| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Healthy Volunteers
"Vaccination against Dengue Fever and co-administration with Hepatitis A vaccine" |
|
| 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. |
|
| 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 |
|
| 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 demonstrate NI of the immune response to 1 dose of HAV vaccine in HAV/DENV-naive subjects 1 month following co-administration with 1 dose of TDV (Group 3) compared to 1 dose of HAV vaccine co-administered with placebo (Group 1). |
|
| E.2.2 | Secondary objectives of the trial |
Immunogenicity
-To describe the immune response to TDV in HAV/DENV-naive subjects 1 month following a second dose of TDV given 3 months after a first dose of TDV co-administered with HAV
vaccine (Group 3) or placebo (Group 2).
- To describe the immune response to TDV in HAV/DENV-naive subjects 1 month following a first dose of TDV co-administered with HAV vaccine (Group 3) or placebo (Group 2).
- To describe the immune response to the HAV vaccine in HAV/DENV-naive subjects 1 month following 1 dose of HAV vaccine co-administered with TDV (Group 3) or placebo
(Group 1).
Safety
- To assess the safety profile after each vaccine injection in Groups 1, 2 and 3. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. The subject is aged 18 to 60 years, 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. The subject 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. Assent is obtained from the subject where required.
4. Individuals who can comply with trial procedures and are available for the duration of follow-up. |
|
| E.4 | Principal exclusion criteria |
1. Individuals with an elevated oral temperature (≥38°C or 100.4°F) within 3 days of the intended date of vaccination (consider whether applicable as an exclusion criterion or criterion for delay.
2. Known hypersensitivity or allergy to any of the vaccine components (including excipients of the investigational vaccines or placebo).
3. Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the Investigator, may interfere with the subject’s ability to participate in the trial.
4. Individuals with any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (eg, Guillain-Barré syndrome).
5. 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 subject due to participation in the trial.
6. Known or suspected impairment/alteration of immune function, including:
a. 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).
b. 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).
c. Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (M0) or planned administration during the trial.
d. Receipt of immunostimulants within 60 days prior to Day 1(M0).
e. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1 (M0).
f. Human immunodeficiency virus (HIV) infection or HIV-related disease.
g. HAV infection.
h. Hepatitis C virus infection.
i. Genetic immunodeficiency.
7. Abnormalities of splenic or thymic function.
8. Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
9. Individuals with any serious chronic or progressive disease according to judgment of the Investigator (eg, neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).
10. Individuals with body mass index (BMI) greater than or equal to 35 kg/m2 (=weight in kg/[height in meters2]).
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. Individuals who 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. Previous HAV vaccination (in a clinical trial or with an approved product).
14. Individuals involved in the trial conduct or their first degree relatives.
15. Individuals with history of substance or alcohol abuse within the past 2 years.
16. Female subjects who are pregnant or breastfeeding.
17. 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).
18. 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 (Day 90 [M3]). In addition, they must be advised not to donate ova during this period.
19. Any positive or indeterminate pregnancy test.
20. Previous and planned vaccination (during the trial conduct) against any flaviviruses including dengue, yellow fever (YF), Japanese Encephalitis (JE) viruses or tick-borne encephalitis.
21. Previous participation in any clinical trial of a dengue or other flavivirus (eg, West Nile [WN] virus) candidate vaccine, except for subjects who received placebo in those trials.
22. Subjects with a current or previous infection witha flavivirus such as dengue, Zika, YF, JE, WN fever, tick-borne encephalitis or Murray Valley encephalitis and subjects with a history of prolonged (≥1 year) habitation in a dengue endemic area.
23. Individuals with contraindications, warnings and/or precautions to vaccination with the HAV vaccine as specified within the product information.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Proportion of subjects HAV/DENV-naive at Baseline who are seroprotected against HAV at Day 30 (Month 1 [M1]) as measured by enzyme-linked immunosorbent assay (ELISA) (seroprotection rate) in a subset of 120 subjects in each group (immunogenicity subset). Seroprotection is defined as serum anti-HAV antibody levels ≥10 mIU/mL.
Immunological naivety to HAV/DENV is defined as anti-HAV antibody levels <10 mIU/mL and reciprocal neutralizing titers for all 4 dengue serotypes <10. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Immunogenicity (immunogenicity subset):
- Geometric mean titers (GMT) of neutralizing antibodies (microneutralization test [MNT50]) for each of the 4 dengue serotypes at Day 30 (M1) and Day 120 (Month 4 [M4]) in subjects HAV/DENV-naive at Baseline.
Proportion of subjects HAV/DENV-naive at Baseline who are seropositive for each of the 4 dengue serotypes at Day 30 (M1) and Day 120 (M4) (seropositivity rate). Seropositivity is defined as a reciprocal neutralizing titer ≥10.
- Geometric mean concentrations (GMC) of anti-HAV antibodies on Day 30 (M1) in subjects HAV/DENV-naive at Baseline.
Safety (all subjects):
- Frequency and severity of solicited local (injection site[s]) adverse events (AE) for 7 days (day of vaccination + 6 subsequent days) and solicited systemic AEs for 14 days (day of
vaccination + 13 subsequent days) after each trial vaccination.
- Percentage of subjects with any unsolicited AEs for 28 days (day of vaccination + 27 subsequent days) after each trial vaccination.
- Percentage of subjects with serious adverse events (SAE) throughout the trial.
- Percentage of subjects with medically attended adverse events (MAAE) throughout the trial. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Immunogenicity:
Day 30 (M1) and Day 120 (Month 4 [M4])
Safety:
Throughout the trial |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| 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 | No |
| 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 |
|
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | No |
| 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 |
|
| 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 | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
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