Clinical trial NCT02425098: Safety and Immunogenicity With Two Different Serotype 2 Potencies of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Adults in Singapore
Official title: A Phase II, Double-Blind, Randomized, Controlled Trial to Assess the Safety and Immunogenicity of a Tetravalent Dengue Vaccine With Two Different Serotype 2 Potencies in an Adult Population in Singapore
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dengue Fever
Keywords: Vaccine
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-04-23
Enrollment: 351
Sex: ALL
Minimum age (years): 21
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the post-vaccination neutralizing antibody response against each dengue serotype by vaccine group.

Detailed description: The vaccine being tested in this study was Takeda's Tetravalent Dengue Vaccine Candidate (TDV). TDV is being tested to protect people against dengue fever. This study looked at safety and the titers of antibodies to dengue fever induced in people who were administered a high-dose of TDV (HD-TDV) compared to TDV.

The study enrolled 351 patients. Before being assigned to a treatment group participants were screened for previous exposure to the dengue virus using a Dengue immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA). Participants were randomly assigned in 1:1 ratio (by chance) to one of the two treatment groups-which remained undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

* HD-TDV 0.5 mL subcutaneous injection
* TDV 0.5 mL subcutaneous injection

All participants received a single injection on Day 1. Participants were asked to record any symptoms that may or may not be related to the vaccine or the injection site in a diary card for 28 days after vaccination.

This multi-center trial was conducted in Singapore. The overall time of participation in this study was 12 months. Participants made multiple visits to the clinic, including a final visit 1 year after receiving their dose of TDV.

Eligibility criteria: Inclusion Criteria:

1. Participant signs and dates a written informed consent form where applicable, 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.
2. Is aged 21 to 45 years of age, inclusive.
3. 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.
4. Can comply with trial procedures and are available for the duration of follow-up.
5. Has self-declared as never having been vaccinated against Yellow Fever or Japanese Encephalitis Virus.

Exclusion Criteria:

1. Has febrile illness (temperature ≥38°C or ≥100.4°F) or moderate or severe acute illness or infection at the time of enrollment.
2. Has history or any illness that, in the opinion of the Investigator, might interfere with the results of the trial or pose an additional risk to the participant due to participation in the trial, including but not limited to:

   1. Known hypersensitivity or allergy to any of the vaccine components.
   2. Female participants who are pregnant or breastfeeding.
   3. 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).
   4. 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 (Month 0) (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 (Month 0).
      * iii. Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (Month 0) or planned administration during the trial.
      * iv. Receipt of immunostimulants within 60 days prior to Day 1(Month 0).
      * v. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1 (Month 0).
      * vi. Human immunodeficiency virus (HIV) infection and HIV-related diseases.
      * vii. Hepatitis C virus (HCV) infection.
      * viii. Genetic immunodeficiency.
3. Has received any other vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to Day 1 (Month 0) or planning to receive any vaccine within 28 days after Day 1 (Month 0).
4. Has participated in any clinical trial with another investigational product 30 days prior to Day 1 (Month 0) or intent to participate in another clinical trial at any time during the conduct of this trial.
5. Has previously participated in any clinical trial of a dengue candidate vaccine, or previous receipt of a dengue vaccine.
6. Is first-degree relative of individuals involved in trial conduct.
7. For 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 (Month 0).

   1. Of childbearing potential is defined as status post onset of menarche and not meeting any of the following conditions: bilateral tubal ligation (at least 1 year previously), bilateral oophorectomy (at least 1 year previously) or hysterectomy.
   2. 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 Day 1 \[Month 0\]).
8. Females of childbearing potential who are sexually active, and who refuse to use an acceptable contraceptive method from signing the informed consent up to 6 weeks post-vaccination.

Primary outcomes:
measure: Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 15
timeFrame: Day 15
measure: Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 30
timeFrame: Day 30
measure: Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 90
timeFrame: Day 90
measure: Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 180
timeFrame: Day 180
measure: Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 365
timeFrame: Day 365
measure: Seropositivity Rate for Each of the Four Dengue Serotypes at Day 15
timeFrame: Day 15
measure: Seropositivity Rate for Each of the Four Dengue Serotypes at Day 30
timeFrame: Day 30
measure: Seropositivity Rate for Each of the Four Dengue Serotypes at Day 90
timeFrame: Day 90
measure: Seropositivity Rate for Each of the Four Dengue Serotypes at Day 180
timeFrame: Day 180
measure: Seropositivity Rate for Each of the Four Dengue Serotypes at Day 365
timeFrame: Day 365
Secondary outcomes:
measure: Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary Recorded) Following Vaccination by Severity
timeFrame: Within 7 days after Vaccination
measure: Number of Participants With Solicited Systemic Adverse Events (AEs) (Diary Recorded) Following Vaccination by Severity
timeFrame: Within 14 days after Vaccination
measure: Number of Participants With at Least One Unsolicited Adverse Events (AEs) Following Vaccination
timeFrame: Within 28 days after Vaccination
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From first vaccination through end of study (Day 365)
measure: Geometric Mean Neutralizing Antibody Titers (GMT) for Each of the Four Dengue Serotypes Assessed by Dengue Baseline Seropositivity (MNT) Status
timeFrame: Days 15, 30, 90, 180 and 365
measure: Seropositivity Rate for Each of the Four Dengue Serotypes Assessed by Dengue Baseline Seropositivity (MNT) Status
timeFrame: Days 15, 30, 90, 180, and 365
measure: Percentage of Participants Positive for Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination
timeFrame: Days 5, 7, 9, 11, 15, 17, 21 and 30
measure: Duration of Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination
timeFrame: Days 5, 7, 9, 11, 15, 17, 21 and 30
measure: Level of Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination
timeFrame: Days 5, 7, 9, 11, 15, 17, 21 and 30
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: Singapore
country: Singapore
facility: Changi General Hospital
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: White LJ, Young EF, Stoops MJ, Henein SR, Adams EC, Baric RS, de Silva AM. Defining levels of dengue virus serotype-specific neutralizing antibodies induced by a live attenuated tetravalent dengue vaccine (TAK-003). PLoS Negl Trop Dis. 2021 Mar 12;15(3):e0009258. doi: 10.1371/journal.pntd.0009258. eCollection 2021 Mar.
citation: Michlmayr D, Andrade P, Nascimento EJM, Parker A, Narvekar P, Dean HJ, Harris E. Characterization of the Type-Specific and Cross-Reactive B-Cell Responses Elicited by a Live-Attenuated Tetravalent Dengue Vaccine. J Infect Dis. 2021 Feb 3;223(2):247-257. doi: 10.1093/infdis/jiaa346.
citation: Tricou V, Low JG, Oh HM, Leo YS, Kalimuddin S, Wijaya L, Pang J, Ling LM, Lee TH, Brose M, Hutagalung Y, Rauscher M, Borkowski A, Wallace D. Safety and immunogenicity of a single dose of a tetravalent dengue vaccine with two different serotype-2 potencies in adults in Singapore: A phase 2, double-blind, randomised, controlled trial. Vaccine. 2020 Feb 5;38(6):1513-1519. doi: 10.1016/j.vaccine.2019.11.061. Epub 2019 Dec 13.