| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Healthy volunteers (Hepatitis B Virus infection) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Hepatitis B virus (HBV) infection, especially chronic infection, is a significant worldwide medical problem that affects the liver |
|
| 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 | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10019731 |
| E.1.2 | Term | Hepatitis B |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 evaluate the reactogenicity and safety in all study groups. |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the humoral immune response in all study groups. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
-Participants who the investigator believe can and will comply with the requirements of the protocol. INC#1
-Written informed consent obtained from the participant prior to performance of any study-specific procedure. INC#2
-Healthy participants as established by medical history, clinical examination and clinical laboratory assessment before entering the study. INC#3
-A male or female between, and including, 18 and 45 years at the time of the first study intervention administration. INC#4
-Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause. INC#5
-Female participants of childbearing potential may be enrolled in the
study, if the participant: INC#6
•has practiced adequate contraception for 1 month prior to study intervention administration, and
•has a negative pregnancy test on the day of study intervention administration, and
•has agreed to continue adequate contraception during the entire
treatment period and for at least 3 months after completion of the study intervention administration series.
•blood sample for simultaneous follicle-stimulating hormone (FSH) and estradiol levels may be collected at the discretion of the investigator to confirm non-reproductive potential according to local laboratory reference range.
|
|
| E.4 | Principal exclusion criteria |
Medical conditions
-Previous vaccination against Hepatitis B. EXC#1
-Positive for anti-HBs antibodies or anti-HBc antibodies or HBsAg. EXC#2
-Any previous administration of monophosphoryl lipid (MPL) and/or
AS37. EXC#3
-Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. EXC#4
-Any confirmed or suspected autoimmune disease. EXC#5
-History of any reaction or hypersensitivity likely to be exacerbated by
any component of the study intervention(s). EXC#6
-Recurrent history or uncontrolled neurological disorders or seizures. EXC#7
-Any other clinical condition that, in the opinion of the investigator,
might pose additional risk to the participant due to participation in the study. EXC#8
-Any clinically significant* haematological and/or biochemical laboratory abnormality. EXC#9
*The investigator should use his/her clinical judgement to decide which abnormalities are clinically significant.
-Any past or current malignancies and lymphoproliferative disorders.
EXC#10
Prior/Concomitant therapy
-Use of any investigational or non-registered product (drug or vaccine) other than the study intervention(s) during the period beginning 30 days before the first dose of study intervention(s) or their planned use during the study period. EXC#11
-Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before each dose and ending 30 days after each dose of study intervention(s) administration with the exception of influenza vaccine (pandemic or seasonal). EXC#12
-A vaccine not foreseen by the study protocol administered during the period starting at Visit 1 or 30 days before each dose and ending 30 days after the last dose of study intervention(s) administration*, with the exception of influenza vaccine (pandemic or seasonal). EXC#13
*In case emergency mass vaccination for an unforeseen public health
threat (e.g. a pandemic) is organised by public health authorities outside the routine immunisation programme, the time period described above can be reduced if necessary for that vaccine, provided it is licensed/authorised and used according to its Product Information.
-Administration of long-acting immune-modifying drugs at any time
during the study period. EXC#14
-Chronic administration (defined as more than 14 days in total) of
immunosuppressants or other immune-modifying drugs during the
period starting 3 months before the first study intervention dose(s). For corticosteroids, this will mean prednisone equivalent ≥20 mg/day for adult participants/ ≥0.5 mg/kg/day. Inhaled and topical steroids are allowed. EXC#15
-Administration of immunoglobulins and/or any blood products or
plasma derivatives during the period starting 3 months before the
administration of the first dose of study intervention(s) or planned
administration during the study period. EXC#16
Prior/Concurrent clinical study experience
-Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational intervention. EXC#17
Other exclusions
-Pregnant or lactating female. EXC#18
-Female planning to become pregnant or planning to discontinue contraceptive precautions. EXC#19
-History of chronic alcohol consumption and/or drug abuse. EXC#20
-Any study personnel or their immediate dependants, family, or
household members. EXC#21
Specific exclusion for MRI-assessable subgroup participants (postrandomization procedure)
-Exclusions identified on local radiology department pre-MRI checklist. EXC#22
-Claustrophobia. EXC#23
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Percentage of participants with solicited administration site events
2. Percentage of participants with solicited administration site events
3. Percentage of participants with solicited systemic events
4. Percentage of participants with solicited systemic events
5. Duration of solicited administration site events
6. Duration of solicited administration site events
7. Duration of solicited systemic events
8. Duration of solicited systemic events
9. Percentage of participants with any unsolicited adverse events (AEs)
10. Percentage of participants with any unsolicited adverse events (AEs)
11. Percentage of participants with serious AEs (SAEs)
12. Percentage of participants with medically attended AEs (MAEs)
13. Percentage of participants with AEs leading to study withdrawal
14. Percentage of participants with potential mediated immune diseases (pIMDs)
15. Percentage of participants with changes from baseline (pre-vaccination, Day 1) in haematology and biochemistry parameters at Day 8
16. Percentage of participants with changes from baseline (pre-vaccination, Day 1) in haematology and biochemistry parameters at Day 31
17. Percentage of participants with changes from baseline (pre-vaccination, Day 1) in haematology and biochemistry parameters at Day 38
18. Percentage of participants with changes from baseline (pre-vaccination, Day 1) in haematology and biochemistry parameters at Day 61
19. Percentage of participants with abnormal haematology and biochemistry laboratory parameter values at Day 1
20. Percentage of participants with abnormal haematology and biochemistry laboratory parameter values at Day 8
21. Percentage of participants with abnormal haematology and biochemistry laboratory parameter values at Day 31
22. Percentage of participants with abnormal haematology and biochemistry laboratory parameter values at Day 38
23. Percentage of participants with abnormal haematology and biochemistry laboratory parameter values at Day 61 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1, 3, 5, 7, 9. Within 14 days after Dose 1 administration (Dose 1 administered at Day 1)
2, 4, 6, 8, 10. Within 14 days after Dose 2 administration (Dose 2 administered at Day 31)
11. Throughout the entire study period (from Day 1 to Day 361)
12. Throughout the entire study period (from Day 1 to Day 361)
13. Throughout the entire study period (from Day 1 to Day 361)
14. Throughout the entire study period (from Day 1 to Day 361)
15. At baseline (pre-vaccination, Day 1) and at Day 8
16. At baseline (pre-vaccination, Day 1) and at Day 31
17. At baseline (pre-vaccination, Day 1) and at Day 38
18. At baseline (pre-vaccination, Day 1) and at Day 61
19. At Day 1
20. At Day 8
21. At Day 31
22. At Day 38
23. At Day 61 |
|
| E.5.2 | Secondary end point(s) |
1. Anti-HBs antibody concentrations
2. Percentage of participants seroconverted for anti-HBs
3. Percentage of participants seroprotected for anti-HBs
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, At Day 1, Day 31, Day 61 and Day 361
2, 3, At Day 31, Day 61 and Day 361
|
|
| 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 |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| 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 | Yes |
| 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 | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 4 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| United Kingdom |
| Belgium |
| Germany |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
| End of Study (EoS): Date of the Last Subject Last Visit (LSLV). |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | 25 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 25 |
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