Study of a Booster Injection of Pentaxim™ Vaccine Administered With Dengue Vaccine in Healthy Toddlers

• Sponsor: Sanofi Pasteur, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01411241
• Collaborator: (none)
• Enrollment: 720
• Locations: 4
• Arms: 2
• Actual Duration (Months): 32.5
• Patients Per Site: 180
• Patients Per Site Per Month: 5.5

Study Details

Study Description

Brief Summary

The aim of the study was to assess whether the second CYD dengue vaccination could be administered concomitantly with the booster vaccination of a pediatric combination vaccine (Pentaxim™) during the same day visit but in 2 different sites of administration.

Primary Objective:

• To demonstrate the non-inferiority of the antibody response against all antigens (diphtheria, tetanus, pertussis, polio and Haemophilus influenzae type b (Hib)) in participants receiving one booster dose of Pentaxim™ vaccine administered concomitantly with the second dose of CYD dengue vaccine compared to participants receiving one booster dose of Pentaxim™ vaccine administered concomitantly with placebo.

Secondary Objectives:

• To describe the safety of Pentaxim™ vaccine administered concomitantly with the second dose of CYD dengue vaccine, or administered concomitantly with placebo.

• To describe the safety of the CYD dengue vaccine after the second dose of CYD dengue vaccine administered concomitantly with Pentaxim™ vaccine (at Visit 05) or administered alone (at Visit 06).

• To describe the safety of the CYD dengue vaccine in all participants after each dose.

• To describe the antibody response to each dengue virus serotype (post-Dose 2 and post-Dose 3) after the second dose of CYD dengue vaccine administered concomitantly with Pentaxim vaccine (at Visit 05) or administered alone (at Visit 06).

• To describe the antibody response to each dengue virus serotype post-Dose 2 and post-Dose 3.

Condition or Disease	Intervention/Treatment	Phase
Dengue; Dengue Hemorrhagic Fever	Biological: Live, attenuated, recombinant dengue serotype 1, 2, 3, and 4 virus; Biological: DTaP IPV//Hib vaccine; Biological: Placebo; Biological: Measles, mumps, and rubella vaccine; Biological: Pneumococcal vaccine; Biological: Live, attenuated, recombinant dengue serotype 1, 2, 3, and 4 virus; Biological: DTaP IPV//Hib vaccine; Biological: Placebo; Biological: Measles, mumps, and rubella vaccine; Biological: Pneumococcal vaccine	Phase 3

Detailed Description

Participants required 8 or 9 clinic visits and received a total of 7 injections. The dengue post-vaccinal viremia was assessed at Visit 2 from a subset of toddlers. The dengue immunogenicity was assessed 28 days after CYD dengue dose 2 and dose 3 from a subset of toddlers. Participants were followed-up for safety after each vaccine dose and for 6 months after the last dengue vaccination.

Study Design

• Study Type: Interventional
• Actual Enrollment: 720 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: An observer-blind design was chosen since the products were visually different. For the second dose of CYD dengue vaccine, the person who administered the injections knew which product was administered while the subject/parent and Investigator were blinded. The first and third doses of CYD dengue vaccine were administered according to an open-label procedure. A placebo dose was administered at Month 7(Group 1) and concomitantly with Pentaxim vaccine at Month 6 (Group 2) to maintain the blind.
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety of a Booster Injection of DTaP-IPV//Hib (Pentaxim™) Administered Concomitantly With Tetravalent Dengue Vaccine in Healthy Toddlers Aged 15 to 18 Months in Mexico
• Actual Study Start Date: Jul 18, 2011
• Actual Primary Completion Date: Feb 4, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CYD Dengue Vaccine Group 1 Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a measles, mumps, rubella (MMR) vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), a booster dose of Pentaxim vaccine was administered concomitantly with the second injection of CYD dengue vaccine at Month 6 (15 to 18 months of age), placebo at Month 7 (16 to 19 months of age) to maintain the blind, and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).	Biological: Live, attenuated, recombinant dengue serotype 1, 2, 3, and 4 virus; 0.5 mL, subcutaneous at age 9 to 12, 15 to 18 and 21 to 24 months.; Other Names: CYD Dengue Vaccine ; Biological: DTaP IPV//Hib vaccine; 0.5 mL, intramuscular; Other Names: Pentaxim™ ; Biological: Placebo; 0.5 mL, subcutaneous; Other Names: NaCl ; Biological: Measles, mumps, and rubella vaccine; 0.5 mL, subcutaneous; Other Names: Trimovax® ; Biological: Pneumococcal vaccine; 0.5 mL, intramuscular; Other Names: Prevenar®
Experimental: CYD Dengue Vaccine Group 2 Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), the Pentaxim vaccine was administered concomitantly with placebo at Month 6 (15 to 18 months of age) to maintain the blind, a second injection of CYD dengue vaccine at Month 7 (16 to 19 months of age), and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).	Biological: Live, attenuated, recombinant dengue serotype 1, 2, 3, and 4 virus; 0.5 mL, subcutaneous at age 9 to 12, 16 to 19 and 21 to 24 months; Other Names: CYD Dengue Vaccine ; Biological: DTaP IPV//Hib vaccine; 0.5 mL, intramuscular; Other Names: Pentaxim™ ; Biological: Placebo; 0.5 mL, subcutaneously; Other Names: NaCl ; Biological: Measles, mumps, and rubella vaccine; 0.5 mL, subcutaneous; Other Names: Trimovax® ; Biological: Pneumococcal vaccine; 0.5 mL, intramuscular; Other Names: Prevenar®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Seroprotection or Booster Response After a Booster Injection (Inj.) of Diphtheria, Tetanus, Acellular Pertussis(DTaP)-Inactivated Polio Virus (IPV)//Hib (Pentaxim™) Administered Concomitantly With CYD Dengue Vaccine [28 days post-injection]

