Efficacy and Safety of Dengue Vaccine in Healthy Children

NCT00842530 | Completed Phase 2 Results DMC

• 2 other identifiers: CYD232014-001710-25
• Study Type: interventional
• Target: 4,002
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the study was to assess the efficacy of CYD dengue vaccine after three injections in preventing symptomatic virologically-confirmed dengue (VCD) cases, regardless of the severity, due to any of the four serotypes in children aged 4 to 11 years at the time of inclusion. Secondary objectives included to assess:

• Vaccine efficacy against severe VCD cases
• Vaccine efficacy against VCD cases following at least two injections with CYD dengue vaccine
• Immune response to CYD dengue vaccine
• Safety profile of CYD dengue vaccine. Safety assessments include solicited reactions within 7 or 14 days after each injection, unsolicited adverse events within 28 days after each injection, and serious adverse events during the study period. Other objectives included:
• Vaccine efficacy against VCD cases following at least one injection with CYD dengue vaccine
• Vaccine efficacy against VCD cases due to each serotype
• Participants with clinical signs and symptoms for VCD

Conditions

Dengue Virus; Dengue Fever; Dengue Hemorrhagic Fever; Dengue Diseases

Keywords

Dengue virus; Dengue fever; Dengue hemorrhagic fever; Dengue diseases; Dengue vaccine

Outcome Measures

Primary Outcomes (1)

• Number of Symptomatic Virologically-Confirmed Dengue (VCD) Cases During the Active Phase Post-dose 3 Following Inj. With Either CYD Dengue Vaccine or a Placebo

  Symptomatic VCD cases were defined as acute febrile illness with fever lasting for at least 1 day (temperature \>= 37.5 degree Celsius (°C) measured at least twice with an interval of at least 4 hours), confirmed by reverse transcriptase-polymerase chain reaction and/or dengue non-structural protein-1 (NS1) enzyme-linked immunosorbent assay antigen test, and occurring more than 28 days after the third injection. Vaccine efficacy was reported as density incidence (cases/100 person-years at risk). Density incidence was defined as the number of VCD cases divided by the cumulative person-years at risk.

  28 days Post-Inj. 3 up to the end of Active Phase (up to 13 months Post-Inj. 3, i.e. up to 25 months)

Secondary Outcomes (7)

• Number of Severe VCD Cases During the Active Phase Post-dose 3 Following Inj. With Either CYD Dengue Vaccine or a Placebo

  28 days Post-Inj. 3 up to the end of Active Phase (up to 13 months Post-Inj. 3, i.e. up to 25 months)

• Number of Symptomatic VCD Cases During the Active Phase Following at Least Two Inj. With Either CYD Dengue Vaccine or a Placebo

  28 days Post-Inj. 2 up to Inj. 3, 28 days Post-Inj. 2 up to end of Active Phase ( up to 25 months)

• Geometric Mean Titers (GMTs) of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Inj. With Either CYD Dengue Vaccine or a Placebo

  Pre-Inj. 1, 2, and 3, 28 days Post-Inj. 1, 2 and 3 and 1 year Post-Inj. 3

• GMTs of Antibodies Against Each Serotype With the Parental Dengue Virus Strain in Dengue-Immune Participants Before and Following Inj. With Either CYD Dengue Vaccine or a Placebo

  Pre-Inj. 1, 2, and 3, 28 days Post-Inj. 1, 2 and 3 and 1 year Post-Inj. 3

• GMTs of Antibodies Against Each Serotype With the Parental Dengue Virus Strain in Dengue Non-Immune Participants Before and Following Inj. With Either CYD Dengue Vaccine or a Placebo

  Pre-Inj. 1, 2, and 3, 28 days Post-Inj. 1, 2 and 3 and 1 year Post-Inj. 3

Other Outcomes (4)

• Number of Symptomatic VCD Cases During the Active Phase Following at Least One Inj. With Either CYD Dengue Vaccine or a Placebo

  Day 0 (Post-Inj.) up to end of Active phase (up to 25 months); 28 days post-Inj. 1 up to end of Active phase (up to 25 months)

• Number of Participants With One VCD Episode During the Active Phase Due to Each Serotypes Following Inj. With Either CYD Dengue Vaccine or a Placebo

  After 28 days Post Inj. 3 up to the end of Active Phase (up to 25 months)

• Mean Number of Days for Clinical Signs and Symptoms (Fever, Clinical Syndrome and Hospitalization) of VCD During the Active Phase Following Inj. With Either CYD Dengue Vaccine or a Placebo

  Day 0 (Post-Inj.) up to end of Active Phase (up to 25 months)

Study Arms (2)

CYD Dengue Vaccine Group

EXPERIMENTAL

Participants (both Cohort 1 and 2) received 3 injections of the CYD Dengue vaccine, 1 injection each at 0, 6, and 12 months.

Biological: CYD Dengue Vaccine

Control Group

PLACEBO COMPARATOR

Participants (Cohort 1) received rabies vaccine at Month 0 and placebo at 6 and 12 months. Participants (Cohort 2) received placebo at 0, 6, and 12 months.

Biological: Inactivated rabies virus vaccine; Biological: Placebo

Interventions

CYD Dengue Vaccine BIOLOGICAL

0.5 mL, Subcutaneous

Also known as: Dengvaxia

CYD Dengue Vaccine Group

Inactivated rabies virus vaccine BIOLOGICAL

0.5 mL, Subcutaneous

Also known as: Verorab®

Control Group

Placebo BIOLOGICAL

Sodium chloride 0.9%

Control Group

Eligibility Criteria

• Age: 4 Years - 11 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Participant in good health, based on medical history and physical examination.
• Provision of assent form signed by the participants (for participants \>= 7 years old) and informed consent form signed by the parent or another legally acceptable representative.
• Participant and parent/ legally acceptable representative able to attend all scheduled visits and to comply with all trial procedures.
• Participant attended one of the schools involved in the trial and living in the Ratchaburi Province.
• For a female participant of child-bearing potential (girls post-menarche), avoid becoming pregnant (use of an effective method of contraception or abstinence) for at least 4 weeks prior to first vaccination, until at least 4 weeks after the last vaccination.

