Clinical trial NCT02302066: Safety and Immunogenicity of Different Schedules of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Healthy Participants
Official title: A Phase II, Double-Blind, Controlled Trial to Assess the Safety and Immunogenicity of Different Schedules of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Healthy Subjects Aged Between 2 and <18 Years and Living in Dengue Endemic Countries in Asia and Latin America
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dengue Fever
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2014-11-26
Enrollment: 1800
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the humoral immune responses to three different dose schedules of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) administered subcutaneously in healthy participants between 2 and \<18 years of age living in dengue endemic countries.

Detailed description: The vaccine tested in this study is Takeda's Tetravalent Dengue Vaccine Candidate (TDV) which was administered in 3 different dosing schedules to participants aged from 2 to 17 years resident in dengue endemic countries. This study looked at the titers of antibodies to dengue fever elicited in people who received TDV.

The study randomized 1800 healthy participants. Participants were randomly assigned to one of the four treatment groups in a 1:2:5:1 ratio-which remained undisclosed to the participant and study doctor during the study (unless there was an urgent medical need):

* Group 1 - TDV 0.5 mL subcutaneous (SC) injection Days 1 and 91
* Group 2 - TDV 0.5 mL SC injection Day 1
* Group 3 - TDV 0.5 mL SC injection Days 1 and 365
* Group 4 - Placebo (dummy SC) - this is a liquid that looks like the study drug but has no active ingredient

A total of 600 participants were planned to be randomly included in immunogenicity analyses (approximately 100 participants planned in each of Group 1 and Group 4, and 200 participants planned in each of Group 2 and Group 3).

In order to keep the treatment arms undisclosed to the participant and the doctor, participants received a placebo injection at any study visit where TDV was not being administered (Days 1 and/or 91 and/or 365).

Participants were asked to record any symptoms that may be related to the vaccine or the injection site in a diary card for 28 days after each vaccination.

This multi-center trial was conducted in Asia and Latin America. Participants were followed for 48 months with 10 protocol-scheduled visits for participants included in the planned immunogenicity subset of approximately 600 subjects and 7 protocol-scheduled visits for subjects not included in the immunogenicity subset.

Eligibility criteria: Inclusion Criteria:

1. Is aged 2 to \<18 years, at the time of enrolment.
2. Is in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs), and clinical judgment of the investigator.
3. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form (and assent form, where required) and any required privacy authorization prior to the initiation of any trial procedures, after the nature of the trial has been explained according to local regulatory requirements.
4. Can comply with trial procedures and are available for the duration of follow-up.

Exclusion Criteria:

1. Febrile illness (temperature ≥ 38°C or 100.4°F) or moderate or severe acute illness or infection at the time of enrolment. Trial entry should be delayed until the illness has improved.
2. Individuals with history or any illness that, in the opinion of the investigator, might interfere with the results of the trial or pose additional risk to the participants due to participation in the trial, including but not limited to: a. Known hypersensitivity or allergy to any of the vaccine components; b. Female participants who are pregnant or breastfeeding; c. Individuals with any serious chronic or progressive disease according to judgment of the investigator (e.g. neoplasm, insulin-dependent diabetes, cardiac, renal or hepatic disease, neurologic or seizure disorder or Guillain-Barré syndrome); d. Known or suspected impairment/alteration of immune function, including: i. Chronic use of oral steroids (Equivalent to 20 mg/day prednisone ≥ 12 weeks / ≥ 2 mg/kg body weight / day prednisone ≥ 2 weeks) within 60 days prior to Day 1 (use of inhaled, intranasal, or topical corticosteroids is allowed); ii. Receipt of parenteral steroids (Equivalent to 20 mg/day prednisone ≥ 12 weeks / ≥ 2 mg/kg body weight / day prednisone ≥ 2 weeks) within 60 days prior to Day 1; iii. Administration of immunoglobulins and/or any blood products within the three months preceding the first administration of the investigational vaccine or planned administration during the trial; iv. Receipt of immunostimulants within 60 days prior to Day 1; v. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months preceding (first) vaccination; vi. Human immunodeficiency virus (HIV) infection or HIV-related disease; vii. Genetic immunodeficiency.
3. Individuals who received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this trial or who are planning to receive any vaccine within 28 days of investigational vaccine administration.
4. Individuals participating in any clinical trial with another investigational product 30 days prior to first trial visit or intent to participate in another clinical trial at any time during the conduct of this trial.
5. Individuals who are first degree relatives of individuals involved in trial conduct.
6. If female of childbearing potential, sexually active, and has not used any of the "acceptable contraceptive methods" for at least 2 months prior to trial entry: a. Of childbearing potential is defined as status post onset of menarche and not meeting any of the following conditions: menopausal (for at least 2 years), bilateral tubal ligation (at least 1 year previously), bilateral oophorectomy (at least 1 year previously) or hysterectomy; b. Acceptable birth control methods are defined as one or more of the following: i. Hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring); ii. Barrier (condom with spermicide or diaphragm with spermicide) each and every time during intercourse; iii. Intrauterine device (IUD); iv. Monogamous relationship with vasectomized partner. Partner must have been vasectomized for at least six months prior to the participants' trial entry.
7. If female of childbearing potential, sexually active and refuses to use an "acceptable contraceptive method" through to 6 weeks after the last dose of investigational vaccine.
8. Individuals who participated in a previous dengue vaccine trial.