   Antibodies (Ab) against diphtheria, tetanus toxoid, pertussis toxoid (PT), and filamentous hemaglutinin (FHA) was measured by enzyme-linked immunosorbent assay (ELISA), polyribosylribitol phosphate (PRP) by Farr-type radioimmunoassay, and poliovirus types 1, 2, and 3 by seroneutralization assay. Seroprotection was defined as >=0.1 International Unit (IU)/mL for diphtheria toxoid and tetanus toxoid, >=8 1/dil for poliovirus types 1, 2, and 3, and >=1.0 μg/mL for PRP. Booster response to PT and FHA: participants whose pre-vaccination Ab titers were < lower limit of quantitation (LLOQ), a booster response occurred if they had post-vaccination levels >=4* LLOQ; participants whose pre-vaccination Ab concentrations were >=LLOQ but <4* LLOQ, a booster response occurred if they had a 4-fold increase (post/pre-vaccination levels >=4); for participants whose pre-vaccination Ab concentrations were >=4* LLOQ, a booster response occurred if they had a 2-fold increase (post/pre-vaccination >=2).

Secondary Outcome Measures

1. Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains Before and After a Booster Injection of DTaP-IPV//Hib (Pentaxim™) Administered Concomitantly With CYD Dengue Vaccine [Pre-injection 1 and 28 days post-injection 2 and 3]

   Geometric mean titers of antibodies against the dengue virus serotypes were measured by dengue plaque reduction neutralization test (PRNT).

2. Geometric Mean Titer Ratios Against Each Serotype With the Parental of Dengue Virus Strains Before and After a Booster Injection of DTaP-IPV//Hib (Pentaxim™) Administered Concomitantly With CYD Dengue Vaccine [Pre-injection 1 and 28 days post-injection 2 and 3]

   Geometric mean titers of antibodies against the dengue virus serotypes were measured by dengue PRNT.

3. Percentage of Participants With a Seropositivity Against Each Serotype With the Parental Dengue Virus Strains Before and After a Booster Injection of DTaP-IPV//Hib (Pentaxim™) Administered Concomitantly With CYD Dengue Vaccine [Pre-injection 1 and 28 days post-injection 2 and 3]

   Seropositivity against each dengue virus serotype (parental strains) were measured by dengue PRNT. Seropositivity was defined as antibody titers >=10 (1/dilution).

4. Percentage of Participants With Seropositivity Against at Least One, Two, Three, or Four Serotypes With the Parental Dengue Virus Strains Before and After a Booster Injection of DTaP-IPV// Hib (Pentaxim™) Administered With CYD Dengue Vaccine [Pre-injection 1 and 28 days post-injection 2 and 3]

   Seropositivity against each dengue virus serotype (parental strains) were measured by dengue PRNT. Seropositivity was defined as antibody titers >=10 (1/dilution).

5. Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following the First Injection With CYD Dengue Vaccine [Day 0 up to Day 14 post-first injection]

   Solicited injection site reactions: Tenderness, Erythema, and Swelling. Solicited systemic reactions: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, and Irritability. Grade (Grd) 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 mm. Grade 3 Solicited systemic reactions: Fever: >39.5 degree Celsius (°C); Vomiting: >=6 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.

6. Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Booster Injection of DTaP-IPV// Hib (Pentaxim™) Administered Concomitantly With Either CYD Dengue Vaccine or a Placebo Vaccine [Day 0 up to Day 14 post-booster injection]

   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 mm. Grade 3 Solicited systemic reactions: Fever: >39.5°C; Vomiting: >=6 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; and Extensive swelling, severe.

7. Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Second Injection of CYD Dengue Vaccine or a Placebo Vaccine [Day 0 up to Day 14 post-second injection]

   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 mm. Grade 3 Solicited systemic reactions: Fever: >39.5°C; Vomiting: >=6 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.

8. Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Third Injection of CYD Dengue Vaccine [Day 0 up to Day 14 post-third injection]

   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 mm. Grade 3 Solicited systemic reactions: Fever: >39.5°C; Vomiting: >=6 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 9 Months to 12 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Aged 9 to 12 months on the day of inclusion.

• Born at full term of pregnancy (>= 37 weeks) and with a birth weight >= 2.5 kg.

• Participant in good health, based on medical history and physical examination.

• Documentation of completion of the primary vaccination series with Pentaxim vaccine with the 3 doses received between 2 and 8 months of age.

• Informed consent form had been signed and dated by both parents or other legally acceptable representative (and by 2 mandatory witnesses as required by local regulations).

• Participant and parent/guardian attended all scheduled visits and 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 any trial vaccination.

• Previous vaccination against flavivirus diseases, measles, mumps, rubella, previous booster vaccination against pneumococcal diseases, diphtheria, tetanus, pertussis, Hib and/or polio.

• 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 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).

• Personal seropositivity for human immunodeficiency virus (HIV) or hepatitis C as reported by the parent(s)/legally acceptable representative.

• History of pertussis and/or Hib infection as reported by the parent(s)/legally acceptable representative.

• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances.

• History of contraindication to the receipt of vaccines containing components of Pentaxim vaccine (diphtheria toxoid, tetanus toxoid, pertussis toxoid, filamentous hemagglutinin, polyribosylribitol phosphate [PRP] and polio) or of measles, mumps and rubella vaccine and of pneumococcal vaccine.