You may not qualify if:

• Febrile illness (temperature \>= 37.5°C) or moderate or severe acute illness/infection on the day of vaccination, according to Investigator judgment.
• For a female participant of child-bearing potential (girls post-menarche), known pregnancy or positive urine pregnancy test on the day of the first trial vaccination.
• Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia.
• Planned participation in another clinical trial during the present trial period.
• Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy, or long-term systemic corticosteroids therapy.
• Known systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to the trial vaccines or to a vaccine containing any of the same substances.
• Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the Investigator.
• Receipt of blood or blood-derived products in the past 3 months.
• Participant deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent.
• Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination.
• Receipt of any vaccine in the 4 weeks preceding the first trial vaccination.
• Planned receipt of any vaccine in the 4 weeks following the first trial vaccination.e
• Participant who plans to attend another school (outside the trial area) or move to another city in the coming 30 months.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (1)

Sanofi Pasteur Investigational Site

Bangkok, 10400, Thailand

Location

Related Publications (6)

• Sabchareon A, Wallace D, Lang J, Bouckenooghe A, Moureau A. Efficacy of tetravalent dengue vaccine in Thai schoolchildren - Authors' reply. Lancet. 2013 Mar 30;381(9872):1094-5. doi: 10.1016/S0140-6736(13)60755-2. No abstract available.

  PMID: 23540847 RESULT

• Forrat R, Dayan GH, DiazGranados CA, Bonaparte M, Laot T, Capeding MR, Sanchez L, Coronel DL, Reynales H, Chansinghakul D, Hadinegoro SRS, Perroud AP, Frago C, Zambrano B, Machabert T, Wu Y, Luedtke A, Price B, Vigne C, Haney O, Savarino SJ, Bouckenooghe A, Noriega F. Analysis of Hospitalized and Severe Dengue Cases Over the 6 years of Follow-up of the Tetravalent Dengue Vaccine (CYD-TDV) Efficacy Trials in Asia and Latin America. Clin Infect Dis. 2021 Sep 15;73(6):1003-1012. doi: 10.1093/cid/ciab288.

  PMID: 33822015 DERIVED

• Sridhar S, Luedtke A, Langevin E, Zhu M, Bonaparte M, Machabert T, Savarino S, Zambrano B, Moureau A, Khromava A, Moodie Z, Westling T, Mascarenas C, Frago C, Cortes M, Chansinghakul D, Noriega F, Bouckenooghe A, Chen J, Ng SP, Gilbert PB, Gurunathan S, DiazGranados CA. Effect of Dengue Serostatus on Dengue Vaccine Safety and Efficacy. N Engl J Med. 2018 Jul 26;379(4):327-340. doi: 10.1056/NEJMoa1800820. Epub 2018 Jun 13.

  PMID: 29897841 DERIVED

• Plennevaux E, Sabchareon A, Limkittikul K, Chanthavanich P, Sirivichayakul C, Moureau A, Boaz M, Wartel TA, Saville M, Bouckenooghe A. Detection of dengue cases by serological testing in a dengue vaccine efficacy trial: Utility for efficacy evaluation and impact of future vaccine introduction. Vaccine. 2016 May 23;34(24):2707-12. doi: 10.1016/j.vaccine.2016.04.028. Epub 2016 Apr 18.

  PMID: 27102820 DERIVED

• Hadinegoro SR, Arredondo-Garcia JL, Capeding MR, Deseda C, Chotpitayasunondh T, Dietze R, Muhammad Ismail HI, Reynales H, Limkittikul K, Rivera-Medina DM, Tran HN, Bouckenooghe A, Chansinghakul D, Cortes M, Fanouillere K, Forrat R, Frago C, Gailhardou S, Jackson N, Noriega F, Plennevaux E, Wartel TA, Zambrano B, Saville M; CYD-TDV Dengue Vaccine Working Group. Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease. N Engl J Med. 2015 Sep 24;373(13):1195-206. doi: 10.1056/NEJMoa1506223. Epub 2015 Jul 27.

  PMID: 26214039 DERIVED

• Sabchareon A, Wallace D, Sirivichayakul C, Limkittikul K, Chanthavanich P, Suvannadabba S, Jiwariyavej V, Dulyachai W, Pengsaa K, Wartel TA, Moureau A, Saville M, Bouckenooghe A, Viviani S, Tornieporth NG, Lang J. Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial. Lancet. 2012 Nov 3;380(9853):1559-67. doi: 10.1016/S0140-6736(12)61428-7. Epub 2012 Sep 11.

  PMID: 22975340 DERIVED

MeSH Terms

Conditions

Dengue; Severe Dengue

Interventions

Dengue Vaccines

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)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Medical Director
• Organization: Sanofi Pasteur

Contact-US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi Pasteur, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The observer-blind design was chosen since the products have different appearances and could be recognized. The person who performed vaccinations knew which product was administered while neither the participant nor the Investigator in charge of safety evaluation knew which product was injected. To maintain the blind and minimize the potential bias, the control group used the same route and schedule as the study vaccine.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2009
• First Posted: February 12, 2009
• Study Start: February 1, 2009
• Primary Completion: September 1, 2013
• Study Completion: February 1, 2014
• Last Updated: April 5, 2022
• Results First Posted: July 26, 2019

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

TH (1)