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Study of Yellow Fever Vaccine Administered With Tetravalent Dengue Vaccine in Healthy Toddlers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT01436396
First received: September 7, 2011
Last updated: April 1, 2014
Last verified: April 2014
  Purpose

The study is 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 in flavivirus (FV)-naïve subjects at baseline receiving one dose of Stamaril vaccine administered concomitantly with the first dose of CYD dengue vaccine compared to subjects receiving one dose of Stamaril vaccine concomitantly with placebo.

Secondary Objectives:

  • To assess the non-inferiority of yellow fever immune response 28 days post-Stamaril vaccination based on seroconversion rates regardless of the FV status of subjects at baseline.
  • 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.

Condition Intervention Phase
Dengue
Dengue Hemorrhagic Fever
Yellow Fever
Biological: Live, attenuated dengue serotype 1, 2, 3, and 4 virus
Biological: Yellow fever vaccine
Biological: Measles, mumps, and rubella vaccine
Biological: Pneumococcal Conjugated Vaccine
Biological: Hepatitis A Pediatric Vaccine
Biological: Diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae vaccine
Biological: Yellow Fever Vaccine
Biological: Placebo (NaCl)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Information on the antibody to yellow fever virus post Stamaril vaccination [ Time Frame: 28 days post-vaccination ] [ Designated as safety issue: No ]
    Yellow Fever antibodies will be determined by a yellow fever virus plaque reduction neutralization test (YF PRNT50) assay


Secondary Outcome Measures:
  • Information concerning the immunogenicity of CYD dengue vaccine post vaccination [ Time Frame: 28 days post-CYD dengue vaccination ] [ Designated as safety issue: No ]
    Dengue antibodies will be determined by a dengue virus plaque reduction neutralization test (PRNT50) assay

  • Information concerning the safety in terms of solicited injection site and systemic reactions, unsolicited adverse events, and serious adverse events post-vaccination with yellow fever and CYD dengue vaccines [ Time Frame: Day 0 up to 6 months post-final vaccination ] [ Designated as safety issue: No ]
    Solicited injection site reactions: Tenderness, Erythema, and Swelling; Solicited Systemic Reactions: Fever (temperature), Vomiting, Abnormal crying, Drowsiness, Loss of appetite, and Irritability


Enrollment: 792
Study Start Date: September 2011
Study Completion Date: March 2014
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CYD Dengue Vaccine Group 1
Participants will receive Stamaril® + CYD dengue vaccine dose 1 at age 12 to 13 months; measles, mumps, and rubella vaccine + pneumococcal conjugated vaccine + hepatitis A vaccine at 13 to 14 months; CYD dengue vaccine dose 2 at 18 to 19 months; DTaP IPV/Hib vaccine at 19 to 20 months; and CYD dengue vaccine dose 3 at 24 to 25 months.
Biological: Live, attenuated dengue serotype 1, 2, 3, and 4 virus
0.5 mL, subcutaneous at age 12, 18, and 24 months
Other Name: CYD Dengue Vaccine
Biological: Yellow fever vaccine
0.5 mL subcutaneous in the deltoid at age 12 to 13 months.
Other Name: Stamaril®
Biological: Measles, mumps, and rubella vaccine
0.5 mL, subcutaneous at age 12 to 13 months.
Other Name: MMR vaccine
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
Biological: Diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae vaccine
0.5 mL, intramuscular at age 19 to 20 months
Other Name: DTaP IPV//Hib Vaccine
Experimental: CYD Dengue Vaccine Group 2
Participants will receive Stamaril + placebo at age 12 to 13 months; measles, mumps, and rubella vaccine + pneumococcal conjugate vaccine + hepatitis A vaccine at 13 to 14 months; CYD dengue vaccine dose 1 at 18 to 19 months; DTaP IPV/Hib vaccine at 19 to 20 months; and CYD dengue vaccine dose 2 at 24 to 25 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 Name: CYD dengue vaccine
Biological: Yellow Fever Vaccine
0.5 mL, subcutaneous at age 12 to 13 months
Other Name: Stamaril®
Biological: Placebo (NaCl)
0.5 mL, subcutaneous at age 12 to 13 months
Other Name: NaCl 0.9%
Biological: Measles, mumps, and rubella vaccine
0.5 mL, subcutaneous at age 13 to 14 months
Other Name: MMR vaccine
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 Name: DTaP IPV//Hib Vaccine

Detailed Description:

All participants will receive a total of 8 injections during the study. Vaccine immunogenicity assessments for dengue neutralizing antibodies will be performed in a randomized subset of participants. All participants will be followed-up for safety during the study and for 6 months after the last CYD dengue vaccination.

  Eligibility

Ages Eligible for Study:   12 Months to 13 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  • Subject in good health, based on medical history and physical examination.
  • Subject has completed his/her vaccination schedule according to the official immunization calendar of Colombia and/or Peru, respectively.
  • Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative (and by 2 independent witnesses if required by local regulations).
  • Subject 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 yellow fever (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 will be 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 DTP 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01436396

Locations
Colombia
Cali, Colombia
Peru
Lima, Peru
Sponsors and Collaborators
Sanofi Pasteur, a Sanofi Company
Investigators
Study Director: Medical Director Sanofi Pasteur Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT01436396     History of Changes
Other Study ID Numbers: CYD29, U1111-1116-4913
Study First Received: September 7, 2011
Last Updated: April 1, 2014
Health Authority: Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Peru: INS Instituto Nacional de Salud, Oficina General de Investigación y Transferencia Tecnológica

Keywords provided by Sanofi:
Dengue
Dengue Hemorrhagic Fever
CYD Dengue Vaccines
Yellow Fever
Stamaril®
Flavivirus Infections

Additional relevant MeSH terms:
Dengue
Fever
Hemorrhagic Fevers, Viral
Severe Dengue
Yellow Fever
Arbovirus Infections
Body Temperature Changes
Flaviviridae Infections
Flavivirus Infections
RNA Virus Infections
Signs and Symptoms
Virus Diseases

ClinicalTrials.gov processed this record on November 23, 2014