• Thrombocytopenia, as reported by the parent(s)/legally acceptable representative.

• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination.

• History of central nervous system disorder or disease, including seizures.

• 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 site 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		Acapulco	Guerrero	Mexico	CP 39670
2		Guadalajara	Jalisco	Mexico	CP 44280
3		Monterrey	Nuevo Leon	Mexico	CP 64460
4		Merida	Yucatan	Mexico	CP 97000

Sponsors and Collaborators

• Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director, Sanofi Pasteur SA

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01411241
• Other Study ID Numbers: CYD33; U1111-1115-6290
• First Posted: Aug 8, 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: Dengue; Dengue Hemorrhagic Fever; CYD Dengue Vaccines; Pentaxim™
• Additional relevant MeSH terms: Dengue; Hemorrhagic Fevers, Viral; Severe Dengue; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine

Study Results

Participant Flow

Recruitment Details	Study participants were enrolled from 18 July 2011 to 31 July 2012 at 3 clinical sites in Mexico. The study planned for 732 participants; however, recruitment was stopped when 720 participants were enrolled due to the difficulty in enrolling participants.
Pre-assignment Detail	A total of 720 participants who met all of the inclusion criteria and none of the exclusion criteria were enrolled, out of which 309 participants were randomized to Group 1 and 315 in Group 2, and 96 participants were not randomized to Group 1 or 2.

Arm/Group Title	CYD Dengue Vaccine Group 1	CYD Dengue Vaccine Group 2
Arm/Group Description	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a measles, mumps, rubella (MMR) vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), a booster dose of Pentaxim vaccine was administered concomitantly with the second injection of CYD dengue vaccine at Month 6 (15 to 18 months of age), placebo at Month 7 (16 to 19 months of age) to maintain the blind, and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), the Pentaxim vaccine was administered concomitantly with placebo at Month 6 (15 to 18 months of age) to maintain the blind, a second injection of CYD dengue vaccine at Month 7 (16 to 19 months of age), and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).
Period Title: Overall Study
STARTED	309	315
COMPLETED	298	293
NOT COMPLETED	11	22

Baseline Characteristics

Arm/Group Title	CYD Dengue Vaccine Group 1	CYD Dengue Vaccine Group 2	Total
Arm/Group Description	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), a booster dose of Pentaxim vaccine was administered concomitantly with the second injection of CYD dengue vaccine at Month 6 (15 to 18 months of age), placebo at Month 7 (16 to 19 months of age) to maintain the blind, and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), the Pentaxim vaccine was administered concomitantly with placebo at Month 6 (15 to 18 months of age) to maintain the blind, a second injection of CYD dengue vaccine at Month 7 (16 to 19 months of age), and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).	Total of all reporting groups
Overall Participants	309	315	624
Age, Customized (Count of Participants)
1 month to 23 months	309 100%	315 100%	624 100%
Sex: Female, Male (Count of Participants)
Female	146 47.2%	139 44.1%	285 45.7%
Male	163 52.8%	176 55.9%	339 54.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Seroprotection or Booster Response After a Booster Injection (Inj.) of Diphtheria, Tetanus, Acellular Pertussis(DTaP)-Inactivated Polio Virus (IPV)//Hib (Pentaxim™) Administered Concomitantly With CYD Dengue Vaccine
Description	Antibodies (Ab) against diphtheria, tetanus toxoid, pertussis toxoid (PT), and filamentous hemaglutinin (FHA) was measured by enzyme-linked immunosorbent assay (ELISA), polyribosylribitol phosphate (PRP) by Farr-type radioimmunoassay, and poliovirus types 1, 2, and 3 by seroneutralization assay. Seroprotection was defined as >=0.1 International Unit (IU)/mL for diphtheria toxoid and tetanus toxoid, >=8 1/dil for poliovirus types 1, 2, and 3, and >=1.0 μg/mL for PRP. Booster response to PT and FHA: participants whose pre-vaccination Ab titers were < lower limit of quantitation (LLOQ), a booster response occurred if they had post-vaccination levels >=4* LLOQ; participants whose pre-vaccination Ab concentrations were >=LLOQ but <4* LLOQ, a booster response occurred if they had a 4-fold increase (post/pre-vaccination levels >=4); for participants whose pre-vaccination Ab concentrations were >=4* LLOQ, a booster response occurred if they had a 2-fold increase (post/pre-vaccination >=2).
Time Frame	28 days post-injection

