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

NCT01411241 | Completed Phase 3 Results DMC

• 2 other identifiers: CYD33U1111-1115-6290
• Study Type: interventional
• Target: 720
• Locations: 1 country
• Sites: 4

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.

Conditions

Dengue; Dengue Hemorrhagic Fever

Keywords

Dengue; Dengue Hemorrhagic Fever; CYD Dengue Vaccines; Pentaxim™

Outcome Measures

Primary Outcomes (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

  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).

  28 days post-injection

Secondary Outcomes (8)

• 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 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

• 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

• 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

• 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

Study Arms (2)

CYD Dengue Vaccine Group 1

EXPERIMENTAL

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; Biological: DTaP IPV//Hib vaccine; Biological: Placebo; Biological: Measles, mumps, and rubella vaccine; Biological: Pneumococcal vaccine

CYD Dengue Vaccine Group 2

EXPERIMENTAL

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; Biological: DTaP IPV//Hib vaccine; Biological: Placebo; Biological: Measles, mumps, and rubella vaccine; Biological: Pneumococcal vaccine

Interventions

Live, attenuated, recombinant dengue serotype 1, 2, 3, and 4 virus BIOLOGICAL

0.5 mL, subcutaneous at age 9 to 12, 15 to 18 and 21 to 24 months.

Also known as: CYD Dengue Vaccine

CYD Dengue Vaccine Group 1

DTaP IPV//Hib vaccine BIOLOGICAL

0.5 mL, intramuscular

Also known as: Pentaxim™

CYD Dengue Vaccine Group 1

Placebo BIOLOGICAL

0.5 mL, subcutaneous

Also known as: NaCl

CYD Dengue Vaccine Group 1

Measles, mumps, and rubella vaccine BIOLOGICAL

0.5 mL, subcutaneous

Also known as: Trimovax®

CYD Dengue Vaccine Group 1

Pneumococcal vaccine BIOLOGICAL

0.5 mL, intramuscular

Also known as: Prevenar®

CYD Dengue Vaccine Group 1

Eligibility Criteria

• Age: 9 Months - 12 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (4)

Unknown Facility

Acapulco de Juárez, Guerrero, CP 39670, Mexico

Location

Unknown Facility

Guadalajara, Jalisco, CP 44280, Mexico

Location

Unknown Facility

Monterrey, Nuevo León, CP 64460, Mexico

Location

Unknown Facility

Mérida, Yucatán, CP 97000, Mexico

Location

Related Links

• Related Info

MeSH Terms

Conditions

Dengue; Severe Dengue

Interventions

Pentavac; Measles-Mumps-Rubella Vaccine; Pneumococcal Vaccines; Heptavalent Pneumococcal Conjugate Vaccine

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Intervention Hierarchy (Ancestors)

Vaccines, Combined; Vaccines; Biological Products; Complex Mixtures; Measles Vaccine; Viral Vaccines; Mumps Vaccine; Rubella Vaccine; Streptococcal Vaccines; Bacterial Vaccines

Results Point of Contact

• Title: Director
• Organization: Sanofi Pasteur

Contact-US@sanofi.com

Study Officials

• Medical Director

  Sanofi Pasteur SA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2011
• First Posted: August 8, 2011
• Study Start: July 18, 2011
• Primary Completion: February 4, 2014
• Study Completion: April 1, 2014
• Last Updated: March 25, 2022
• Results First Posted: July 29, 2019

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

ME (4)