Date

2021-03-30

Protocol

Protocol changed

Item Changed

Exclusion criteria

Previous Version

1.Has febrile illness (temperature >38°C) or moderate or severe acute illness or infection at the time of randomization., 2.Has history of 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., 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.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). 8.Females of childbearing potential who are sexually active, and who refuse to use an, acceptable contraceptive method up to 6 weeks post-second vaccination., 9.Deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized involuntarily., 10.Current alcohol abuse or drug addiction that may interfere with the participant’s ability to comply with trial procedures., 11.Identified as an employee of the Investigator or trial center, with direct involvement in the proposed trial or other trials under the direction of that Investigator or trial center.

Next Version

1 Febrile illness (temperature ?38°C) or moderate or severe acute illness or infection at the time of randomization., 2 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 subject due to participation in the trial, including but not limited to: a. Known hypersensitivity or allergy to any of the vaccine components. b. Female subjects (post-menarche) who are pregnant or breastfeeding. c. Individuals with any serious chronic or progressive disease according to judgment of the Investigator (eg, 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 (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. Human immunodeficiency virus (HIV) infection or HIV-related disease. vi. Genetic immunodeficiency., 3.Receipt of 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.Participation 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. Previous participation in any clinical trial of a dengue candidate vaccine, or previous receipt of a dengue vaccine., 6. First degree relatives of individuals involved in trial conduct., 7. 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). a. 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. b. Acceptable birth control methods are defined as 1 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]). Other contraceptive methods may be considered in agreement with the Sponsor and will be approved by the appropriate ethics committee., 8. Females of childbearing potential who are sexually active, and who refuse to use an acceptable contraceptive method up to 6 weeks post-second vaccination., 9. Deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized involuntarily., 10. Current alcohol abuse or drug addiction that may interfere with the subject’s ability to comply with trial procedures., 11. Identified as an employee of the Investigator or trial center, with direct involvement in the proposed trial or other trials under the direction of that Investigator or trial center. There may be instances when individuals meet all entry criteria except one that relates to transient clinical circumstances (eg, temperature elevation or recent use of excluded medication or vaccine). Under these circumstances, a subject may be considered eligible for trial entry or first vaccination, as applicable, if the appropriate window for delay has passed, inclusion/exclusion criteria have been rechecked, and if the subject is confirmed to be eligible. Any subjects who are assigned to receive a booster dose of trial vaccines (TDV or placebo) will not qualify for entry into the booster phase of the trial if they meet any of the following criteria: Febrile illness (temperature ?38°C) or moderate or severe acute illness or infection at the time of enrollment in the booster phase of the trial. 2. History or any illness that, in the opinion of the Investigator, might interfere with the results of the booster phase of the trial or pose an additional risk to the subject due to participation in the booster phase of the trial, including but not limited to: a. Known hypersensitivity or allergy to any of the vaccine components. b. Female subjects (post-menarche) who are pregnant or breastfeeding. c. Individuals with any serious chronic or progressive disease according to judgment of the Investigator (eg, 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 1b (Month 0b) (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 1b (Month 0b). iii. Receipt of immunoglobulins and/or any blood products since Day 120 (Month 4) (ie, 30 days after the second dose of trial vaccine) or planned administration during the booster phase of the trial. iv. Receipt of immunostimulants within 60 days prior to Day 1b (Month 0b). v. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1b (Month 0b). vi. HIV infection or HIV-related disease. vii. Genetic immunodeficiency. 3. Receipt of any other vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to Day 1b (Month 0b) or planning to receive any vaccine within 28 days after Day 1b (Month 0b). 4. Participation in any clinical trial with another investigational product at any time during participation in this trial or intent to participate in another clinical trial at any time during the conduct of the booster phase of this trial. 5. Participation in any clinical trial of a dengue candidate vaccine other than the current trial, or receipt of a dengue vaccine other than the trial vaccine at any time during participation in this trial. 6. First degree relatives of individuals involved in trial conduct. 7. Females of childbearing potential who are sexually active, and who have not used any of the acceptable contraceptive methods as specified under the criteria for entry into the trial, for at least 2 months prior to Day 1b (Month 0b) (see also trial entry inclusion criteria #5). 8. Females of childbearing potential who are sexually active, and who refuse to use an acceptable contraceptive method up to 6 weeks post-booster vaccination. 9. Deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized involuntarily at any time during participation in this trial. 10. Current alcohol abuse or drug addiction that may interfere with the subject’s ability to comply with trial procedures for the booster phase of the trial. 11. Identified as an employee of the Investigator or trial center, with direct involvement in the present trial or other trials under the direction of that Investigator or trial center. There may be instances when individuals meet all entry criteria for the booster phase of the trial except one that relates to transient clinical circumstances (eg, temperature elevation or recent use of excluded medication or vaccine). Under these circumstances, a subject may be considered eligible for booster vaccination if the appropriate window for delay has passed, inclusion/exclusion criteria for the booster phase have been rechecked, and if the subject is confirmed to be eligible for participation in the booster phase of the trial.