Outcome Measure Data

Analysis Population Description

Per-protocol analysis set:all participants who had no protocol deviations (not meet inclusion/exclusion criteria,not received vaccine in time window, administration not done per protocol) and could impact Pentaxim vaccine immunogenicity up to Visit 06 (Month 07). Here, 'number analyzed'=participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine Group 1	CYD Dengue Vaccine Group 2
Arm/Group Description	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), a booster dose of Pentaxim vaccine was administered concomitantly with the second injection of CYD dengue vaccine at Month 6 (15 to 18 months of age), placebo at Month 7 (16 to 19 months of age) to maintain the blind, and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), the Pentaxim vaccine was administered concomitantly with placebo at Month 6 (15 to 18 months of age) to maintain the blind, a second injection of CYD dengue vaccine at Month 7 (16 to 19 months of age), and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).
Measure Participants	256	270
Anti-diphtheria	100.0 32.4%	100.0 31.7%
Anti-tetanus	100.0 32.4%	99.6 31.6%
Anti-polio 1	100.0 32.4%	99.6 31.6%
Anti-polio 2	100.0 32.4%	100.0 31.7%
Anti-polio 3	100 32.4%	99.6 31.6%
Anti-PRP	100.0 32.4%	100.0 31.7%
Anti-PT	96.5 31.2%	97.0 30.8%
Anti-FHA	93.0 30.1%	93.3 29.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group 1, CYD Dengue Vaccine Group 2
	Comments	Non-inferiority (Group 1 - Group 2); Anti-diphtheria. Non-inferiority of Pentaxim booster dose based on seroprotection/booster response was assessed 28 days after injection.
	Type of Statistical Test	Non-Inferiority
	Comments	The non-inferiority was demonstrated if the lower limit of all the 95% Confidence Interval (CI) of the difference is greater than -10% for all antigens. Wilson score (without continuity adjustment) 95% two-sided CI was used for the difference of seroprotection/booster rates.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -1.48 to 1.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group 1, CYD Dengue Vaccine Group 2
	Comments	Non-inferiority (Group 1 - Group 2); Anti-tetanus. Non-inferiority of Pentaxim booster dose based on seroprotection/booster response was assessed 28 days after injection.
	Type of Statistical Test	Non-Inferiority
	Comments	The non-inferiority was demonstrated if the lower limit of all the 95% CI of the difference is greater than -10% for all antigens. Wilson score (without continuity adjustment) 95% two-sided CI was used for the difference of seroprotection/booster rates.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 95%; -1.14 to 2.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group 1, CYD Dengue Vaccine Group 2
	Comments	Non-inferiority (Group 1 - Group 2); Anti-polio 1. Non-inferiority of Pentaxim booster dose based on seroprotection/booster response was assessed 28 days after injection.
	Type of Statistical Test	Non-Inferiority
	Comments	The non-inferiority was demonstrated if the lower limit of all the 95% CI of the difference is greater than -10% for all antigens. Wilson score (without continuity adjustment) 95% two-sided CI was used for the difference of seroprotection/booster rates.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 95%; -1.14 to 2.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group 1, CYD Dengue Vaccine Group 2
	Comments	Non-inferiority (Group 1 - Group 2); Anti-polio 2. Non-inferiority of Pentaxim booster dose based on seroprotection/booster response was assessed 28 days after injection.
	Type of Statistical Test	Non-Inferiority
	Comments	The non-inferiority was demonstrated if the lower limit of all the 95% CI of the difference is greater than -10% for all antigens. Wilson score (without continuity adjustment) 95% two-sided CI was used for the difference of seroprotection/booster rates.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -1.48 to 1.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group 1, CYD Dengue Vaccine Group 2
	Comments	Non-inferiority (Group 1 - Group 2); Anti-polio 3. Non-inferiority of Pentaxim booster dose based on seroprotection/booster response was assessed 28 days after injection.
	Type of Statistical Test	Non-Inferiority
	Comments	The non-inferiority was demonstrated if the lower limit of all the 95% CI of the difference is greater than -10% for all antigens. Wilson score (without continuity adjustment) 95% two-sided CI was used for the difference of seroprotection/booster rates.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 95%; -1.15 to 2.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group 1, CYD Dengue Vaccine Group 2
	Comments	Non-inferiority (Group 1 - Group 2); Anti-PRP. Non-inferiority of Pentaxim booster dose based on seroprotection/booster response was assessed 28 days after injection.
	Type of Statistical Test	Non-Inferiority
	Comments	The non-inferiority was demonstrated if the lower limit of all the 95% CI of the difference is greater than -10% for all antigens. Wilson score (without continuity adjustment) 95% two-sided CI was used for the difference of seroprotection/booster rates.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -1.48 to 1.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group 1, CYD Dengue Vaccine Group 2
	Comments	Non-inferiority (Group 1 - Group 2); Anti-PT. Non-inferiority of Pentaxim booster dose based on seroprotection/booster response was assessed 28 days after injection.
	Type of Statistical Test	Non-Inferiority
	Comments	The non-inferiority was demonstrated if the lower limit of all the 95% CI of the difference is greater than -10% for all antigens. Wilson score (without continuity adjustment) 95% two-sided CI was used for the difference of seroprotection/booster rates.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	-0.56
	Confidence Interval	(2-Sided) 95%; -3.93 to 2.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group 1, CYD Dengue Vaccine Group 2
	Comments	Non-inferiority (Group 1 - Group 2); Anti-FHA. Non-inferiority of Pentaxim booster dose based on seroprotection/booster response was assessed 28 days after injection.
	Type of Statistical Test	Non-Inferiority
	Comments	The non-inferiority was demonstrated if the lower limit of all the 95% CI of the difference is greater than -10% for all antigens. Wilson score (without continuity adjustment) 95% two-sided CI was used for the difference of seroprotection/booster rates.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -4.87 to 4.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains Before and After a Booster Injection of DTaP-IPV//Hib (Pentaxim™) Administered Concomitantly With CYD Dengue Vaccine
Description	Geometric mean titers of antibodies against the dengue virus serotypes were measured by dengue plaque reduction neutralization test (PRNT).
Time Frame	Pre-injection 1 and 28 days post-injection 2 and 3

