E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Assessment of how different dosing schedules of the vaccine effect immunity to dengue fever in dengue endemic countries. |
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E.1.1.1 | Medical condition in easily understood language |
Dengue fever is caused by infection with dengue virus, a RNA virus that occurs as 4 recognized serotypes: DENV-1, -2, -3, or -4. These viruses are transmitted from human to human by mosquitoes. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012312 |
E.1.2 | Term | Dengue fever virus infection |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the humoral immune responses to subcutaneously administered TDV in a subset of healthy subjects aged between 2 and <18 years and living in dengue endemic countries. |
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E.2.2 | Secondary objectives of the trial |
Immunogenicity: To assess seropositivity rates following subcutaneously administered TDV in a subset of healthy subjects aged between 2 and <18 years and living in dengue endemic countries.
Safety: To evaluate the safety of subcutaneously administered TDV in healthy subjects aged between 2 and <18 years and living in dengue endemic countries. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The subject is aged 2 to <18 years, at the time of enrollment 2. Individuals 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. The subject or, when applicable, the subject’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. Individuals can comply with trial procedures and are available for the duration of follow-up. |
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E.4 | Principal 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.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-BarreĢ 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 participated in a previous dengue vaccine trial. 6.Individuals who are first degree relatives of individuals involved in trial conduct. 7.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. v. Sexual abstinence agreement 8.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.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Geometric Mean Titers (GMTs) of neutralizing antibodies (microneutralization test [MNT50]) for each of the four DENV Serotypes |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Months 1, 3, 6, 12, 13, 18, 24, 36, and 48 |
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E.5.2 | Secondary end point(s) |
Immunogenicity: 1. Seropositivity rates (%)for each of the four DENV serotypes where seropositivity (MNT50) is defined as a reciprocal neutralizing titer ≥ 10 at Months 1, 3, 6, 12, 13, 18, 24, 36, and 48.
Safety: Immunogenicity subset: 1. Frequency and severity of solicited local (injection site) and systemic AEs for 7 and 14 days after each vaccination, respectively. 2. Percentage of subjects with any unsolicited AEs for 28 days after each vaccination.
All Subjects: 1.Percentage of subjects with SAEs throughout the trial. 2.Percentage of subjects with febrile episodes of virologically confirmed dengue throughout the trial. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Multiple time points occurring as stated in Section E.5.2 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Dominican Republic |
Panama |
Philippines |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |