Thermal burn | 0/394 (0%) | 0 | 1/393 (0.3%) | 1 |
| Tongue injury | 0/394 (0%) | 0 | 1/393 (0.3%) | 1 |
| Traumatic brain injury | 0/394 (0%) | 0 | 1/393 (0.3%) | 1 |
| Metabolism and nutrition disorders | ||||
| Malnutrition | 1/394 (0.3%) | 1 | 0/393 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Acute lymphocytic leukemia | 0/394 (0%) | 0 | 1/393 (0.3%) | 1 |
| Nervous system disorders | ||||
| Convulsion | 0/394 (0%) | 0 | 1/393 (0.3%) | 1 |
| Encephalitis | 0/394 (0%) | 0 | 1/393 (0.3%) | 1 |
| Febrile convulsion | 6/394 (1.5%) | 7 | 4/393 (1%) | 4 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma | 0/394 (0%) | 0 | 1/393 (0.3%) | 1 |
| Asthmatic crisis | 0/394 (0%) | 0 | 1/393 (0.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| CYD Dengue Vaccine Group | Placebo Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 211/394 (53.6%) | 193/393 (49.1%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 61/394 (15.5%) | 73 | 59/393 (15%) | 71 |
| Vomiting; Post-Any injection | 118/386 (30.6%) | 135 | 105/386 (27.2%) | 124 |
| General disorders | ||||
| Injection site Tenderness for Stamaril® vaccine; Post-Any Injection | 98/386 (25.4%) | 98 | 68/386 (17.6%) | 68 |
| Injection site Tenderness for CYD dengue vaccine; Post-Any Injection | 141/386 (36.5%) | 212 | 105/363 (28.9%) | 132 |
| Injection site Tenderness for placebo; Post-Any Injection | 0/394 (0%) | 0 | 76/386 (19.7%) | 76 |
| Injection site Erythema for Stamaril® vaccine; Post-Any Injection | 32/386 (8.3%) | 32 | 38/386 (9.8%) | 38 |
| Injection site Erythema for CYD dengue vaccine; Post-Any Injection | 49/386 (12.7%) | 66 | 32/363 (8.8%) | 44 |
| Injection site Erythema for placebo; Post-Any Injection | 0/394 (0%) | 0 | 42/393 (10.7%) | 42 |
| Injection site Swelling for CYD dengue vaccine; Post-Any Injection | 29/386 (7.5%) | 34 | 22/363 (6.1%) | 27 |
| Fever; Post-Any Injection | 185/385 (48.1%) | 248 | 155/385 (40.3%) | 199 |
| Infections and infestations | ||||
| Gastroenteritis | 44/394 (11.2%) | 46 | 43/393 (10.9%) | 49 |
| Nasopharyngitis | 118/394 (29.9%) | 140 | 120/393 (30.5%) | 140 |
| Pharyngitis | 73/394 (18.5%) | 90 | 52/393 (13.2%) | 65 |
| Metabolism and nutrition disorders | ||||
| Appetite lost; Post-Any injection | 211/394 (53.6%) | 325 | 193/393 (49.1%) | 280 |
| Nervous system disorders | ||||
| Drowsiness; Post-Any Injection | 140/386 (36.3%) | 182 | 131/386 (33.9%) | 183 |
| Psychiatric disorders | ||||
| Crying abnormal; Post-Any injection | 182/394 (46.2%) | 255 | 170/393 (43.3%) | 255 |
| Irritability; Post-Any injection | 179/394 (45.4%) | 265 | 179/393 (45.5%) | 272 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Bronchospasm | 26/394 (6.6%) | 29 | 18/393 (4.6%) | 21 |
| Cough | 24/394 (6.1%) | 27 | 22/393 (5.6%) | 24 |
Limitations/Caveats
None reported
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 subject 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 | Director |
|---|---|
| Organization | Sanofi Pasteur |
| Phone | |
| Contact-US@sanofi.com |
Responsible Party:
Sanofi Pasteur, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT01436396
Other Study ID Numbers:
- CYD29
- U1111-1116-4913
- 2014-001714-26
First Posted:
Sep 19, 2011
Last Update Posted:
Mar 25, 2022
Last Verified:
Mar 1, 2022