Clinical trial NCT03341637: Immunogenicity and Safety of Tetravalent Dengue Vaccine (TDV) in Adolescents in Non-Endemic Area(s)
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Investigate the Immunogenicity and Safety of Subcutaneous Administration of a Tetravalent Dengue Vaccine Candidate in Healthy Adolescent Subjects in Non-Endemic Area(s) for Dengue
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dengue
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2017-11-14
Enrollment: 400
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to describe the neutralizing antibody response against each dengue serotype at 1 month post second dose of TDV or placebo in dengue-naive adolescent participants.

Detailed description: The vaccine tested in this study was tetravalent dengue vaccine (TDV). TDV was tested to assess the safety and immunogenicity in healthy adolescents in non-endemic area(s) for dengue.

The study enrolled 400 healthy participants. Participants were randomized in 3:1 ratio to receive:

* TDV 0.5 mL subcutaneous injection
* Placebo normal saline solution (0.9% NaCl) for injection.

In each trial group, participants received 2-dose schedule of TDV or placebo by subcutaneous injection on Days 1 (Month 0) and 90 (Month 3), but not all participants received both doses (8 subjects discontinued the trial before receiving the second dose).

This multi-center trial was conducted in Mexico. The overall time to participate in this study was 270 days. Participants had multiple visits to the clinic including a final visit at Day 270.

Eligibility criteria: Inclusion Criteria:

1. The participant is aged 12 to 17 years, inclusive;
2. Is in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and the clinical judgment of the Investigator.
3. The participant/the participant's legally authorized representative (LAR) signs and dates a written, informed consent/assent form 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. Individuals who can comply with trial procedures and are available for the duration of follow-up.

Exclusion Criteria:

1. Has an elevated oral temperature (≥38°C or 100.4°F) within 3 days of the intended date of vaccination.
2. Known hypersensitivity or allergy to any of the vaccine components.
3. Behavioral or cognitive impairment or psychiatric disease that, in the opinion of the Investigator, may interfere with the participant's ability to participate in the trial.
4. Has any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (e.g., Guillain-Barre syndrome).
5. 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 participant due to participation in the trial.
6. Has known or suspected impairment/alteration of immune function, including:

   1. 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 (M0) (use of inhaled, intranasal, or topical corticosteroids is allowed).
   2. 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 (M0).
   3. Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (M0) or planned administration during the trial.
   4. Receipt of immune-stimulants within 60 days prior to Day 1 (M0).
   5. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1 (M0).
   6. Human immunodeficiency virus (HIV) infection or HIV-related disease.
   7. Genetic immunodeficiency.
7. Has abnormalities of splenic or thymic function.
8. Has a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding.
9. Has any serious chronic or progressive disease according to judgment of the Investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).
10. Has body mass index (BMI) greater than or equal to 35 kg/m\^2 (= weight in kg/\[height in square meters\]).
11. Individuals participating in any clinical trial with another investigational product 30 days prior to Day 1 (M0) or intent to participate in another clinical trial at any time during the conduct of this trial.
12. Has received any other vaccine 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 trial vaccine administration.
13. Individuals involved in the trial conduct or their first degree relatives.
14. Has history of substance or alcohol abuse within the past 2 years.
15. Female participants who are pregnant or breastfeeding.
16. Females of childbearing potential who are sexually active, and who have not used any of the acceptable contraceptive methods for at least 2 months prior to Day 1 (M0).
17. Females of childbearing potential who are sexually active, and who refuse to use an acceptable contraceptive method up to 6 weeks after the last dose of trial vaccine. In addition, they must be advised not to donate ova during this period.
18. Any positive or indeterminate pregnancy test.
19. Previous and planned vaccination (during the trial conduct), against any flaviviruses including dengue, yellow fever (YF), Japanese encephalitis (JE) viruses or tick-borne encephalitis.
20. Previous participation in any clinical trial of a dengue or other flavivirus (eg, West Nile \[WN\] virus) candidate vaccine, except for participants who received placebo in those trials.
21. Participants with documented or suspected disease caused by a flavivirus such as dengue, Zika, YF, JE, WN fever, tick-borne encephalitis or Murray Valley encephalitis.

Primary outcomes:
measure: Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 120
timeFrame: One month post second dose (Day 120)
Secondary outcomes:
measure: Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 270
timeFrame: Six months post second dose (Day 270)
measure: Seropositivity Rates for Each of the 4 Dengue Serotypes
timeFrame: One month and six months post second dose (Day 120 and Day 270)
measure: Seropositivity Rates for Multiple (2, 3 or 4) Dengue Serotypes
timeFrame: One month and six months post second dose (Day 120 and Day 270)
measure: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary Recorded) Following Each Vaccination by Severity
timeFrame: Within 7 days after each vaccination
measure: Percentage of Participants With Solicited Systemic Adverse Events (AEs) (Diary Recorded) Following Each Vaccination by Severity
timeFrame: Within 14 days after each vaccination
measure: Percentage of Participants With Any Unsolicited Adverse Events (AEs) Following Each Vaccination
timeFrame: Within 28 days after each vaccination
measure: Percentage of Participants With Medically Attended AEs (MAAEs) Throughout the Study
timeFrame: From first vaccination (Day 1) through end of study (Day 270)
measure: Percentage of Participants With Serious Adverse Events (SAEs) Throughout the Study
timeFrame: From first vaccination (Day 1) through end of study (Day 270)
Other outcomes:
Locations:
city: Ciudad de Mexico
country: Mexico
facility: Biodextra, S.A. de C.V.
city: Mexico City
country: Mexico
facility: Instituto Nacional de Pediatria (INP)
city: Mexico City
country: Mexico
facility: Hospital Infantil de Mexico Federico Gomez
city: Mexico City
country: Mexico
facility: Mexico Centre for Clinical Research
city: Mexico City
country: Mexico
facility: Centro de Atencion E Investigacion Medica (CAIMED) Mexico DF
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: Biswal S, Mendez Galvan JF, Macias Parra M, Galan-Herrera JF, Carrascal Rodriguez MB, Rodriguez Bueno EP, Brose M, Rauscher M, LeFevre I, Wallace D, Borkowski A. Immunogenicity and safety of a tetravalent dengue vaccine in dengue-naive adolescents in Mexico City. Rev Panam Salud Publica. 2021 Jun 11;45:e67. doi: 10.26633/RPSP.2021.67. eCollection 2021.