Outcome Measure Data

Analysis Population Description

Analysis was performed on Full analysis set for dengue immunogenicity which included participants randomized into the dengue immunogenicity subset who received at least one dose of CYD dengue vaccine. Here, 'number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine Group 1	CYD Dengue Vaccine Group 2
Arm/Group Description	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), a booster dose of Pentaxim vaccine was administered concomitantly with the second injection of CYD dengue vaccine at Month 6 (15 to 18 months of age), placebo at Month 7 (16 to 19 months of age) to maintain the blind, and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), the Pentaxim vaccine was administered concomitantly with placebo at Month 6 (15 to 18 months of age) to maintain the blind, a second injection of CYD dengue vaccine at Month 7 (16 to 19 months of age), and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).
Measure Participants	109	107
Serotype 1; Pre-injection 1	5.28	5.35
Serotype 1; Post-injection 2	39.8	62.8
Serotype 1; Post-injection 3	93.1	97.0
Serotype 2; Pre-injection 1	5.22	5.53
Serotype 2; Post-injection 2	109	121
Serotype 2; Post-injection 3	189	208
Serotype 3; Pre-injection 1	5.26	5.38
Serotype 3; Post-injection 2	92.8	116
Serotype 3; Post-injection 3	196	217
Serotype 4; Pre-injection 1	5.11	5.00
Serotype 4; Post-injection 2	57.8	104
Serotype 4; Post-injection 3	121	127

3. Secondary Outcome

Title	Geometric Mean Titer Ratios Against Each Serotype With the Parental of Dengue Virus Strains Before and After a Booster Injection of DTaP-IPV//Hib (Pentaxim™) Administered Concomitantly With CYD Dengue Vaccine
Description	Geometric mean titers of antibodies against the dengue virus serotypes were measured by dengue PRNT.
Time Frame	Pre-injection 1 and 28 days post-injection 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 1	CYD Dengue Vaccine Group 2
Arm/Group Description	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), a booster dose of Pentaxim vaccine was administered concomitantly with the second injection of CYD dengue vaccine at Month 6 (15 to 18 months of age), placebo at Month 7 (16 to 19 months of age) to maintain the blind, and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), the Pentaxim vaccine was administered concomitantly with placebo at Month 6 (15 to 18 months of age) to maintain the blind, a second injection of CYD dengue vaccine at Month 7 (16 to 19 months of age), and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).
Measure Participants	109	107
Serotype 1: Post-inj 2 value/pre-inj 1 value	3.81	5.97
Serotype 1: Post-inj 3 value/pre-inj 1 value	8.91	9.20
Serotype 2: Post-inj 2 value/pre-inj 1 value	10.6	11.5
Serotype 2: Post-inj 3 value/pre-inj 1 value	18.3	19.6
Serotype 3: Post-inj 2 value/pre-inj 1 value	8.97	11.1
Serotype 3: Post-inj 3 value/pre-inj 1 value	19.1	20.6
Serotype 4: Post-inj 2 value/pre-inj 1 value	5.73	10.0
Serotype 4: Post-inj 3 value/pre-inj 1 value	12.0	12.6

4. Secondary Outcome

Title	Percentage of Participants With a Seropositivity Against Each Serotype With the Parental Dengue Virus Strains Before and After a Booster Injection of DTaP-IPV//Hib (Pentaxim™) Administered Concomitantly With CYD Dengue Vaccine
Description	Seropositivity against each dengue virus serotype (parental strains) were measured by dengue PRNT. Seropositivity was defined as antibody titers >=10 (1/dilution).
Time Frame	Pre-injection 1 and 28 days post-injection 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 1	CYD Dengue Vaccine Group 2
Arm/Group Description	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), a booster dose of Pentaxim vaccine was administered concomitantly with the second injection of CYD dengue vaccine at Month 6 (15 to 18 months of age), placebo at Month 7 (16 to 19 months of age) to maintain the blind, and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), the Pentaxim vaccine was administered concomitantly with placebo at Month 6 (15 to 18 months of age) to maintain the blind, a second injection of CYD dengue vaccine at Month 7 (16 to 19 months of age), and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).
Measure Participants	109	107
Serotype 1; Pre-injection 1	1.8 0.6%	2.8 0.9%
Serotype 1; Post-injection 2	84.8 27.4%	92.2 29.3%
Serotype 1; Post-injection 3	100.0 32.4%	100.0 31.7%
Serotype 2; Pre-injection 1	1.8 0.6%	4.7 1.5%
Serotype 2; Post-injection 2	98.1 31.7%	96.1 30.5%
Serotype 2; Post-injection 3	100.0 32.4%	100.0 31.7%
Serotype 3; Pre-injection 1	2.8 0.9%	3.7 1.2%
Serotype 3; Post-injection 2	100.0 32.4%	98.1 31.1%
Serotype 3; Post-injection 3	100.0 32.4%	100.0 31.7%
Serotype 4; Pre-injection 1	1.8 0.6%	0.0 0%
Serotype 4; Post-injection 2	90.5 29.3%	96.1 30.5%
Serotype 4; Post-injection 3	100.0 32.4%	100.0 31.7%

