Study of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Adacel® in Healthy Subjects

NCT02992418 | Terminated Phase 3 Results DMC FDA Drug

• 3 other identifiers: CYD66U1111-1161-32942019-003136-23
• Study Type: interventional
• Target: 688
• Locations: 1 country
• Sites: 4

Brief Summary

The aim of the study was to investigate the immunogenicity and safety of CYD dengue vaccine and Tetanus Toxoid (T), Reduced Diphtheria Toxoid (D) and Acellular Pertussis Vaccine Adsorbed (ap) (Tdap) vaccine when both vaccines were administered concomitantly or sequentially. Primary Objectives:

• To demonstrate the non-inferiority of the humoral immune response to the Tdap booster dose concomitantly administered with the first dose of CYD dengue vaccine as compared to sequential administration, measured 28 days after Tdap booster dose.
• To demonstrate the non-inferiority of the humoral immune response to the first dose of CYD dengue vaccine concomitantly administered with Tdap as compared to sequential administration, measured 28 days after the first dose of CYD dengue vaccine. Secondary Objectives:
• To demonstrate the non-inferiority of the humoral immune response of 3 doses of CYD dengue vaccine with the first dose concomitantly administered with Tdap as compared to sequential administration, measured 28 days after the third dose of CYD dengue vaccine.
• To describe the humoral immune response at baseline and 28 days after the first and third doses of CYD dengue vaccine, in each and any group.
• To describe the humoral immune response of Tdap vaccine at baseline and 28 days after concomitant administration with the first dose of CYD dengue vaccine as compared to the sequential administration, in each and any group.
• To describe the safety of the CYD dengue vaccine and of the Tdap booster dose after each and any injection in each group.

Conditions

Dengue Fever; Dengue Hemorrhagic Fever

Keywords

Dengue Fever; Dengue Hemorrhagic Fever; CYD Dengue Vaccine; Dengavaxia®

Outcome Measures

Primary Outcomes (3)

• Geometric Mean Concentrations (GMCs) of Antibodies Against Pertussis Antigens (Pertussis Toxoid, Filamentous Hemagglutinin, Pertactin, and Fimbriae 2+3) 28 Days After Dose of Tdap Vaccine in Previously Dengue Immune Participants

  GMCs against each pertussis antigens (pertussis toxoid \[PT\], filamentous hemagglutinin \[FHA\], pertactin \[PRN\], fimbriae types 2 and 3 \[FIM2+3\]) were assessed using an enzyme-linked immunosorbent assay (ELISA) method and were measured in ELISA unit/milliliter (EU/mL). Dengue immune participants at Baseline were defined as participants with titers \>=10 (1/dilution) for at least one serotype with the parental dengue virus strain.

  28 days after Tdap vaccination

• Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens 28 Days After the Dose of Tdap Vaccine in the Previously Dengue Immune Participants

  Seroprotection against diphtheria (Anti-D) and tetanus (Anti-T) antigens was performed by Micrometabolic Inhibition Test - Toxin Neutralization assay (MIT-TNA) and ELISA, respectively. Seroprotection was defined as anti-D and anti-T Ab concentration greater than 0.1 international units (IU)/mL. Dengue immune participants at Baseline were defined as participants with titers \>=10 (1/dilution) for at least one serotype with the parental dengue virus strain.

  28 days after Tdap vaccination

• Geometric Mean Titers (GMTs) of Antibodies Against Each Dengue Virus Serotype 28 Days After the First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants

  The GMTs against each of the four parenteral dengue virus serotypes (1, 2, 3 and 4) of CYD dengue vaccine were assessed using the 50% plaque reduction neutralization test (PRNT50) assay method. Dengue immune participants at Baseline were defined as participants with titers \>=10 (1/dilution) for at least one serotype with the parental dengue virus strain. Titers were measured in terms of 1/dilution.

  28 days after first CYD dengue vaccination

Secondary Outcomes (12)

• Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype at Baseline and 28 Days After the First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants

  Baseline (Pre-CYD vaccination 1) and 28 days after the first CYD dengue vaccination

• Percentage of Participants With Neutralizing Antibody Titers Against Each of the 4 Dengue Virus Serotypes of CYD at Baseline and 28 Days After First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants

  Baseline (Pre-CYD vaccination 1) and 28 days after the first CYD dengue vaccination

• Percentage of Participants With Neutralizing Antibody Titers Above Predefined Thresholds Against at Least 1, 2, 3, or 4 Serotypes of CYD at Baseline and 28 Days After the First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants

  Baseline (Pre-CYD vaccination 1) and 28 days after the first CYD dengue vaccination

• Geometric Mean Concentrations of Serum Antibodies Against Pertussis Antigens (Pertussis Toxoid, Filamentous Hemagglutinin, Pertactin, and Fimbriae 2+3) at Baseline and 28 Days After the Dose of Tdap Vaccine in the Previously Dengue Immune Participants

  Baseline (Pre-Tdap vaccination) and 28 days after the Tdap vaccination

• Percentage of Participants Achieving Serum Antibody (>=0.1 IU/mL) Against Diphtheria and Tetanus Antigens at Baseline and 28 Days After the Dose of Tdap Vaccine in the Previously Dengue Immune Participants

  Baseline (Pre-Tdap vaccination) and 28 days after the dose of Tdap vaccination

Study Arms (2)

Concomitant Administration Group

EXPERIMENTAL

Participants will be administered the first dose of CYD dengue vaccine concomitantly with a dose of Tdap vaccine.

Biological: CYD Dengue Vaccine; Biological: Tdap: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine adsorbed

Sequential Administration Group

EXPERIMENTAL

Participants will be administered the first dose of CYD dengue vaccine 28 days after a dose of Tdap vaccine.

Biological: CYD Dengue Vaccine; Biological: Tdap: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed

Interventions

CYD Dengue Vaccine BIOLOGICAL

0.5 milliliter (mL), Subcutaneous at Month 1, 7 and Month 13, respectively

Also known as: Dengvaxia®

Concomitant Administration Group; Sequential Administration Group

Tdap: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed BIOLOGICAL

0.5 mL, intramuscularly (IM) at Month 1.

Also known as: Adacel®

Concomitant Administration Group

Eligibility Criteria

• Age: 9 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participant in good health, based on medical history and physical examination.
• Informed consent form (ICF) or assent form was signed and dated by the participant (based on local regulations), and/or ICF was signed and dated by the parent(s) or another legally acceptable representative (and by an independent witness if required by local regulations).
• For participant aged 9 to 11 years: known (documented) receipt of at least 4 previous doses of diphtheria toxoid, tetanus toxoid and acellular pertussis-containing (DTaP) vaccines, with the last dose not within the last 5 years prior to enrolment.
• OR For participant aged at least 12 years: known (documented or self-reported) receipt of at least 3 previous doses of diphtheria toxoid, tetanus toxoid, and whole cell pertussis-containing (DTwP) vaccines, with the last dose not within the last 5 years prior to enrolment.
• Participant (or participant and parent\[s\]/legally acceptable representatives) was able to attend all scheduled visits and complied with all trial procedures.

You may not qualify if:

• Participant was pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be pre-menarche or post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 4 weeks after the last vaccination).
• Participation at the time of study enrollment (or in the 4 weeks preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure.
• Planned receipt of any vaccine in the 4 weeks following any trial vaccination.
• Previous vaccination against dengue disease with the trial CYD dengue vaccine.
• Receipt of immune globulins, 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 (including human immunodeficiency virus (HIV) infection with impaired immune function); or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroids therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
• A previous severe reaction to pertussis, diphtheria or tetanus vaccine including immediate anaphylaxis, encephalopathy within 7 days or seizure within 3 days of receiving the vaccine.
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances.
• Thrombocytopenia, contraindicating IM vaccination.
• Deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized involuntarily.
• Current alcohol abuse or drug addiction that, based on Investigator's judgment, may interfere with the participant's ability to comply with trial procedures.
• Chronic illness that, in the opinion of the Investigator, was at a stage where it might interfere with trial conduct or completion.
• Identified as an Investigator or employee of the Investigator with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.
• Self-reported HIV, Hepatitis B, or Hepatitis C infection.
• Personal history of Guillain-Barré syndrome.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (4)

Unknown Facility

City of Muntinlupa, Alabang, Philippines

Location

Unknown Facility

Manila, 1000, Philippines

Location

Unknown Facility

Quezon, Philippines

Location

Unknown Facility

Quezon City, Philippines

Location

Related Publications (1)

• Santos J, Montellano ME, Solante R, Perreras N, Meyer S, Toh ML, Zocchetti C, Vigne C, Mascarenas C. Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Tdap Vaccine: Randomized Phase IIIb Trial in Healthy Participants 9-60 Years of Age in the Philippines. Pediatr Infect Dis J. 2021 Sep 1;40(9):856-863. doi: 10.1097/INF.0000000000003220.

  PMID: 34117198 DERIVED

MeSH Terms

Conditions

Dengue; Severe Dengue

Interventions

Dengue Vaccines; adacel

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

Limitations and Caveats

Due to absence of response of competent authorities from The Philippines on protocol amendment, the study was prematurely terminated before injection of last dose (3rd dose) of the CYD dengue vaccine. Objectives related to 3rd dose were not assessed.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi Pasteur

Contact-US@sanofi.com

800-633-1610

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: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2016
• First Posted: December 14, 2016
• Study Start: December 19, 2016
• Primary Completion: December 10, 2019
• Study Completion: December 10, 2019
• Last Updated: March 25, 2022
• Results First Posted: August 27, 2020

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

PH (4)