Safety and Immunogenicity of Three Formulations of Takeda's Tetravalent Dengue Vaccine Candidate (TDV)

A Randomized, Double Blind, Phase 2 Study to Assess the Safety and Immunogenicity of Three Formulations of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Healthy Adults

The purpose of this study is to evaluate the equivalence of the lyophilized formulation of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) compared with the liquid formulation of TDV.

The vaccine being tested in this study is Takeda's Tetravalent Dengue Vaccine Candidate (TDV). This study is designed to determine whether the lyophilized formulation provides equivalent safety and immunogenicity as the original liquid formulation. An exploratory analysis has been added for the purpose of understanding whether there is a manufacturing or formulation effect on the vaccine.

The study will enroll approximately 1000 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the four study groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

• Group A: TDV Liquid Formulation 1, subcutaneous (SC) injection on Day 1 and placebo (dummy) SC at Month 3 - this is a liquid that looks like the study drug but has no active ingredient
• Group B: TDV Liquid Formulation 1, SC injection Day 1 and Month 3
• Group C: TDV Liquid Formulation 2, SC injection Day 1 and Month 3
• Group D: TDV Lyophilized formulation SC injection Day 1 and Month 3

In order to keep the treatment arms undisclosed to the participant and the doctor, participants will receive a placebo injection at any study visit where TDV is not being administered (Month 3). Participants will be asked to record any adverse events that may be related to the vaccine or the injection in a diary card for 28 days after each vaccination.

This multi-center trial will be conducted in the United States. The overall time to participate in this study is up to 10 months. Participants will make 9 visits to the clinic including a final visit 1 month after last dose of study drug for a follow-up assessment. A follow up phone call will be done 6 months after the last dose to assess serious adverse events.

Inclusion Criteria:

1. Is aged 18 to 49 years, at the time of enrollment inclusive.
2. Individuals who are 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. Signs and dates a written, informed consent 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. Febrile illness (temperature ≥ 38°C or 100.4°F) or moderate or severe acute illness or infection at the time of enrollment. Trial entry should be delayed until the illness has improved.
2. 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. Individuals with history of substance or alcohol abuse within the past 6 months; c. Female participants who are pregnant or breastfeeding; d. 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); e. 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); 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 with body mass index (BMI) greater than or equal to 35.
9. Participants who received previous vaccination (in a clinical trial or with an approved product) against flaviviruses including dengue, yellow fever (YF), West Nile (WN), Japanese Encephalitis (JE), and St. Louis encephalitis.
10. Documented or suspected disease caused by dengue, JE, WN, YF virus, and/or St. Louis encephalitis.
11. History of travel to dengue endemic areas including the Caribbean, Mexico, Central America, South America or Southeast Asia during the 6 months prior to screening or planned travel to a dengue endemic area during the study period.
12. Clinically significant abnormality in the screening laboratory tests as judged by the Investigator.
13. History of recurring headaches or migraines (more frequent than once per week) or on prescription medication for treatment of recurring headaches or migraines.
14. Blood tests positive for antibodies to HIV-1/2, Hepatitis C and Hepatitis B surface antigen.