5. Secondary Outcome

Title	Percentage of Participants With Seropositivity Against at Least One, Two, Three, or Four Serotypes With the Parental Dengue Virus Strains Before and After a Booster Injection of DTaP-IPV// Hib (Pentaxim™) Administered With CYD Dengue Vaccine
Description	Seropositivity against each dengue virus serotype (parental strains) were measured by dengue PRNT. Seropositivity was defined as antibody titers >=10 (1/dilution).
Time Frame	Pre-injection 1 and 28 days post-injection 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 1	CYD Dengue Vaccine Group 2
Arm/Group Description	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), a booster dose of Pentaxim vaccine was administered concomitantly with the second injection of CYD dengue vaccine at Month 6 (15 to 18 months of age), placebo at Month 7 (16 to 19 months of age) to maintain the blind, and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), the Pentaxim vaccine was administered concomitantly with placebo at Month 6 (15 to 18 months of age) to maintain the blind, a second injection of CYD dengue vaccine at Month 7 (16 to 19 months of age), and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).
Measure Participants	109	107
At least 1 serotype; Pre-injection 1	4.6 1.5%	8.4 2.7%
At least 1 serotype; Post-injection 2	100.0 32.4%	100.0 31.7%
At least 1 serotype; Post-injection 3	100.0 32.4%	100.0 31.7%
At least 2 serotypes; Pre-injection 1	1.8 0.6%	1.9 0.6%
At least 2 serotypes; Post-injection 2	100.0 32.4%	98.1 31.1%
At least 2 serotypes; Post-injection 3	100.0 32.4%	100.0 31.7%
At least 3 serotypes; Pre-injection 1	0.9 0.3%	0.9 0.3%
At least 3 serotypes; Post-injection 2	94.3 30.5%	95.1 30.2%
At least 3 serotypes; Post-injection 3	100.0 32.4%	100.0 31.7%
All 4 serotypes; Pre-injection 1	0.9 0.3%	0.0 0%
All 4 serotypes; Post-injection 2	79.0 25.6%	89.3 28.3%
All 4 serotypes; Post-injection 3	100.0 32.4%	100.0 31.7%

6. Secondary Outcome

Title	Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following the First Injection With CYD Dengue Vaccine
Description	Solicited injection site reactions: Tenderness, Erythema, and Swelling. Solicited systemic reactions: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, and Irritability. Grade (Grd) 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 mm. Grade 3 Solicited systemic reactions: Fever: >39.5 degree Celsius (°C); Vomiting: >=6 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.
Time Frame	Day 0 up to Day 14 post-first injection

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety analysis set which included participants who received at least one dose of CYD dengue vaccine, Pentaxim vaccine or placebo. Here, 'number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine Group 1	CYD Dengue Vaccine Group 2
Arm/Group Description	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), a booster dose of Pentaxim vaccine was administered concomitantly with the second injection of CYD dengue vaccine at Month 6 (15 to 18 months of age), placebo at Month 7 (16 to 19 months of age) to maintain the blind, and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), the Pentaxim vaccine was administered concomitantly with placebo at Month 6 (15 to 18 months of age) to maintain the blind, a second injection of CYD dengue vaccine at Month 7 (16 to 19 months of age), and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).
Measure Participants	309	315
Injection site Tenderness	29.9 9.7%	33.3 10.6%
Grade 3 Injection site Tenderness	0.3 0.1%	0.0 0%
Injection site Erythema	14.0 4.5%	15.7 5%
Grade 3 Injection site Erythema	0.0 0%	0.0 0%
Injection site Swelling	4.9 1.6%	10.9 3.5%
Grade 3 Injection site Swelling	0.0 0%	0.3 0.1%
Fever	25.1 8.1%	28.1 8.9%
Grade 3 Fever	1.6 0.5%	0.0 0%
Vomiting	18.8 6.1%	17.6 5.6%
Grade 3 Vomiting	1.3 0.4%	0.6 0.2%
Crying abnormal	36.4 11.8%	38.5 12.2%
Grade 3 Crying abnormal	2.3 0.7%	2.2 0.7%
Drowsiness	24.0 7.8%	23.4 7.4%
Grade 3 Drowsiness	1.9 0.6%	1.6 0.5%
Appetite lost	32.5 10.5%	34.7 11%
Grade 3 Appetite lost	4.5 1.5%	4.5 1.4%
Injection site Irritability	47.1 15.2%	45.5 14.4%
Grade 3 Injection site Irritability	3.2 1%	4.2 1.3%

7. Secondary Outcome

Title	Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Booster Injection of DTaP-IPV// Hib (Pentaxim™) Administered Concomitantly With Either CYD Dengue Vaccine or a Placebo Vaccine
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 mm. Grade 3 Solicited systemic reactions: Fever: >39.5°C; Vomiting: >=6 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; and Extensive swelling, severe.
Time Frame	Day 0 up to Day 14 post-booster injection