Primary outcomes:
measure: Geometric Mean Titers (GMTs) of Neutralizing Antibodies (Microneutralization Test [MNT50]) for Each of the Four DENV Serotypes for Participants in the Immunogenicity Subset
timeFrame: Up to Month 48
Secondary outcomes:
measure: Seropositivity Rates For Each of the 4 Dengue Serotypes for Participants in the Immunogenicity Subset
timeFrame: Months 1, 3, 6, 12, 13, 18, 24, 36, and 48
measure: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary Recorded) by Severity in the Immunogenicity Subset of Infant/Toddler Following Each Vaccination
timeFrame: Within 7 days after each vaccination
measure: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary Recorded) by Severity in the Immunogenicity Subset of Adult/Children Following Each Vaccination
timeFrame: Within 7 days after each vaccination
measure: Percentage of Participants With Solicited Systemic Adverse Events (AEs) (Diary Recorded) by Severity in the Immunogenicity Subset of Infant/Toddler Following Each Vaccination
timeFrame: Within 14 days after each vaccination
measure: Percentage of Participants With Solicited Systemic Adverse Events (AEs) (Diary Recorded) by Severity in the Immunogenicity Subset of Adult/Children Following Each Vaccination
timeFrame: Within 14 days after each vaccination
measure: Percentage of Participants With Any Unsolicited Adverse Events (AEs) in the Immunogenicity Subset Following Each Vaccination
timeFrame: Within 28 days after each vaccination
measure: Percentage of Participants With Serious Adverse Events (SAEs)
timeFrame: From first vaccination through end of study (Day 1460)
measure: Percentage of Participants With Febrile Episodes of Virologically Confirmed Dengue With Onset 30 Days Post-first Vaccination
timeFrame: From 30 days post-first vaccination through end of study (Day 1460)
Other outcomes:
Locations:
city: Santo Domingo
country: Dominican Republic
facility: Hospital Maternidad Nuestra Senora de la Altagracia
state: Distrito Nacional Santo Domingo
city: Ciudad de Panama
country: Panama
facility: Centro De Vacunacion Internacional, S.A.(CEVAXIN)
city: Dasmarinas
country: Philippines
facility: Dela Salle Health Sciences Institute
state: Cavite
Study officials:
affiliation: Takeda
name: Program Medical Director
role: STUDY_DIRECTOR
References:
citation: Tricou V, Gottardo R, Egan MA, Clement F, Leroux-Roels G, Saez-Llorens X, Borkowski A, Wallace D, Dean HJ. Characterization of the cell-mediated immune response to Takeda's live-attenuated tetravalent dengue vaccine in adolescents participating in a phase 2 randomized controlled trial conducted in a dengue-endemic setting. Vaccine. 2022 Feb 16;40(8):1143-1151. doi: 10.1016/j.vaccine.2022.01.016. Epub 2022 Jan 22.
citation: Tsuji I, Dominguez D, Egan MA, Dean HJ. Development of a Novel Assay to Assess the Avidity of Dengue Virus-Specific Antibodies Elicited in Response to a Tetravalent Dengue Vaccine. J Infect Dis. 2022 May 4;225(9):1533-1544. doi: 10.1093/infdis/jiab064.
citation: Tricou V, Saez-Llorens X, Yu D, Rivera L, Jimeno J, Villarreal AC, Dato E, Saldana de Suman O, Montenegro N, DeAntonio R, Mazara S, Vargas M, Mendoza D, Rauscher M, Brose M, Lefevre I, Tuboi S, Borkowski A, Wallace D. Safety and immunogenicity of a tetravalent dengue vaccine in children aged 2-17 years: a randomised, placebo-controlled, phase 2 trial. Lancet. 2020 May 2;395(10234):1434-1443. doi: 10.1016/S0140-6736(20)30556-0. Epub 2020 Mar 17.
citation: Saez-Llorens X, Tricou V, Yu D, Rivera L, Jimeno J, Villarreal AC, Dato E, Mazara S, Vargas M, Brose M, Rauscher M, Tuboi S, Borkowski A, Wallace D. Immunogenicity and safety of one versus two doses of tetravalent dengue vaccine in healthy children aged 2-17 years in Asia and Latin America: 18-month interim data from a phase 2, randomised, placebo-controlled study. Lancet Infect Dis. 2018 Feb;18(2):162-170. doi: 10.1016/S1473-3099(17)30632-1. Epub 2017 Nov 6.
citation: Saez-Llorens X, Tricou V, Yu D, Rivera L, Tuboi S, Garbes P, Borkowski A, Wallace D. Safety and immunogenicity of one versus two doses of Takeda's tetravalent dengue vaccine in children in Asia and Latin America: interim results from a phase 2, randomised, placebo-controlled study. Lancet Infect Dis. 2017 Jun;17(6):615-625. doi: 10.1016/S1473-3099(17)30166-4. Epub 2017 Mar 30.