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety analysis set. 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 1	CYD Dengue Vaccine Group 2
Arm/Group Description	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), a booster dose of Pentaxim vaccine was administered concomitantly with the second injection of CYD dengue vaccine at Month 6 (15 to 18 months of age), placebo at Month 7 (16 to 19 months of age) to maintain the blind, and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), the Pentaxim vaccine was administered concomitantly with placebo at Month 6 (15 to 18 months of age) to maintain the blind, a second injection of CYD dengue vaccine at Month 7 (16 to 19 months of age), and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).
Measure Participants	309	314
Injection site Tenderness	43.2 14%	42.3 13.4%
Grade 3 Injection site Tenderness	1.0 0.3%	0.7 0.2%
Injection site Tenderness; Post- Pentaxim	37.5 12.1%	37.7 12%
Grade 3 Injection site Tenderness; Post- Pentaxim	1.0 0.3%	0.7 0.2%
Injection site Tenderness; Post-CYD dengue/placebo	33.2 10.7%	30.5 9.7%
Grd 3 Inj. site Tenderness;Post-CYD dengue/placebo	0.0 0%	0.3 0.1%
Injection site Erythema	15.0 4.9%	20.3 6.4%
Grade 3 Injection site Erythema	0.3 0.1%	0.0 0%
Injection site Erythema; Post-Pentaxim	13.0 4.2%	17.8 5.7%
Grade 3 Injection site Erythema; Post- Pentaxim	0.3 0.1%	0.0 0%
Injection site Erythema; Post-CYD dengue/placebo	8.3 2.7%	13.1 4.2%
Grd 3 Inj. site Erythema; Post-CYD dengue/placebo	0.0 0%	0.0 0%
Injection site Swelling	11.6 3.8%	17.0 5.4%
Grade 3 Injection site Swelling	0.3 0.1%	0.0 0%
Injection site Swelling; Post-Pentaxim	9.4 3%	16.1 5.1%
Grade 3 Injection site Swelling; Post- Pentaxim	0.3 0.1%	0.0 0%
Injection site Swelling; Post-CYD dengue/placebo	5.0 1.6%	7.2 2.3%
Grd 3 Inj. site Swelling; Post-CYD dengue/placebo	0.0 0%	0.0 0%
Injection site extensive swelling; Post- Pentaxim	0.0 0%	0.0 0%
Grd 3 Inj. site extensive swelling; Post- Pentaxim	0.0 0%	0.0 0%
Fever	29.1 9.4%	24.3 7.7%
Grade 3 Fever	1.0 0.3%	0.0 0%
Vomiting	11.7 3.8%	11.8 3.7%
Grade 3 Vomiting	1.0 0.3%	0.0 0%
Crying abnormal	33.7 10.9%	30.8 9.8%
Grade 3 Crying abnormal	0.7 0.2%	1.6 0.5%
Drowsiness	19.7 6.4%	17.0 5.4%
Grade 3 Drowsiness	1.0 0.3%	0.7 0.2%
Appetite lost	23.3 7.5%	23.0 7.3%
Grade 3 Appetite lost	3.7 1.2%	3.0 1%
Irritability	37.7 12.2%	39.7 12.6%
Grade 3 Irritability	1.0 0.3%	0.7 0.2%

8. Secondary Outcome

Title	Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Second Injection of CYD Dengue Vaccine or a Placebo Vaccine
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 mm. Grade 3 Solicited systemic reactions: Fever: >39.5°C; Vomiting: >=6 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.
Time Frame	Day 0 up to Day 14 post-second injection

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety analysis set. 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 1	CYD Dengue Vaccine Group 2
Arm/Group Description	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), a booster dose of Pentaxim vaccine was administered concomitantly with the second injection of CYD dengue vaccine at Month 6 (15 to 18 months of age), placebo at Month 7 (16 to 19 months of age) to maintain the blind, and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), the Pentaxim vaccine was administered concomitantly with placebo at Month 6 (15 to 18 months of age) to maintain the blind, a second injection of CYD dengue vaccine at Month 7 (16 to 19 months of age), and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).
Measure Participants	301	302
Injection site Tenderness	24.5 7.9%	25.7 8.2%
Grade 3 Injection site Tenderness	0.0 0%	0.0 0%
Injection site Erythema	8.2 2.7%	10.1 3.2%
Grade 3 Injection site Erythema	0.0 0%	0.0 0%
Injection site Swelling	4.4 1.4%	5.1 1.6%
Grade 3 Injection site Swelling	0.0 0%	0.3 0.1%
Fever	16.7 5.4%	18.1 5.7%
Grade 3 Fever	0.0 0%	0.7 0.2%
Vomiting	6.8 2.2%	8.8 2.8%
Grade 3 Vomiting	0.3 0.1%	0.0 0%
Crying abnormal	21.2 6.9%	24.3 7.7%
Grade 3 Crying abnormal	0.0 0%	0.3 0.1%
Drowsiness	11.9 3.9%	14.9 4.7%
Grade 3 Drowsiness	0.0 0%	0.0 0%
Appetite lost	17.7 5.7%	20.9 6.6%
Grade 3 Appetite lost	1.7 0.6%	1.7 0.5%
Irritability	23.9 7.7%	25.3 8%
Grade 3 Irritability	0.3 0.1%	1.0 0.3%

9. Secondary Outcome

Title	Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Third Injection of CYD Dengue Vaccine
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 mm. Grade 3 Solicited systemic reactions: Fever: >39.5°C; Vomiting: >=6 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.
Time Frame	Day 0 up to Day 14 post-third injection

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety analysis set. 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 1	CYD Dengue Vaccine Group 2
Arm/Group Description	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), a booster dose of Pentaxim vaccine was administered concomitantly with the second injection of CYD dengue vaccine at Month 6 (15 to 18 months of age), placebo at Month 7 (16 to 19 months of age) to maintain the blind, and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), the Pentaxim vaccine was administered concomitantly with placebo at Month 6 (15 to 18 months of age) to maintain the blind, a second injection of CYD dengue vaccine at Month 7 (16 to 19 months of age), and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).
Measure Participants	298	297
Injection site Tenderness	19.8 6.4%	25.4 8.1%
Grade 3 Injection site Tenderness	0.0 0%	0.0 0%
Injection site Erythema	6.7 2.2%	5.8 1.8%
Grade 3 Injection site Erythema	0.0 0%	0.0 0%
Injection site Swelling	2.0 0.6%	2.7 0.9%
Grade 3 Injection site Swelling	0.0 0%	0.0 0%
Fever	16.0 5.2%	15.2 4.8%
Grade 3 Fever	1.0 0.3%	0.0 0%
Vomiting	4.4 1.4%	7.2 2.3%
Grade 3 Vomiting	0.7 0.2%	1.0 0.3%
Crying abnormal	21.5 7%	18.9 6%
Grade 3 Crying abnormal	0.7 0.2%	0.3 0.1%
Drowsiness	10.4 3.4%	10.0 3.2%
Grade 3 Drowsiness	0.7 0.2%	0.7 0.2%
Appetite lost	18.8 6.1%	18.6 5.9%
Grade 3 Appetite lost	1.3 0.4%	2.4 0.8%
Irritability	23.8 7.7%	20.6 6.5%
Grade 3 Irritability	1.0 0.3%	0.0 0%

Adverse Events

Time Frame	Adverse event data were collected from Day 0 (post-vaccination) up to 6 months post-third CYD injection (up to 18 months).
Adverse Event Reporting Description	Analysis was performed on Safety analysis set.
Arm/Group Title	CYD Dengue Vaccine Group 1		CYD Dengue Vaccine Group 2
Arm/Group Description	Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), a booster dose of Pentaxim vaccine was administered concomitantly with the second injection of CYD dengue vaccine at Month 6 (15 to 18 months of age), placebo at Month 7 (16 to 19 months of age) to maintain the blind, and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).		Participants received the first injection of CYD dengue vaccine at Month 0 (9 to 12 months of age), a MMR vaccine and pneumococcal conjugate vaccine at Month 1 (10 to 13 months of age), the Pentaxim vaccine was administered concomitantly with placebo at Month 6 (15 to 18 months of age) to maintain the blind, a second injection of CYD dengue vaccine at Month 7 (16 to 19 months of age), and the third injection of CYD dengue vaccine at Month 12 (21 to 24 months).
All Cause Mortality
	CYD Dengue Vaccine Group 1		CYD Dengue Vaccine Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/309 (0%)		1/315 (0.3%)
Serious Adverse Events
	CYD Dengue Vaccine Group 1		CYD Dengue Vaccine Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/309 (5.5%)		21/315 (6.7%)
Blood and lymphatic system disorders
Thrombocytopenic purpura	0/309 (0%)	0	1/315 (0.3%)	1
Congenital, familial and genetic disorders
Phimosis	1/309 (0.3%)	1	0/315 (0%)	0
Gastrointestinal disorders
Diarrhoea	1/309 (0.3%)	1	1/315 (0.3%)	1
Infections and infestations
Amoebic dysentery	1/309 (0.3%)	1	0/315 (0%)	0
Ascariasis	1/309 (0.3%)	1	0/315 (0%)	0
Bronchopneumonia	0/309 (0%)	0	2/315 (0.6%)	3
Cellulitis	1/309 (0.3%)	1	0/315 (0%)	0
Dengue fever	1/309 (0.3%)	1	0/315 (0%)	0
Gastroenteritis	1/309 (0.3%)	1	0/315 (0%)	0
Gastroenteritis bacterial	1/309 (0.3%)	1	0/315 (0%)	0
Gastroenteritis viral	1/309 (0.3%)	1	0/315 (0%)	0
Pneumonia	0/309 (0%)	0	1/315 (0.3%)	1
Injury, poisoning and procedural complications
Accidental exposure	0/309 (0%)	0	1/315 (0.3%)	1
Burns second degree	0/309 (0%)	0	1/315 (0.3%)	1
Head injury	1/309 (0.3%)	1	0/315 (0%)	0
Road traffic accident	0/309 (0%)	0	1/315 (0.3%)	1
Thermal burn	0/309 (0%)	0	1/315 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myelomonocytic leukaemia	0/309 (0%)	0	1/315 (0.3%)	1
Nervous system disorders
Encephalitis	0/309 (0%)	0	1/315 (0.3%)	1
Febrile convulsion	5/309 (1.6%)	6	7/315 (2.2%)	10
Respiratory, thoracic and mediastinal disorders
Asthma	0/309 (0%)	0	1/315 (0.3%)	1
Asthmatic crisis	2/309 (0.6%)	2	1/315 (0.3%)	1
Bronchial hyperreactivity	0/309 (0%)	0	1/315 (0.3%)	1
Respiratory distress	0/309 (0%)	0	1/315 (0.3%)	1
Other (Not Including Serious) Adverse Events
	CYD Dengue Vaccine Group 1		CYD Dengue Vaccine Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	145/309 (46.9%)		142/315 (45.1%)
Gastrointestinal disorders
Diarrhoea	34/309 (11%)	41	34/315 (10.8%)	37
Vomiting; Post-injection 1	58/308 (18.8%)	58	55/312 (17.6%)	55
General disorders
Injection site Tenderness; Post-injection 1	92/309 (29.8%)	92	104/312 (33.3%)	104
Injection site Erythema; Post-injection 1	43/308 (14%)	43	49/312 (15.7%)	49
Injection site Swelling; Post-injection 1	15/308 (4.9%)	15	34/312 (10.9%)	34
Fever; Post-injection 1	77/307 (25.1%)	77	88/313 (28.1%)	88
Infections and infestations
Gastroenteritis	55/309 (17.8%)	61	47/315 (14.9%)	51
Nasopharyngitis	109/309 (35.3%)	147	104/315 (33%)	132
Pharyngitis	50/309 (16.2%)	60	57/315 (18.1%)	69
Pharyngotonsillitis	24/309 (7.8%)	28	33/315 (10.5%)	33
Rhinitis	25/309 (8.1%)	26	22/315 (7%)	26
Metabolism and nutrition disorders
Appetite lost; Post-injection 1	100/308 (32.5%)	100	108/311 (34.7%)	108
Nervous system disorders
Drowsiness; Post-injection 1	74/308 (24%)	74	73/312 (23.4%)	73
Psychiatric disorders
Crying abnormal; Post-injection 1	112/308 (36.4%)	112	120/312 (38.5%)	120
Irritability; Post-injection 1	145/308 (47.1%)	145	142/312 (45.5%)	142

Limitations/Caveats

[Not Specified]

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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.