E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatitis B vaccination in healthy adults |
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E.1.1.1 | Medical condition in easily understood language |
Hepatitis B vaccination in healthy adults |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054181 |
E.1.2 | Term | Hepatitis B immunization |
E.1.2 | System Organ Class | 100000004865 |
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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 demonstrate that the SPR 4 weeks after completion of the three-dose regimen of Sci-B-Vac™ is non-inferior to the SPR 4 weeks after completion of the three-dose regimen of Engerix-B® in adults ≥18 years of old i.e. the lower bound of the 95% two-sided confidence interval (CI) of the difference between the SPR in the Sci-B-Vac™ arm minus the SPR in the Engerix-B® arm, achieved 4 weeks after receiving the third vaccination, will be > - 5%.
and
To demonstrate that the SPR 4 weeks after completion of the three-dose regimen of Sci-B-Vac™ is superior to the SPR 4 weeks after completion of the three-dose regimen of Engerix-B® in older adults ≥ 45 years old i.e. the lower bound of the 95% two-sided CI of the difference between the SPR in the Sci-B-Vac™ arm minus the SPR in the Engerix-B® arm, achieved 4 weeks after receiving the third vaccination, will be > 5%. |
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E.2.2 | Secondary objectives of the trial |
To determine whether the SPR after receiving 2 vaccinations of Sci-B-Vac™, evaluated at 4 weeks and 20 weeks after receiving the second vaccination (just prior to receiving the third vaccination), is non-inferior to the SPR 4 weeks after receiving the third vaccination with Engerix-B®
To compare the safety and reactogenicity of Sci-B-Vac™ and Engerix-B®.
Please see protocol for Exploratory objectives |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
There are two sub studies a Clinical Laboratory sub study and a Cell mediated immunity direct against HBs described below.
Clinical Laboratory sub-study.
At select study sites, clinical laboratory parameters (hematology, biochemistry) will be assessed one week after each vaccination with either Sci-B-Vac or Engerix-B® and compared to baseline (pre-vaccination) values, as part of a clinical laboratory sub-study. All subjects enrolled at these select sites will be required to come for three additional visits and to provide four additional blood samples, beyond those required for the main study. The clinical laboratory sub-study will include at least 10% of all subjects enrolled to the entire trial.
Blood samples for the clinical laboratory sub-study will be collected at baseline (Day 0, Visit 1) prior to receiving any study vaccine, and at each of the three additional visits (additional visits A1, A2 and A3 in the Protocol: Appendix 2 Schedule of Events), to be scheduled 1 week after each vaccination with Sci-B-Vac™or EngerixB® on Study Day 7 (-3/+7 days), Study Day 35 (-3/+7 days) and Study Day 175 (-3/+7 days), respectively.
The following clinical laboratory parameters will be evaluated:
Hematology
o White blood cell count with differential
o Red blood cell count
o Hematocrit (HCT)
o Mean cell hemoglobin (MCH
o Mean cell hemoglobin concentration (MCHC)
o Mean corpuscular volume (MCV)
o Hemoglobin
o Platelet count
Biochemistry:
o Blood urea nitrogen (BUN), serum creatinine.
o Alkaline phosphatase (AP), alanine transaminase (ALT), aspartate transaminase (AST),
total and conjugated bilirubin, gamma-glutamyl-transferase (GGT)
Safety laboratory evaluations may be repeated if indicated (e.g. follow-up of a clinically significant
laboratory abnormality (from baseline assessment))
Optional sub study of cell-mediated immunity directed against HBs
Cell-mediated immunity directed against HBs and related mechanistic studies will also be studied on a small subset of subjects (~50-75 subjects/treatment arm), recruited from among the subjects participating in the clinical laboratory sub-study. Participation in the sub-study of cell-mediated immunity is optional, and will require a separate consent.
Subjects who agree to participate in the sub-study of cell-mediated immunity will be asked to provide 4 additional blood samples, beyond those required for the clinical laboratory sub-study, at V1 (Study Day 0) prior to vaccination and at each of three additional visits (A1, A2, A3) 1 week after each vaccination with either Sci-B-Vac™ or Engerix-B® (Study Days 7, 35, 175).
Lack of participation in the optional sub-study of cell-mediated immunity will not preclude participation the clinical laboratory sub-study or the main study |
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E.3 | Principal inclusion criteria |
Subjects must meet all the following criteria to be eligible:
1. Any gender.
2. Age ≥ 18 years.
3. In stable health as determined by a physical examination and laboratory tests values. Common chronic conditions such as, but not limited to, type 2 diabetes, high blood pressure, COPD, asthma will be accepted if the condition is well controlled, as determined by the investigator, and not meeting the exclusion criteria. For subjects > 65 years old, Frailty Index ≤3 17(see Appendix 1 of the protocol).
4. If female:
either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy),
OR
is of childbearing potential and must agree to use an adequate birth control method during the screening period and until the end of her participation in the study (effective birth control includes: 1) hormonal (implant, oral, vaginal, transdermal) contraceptives; 2) diaphragm with spermicide, condom (with or without spermicide); 3) intra-uterine devices; and 4) vasectomy of male partner; 5) abstinence from penile-vaginal intercourse (if the preferred and usual lifestyle of the subject)).
5. Able and willing to give consent.
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E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria will be excluded:
1.Previous vaccination with any HBV vaccine (licensed or experimental).
2.Treatment by immunosuppressant within 30 days of enrollment including but not limited to corticosteroids at a dose that is higher than an oral or injected physiological dose, or a prednisolone-equivalent dose >20 mg /day (Inhaled and topical steroids are allowed.
3.Known history of immunological function impairment, including but not limited to:
a) autoimmune diseases (e.g., multiple sclerosis, type 1 diabetes, myasthenia gravis, Crohn disease and other inflammatory bowel diseases, celiac disease, systemic lupus erythematosus, scleroderma, including diffuse systemic form and CREST syndrome, systemic sclerosis, dermatomyositis polymyositis, rheumatoid arthritis, juvenile idiopathic arthritis, autoimmune thyroiditis -including Hashimoto thyroiditis, Grave's or Basedow’s disease, immune thrombocytopenic purpura, autoimmune hemolytic anemia, autoimmune hepatitis, psoriasis, vitiligo, vasculitis, Guillain-Barré syndrome, Addison’s disease, Bell’s palsy and alopecia areata);
OR
b)secondary immunodeficiency disorders (e.g. resulting from HIV/AIDS (Acquired Immunodeficiency Syndrome caused by Human Immunodeficiency Virus infection), solid organ transplant, splenectomy);
OR
c) primary immunodeficiency disorders (e.g. common variable immune deficiency (CVID), Defective phagocytic cell function and neutropenia syndromes, complement deficiency).
4.Pregnancy or breastfeeding.
5.Immunization with attenuated vaccines (e.g. MMR) within 4 weeks prior to enrollment.
6.Immunization with inactivated vaccines (e.g. influenza) within 2 week prior to enrollment.
7.Has received blood products or immunoglobulin within 90 days of enrollment or likely to require blood products during the study period.
8.Subject in another clinical trial with an investigational drug or a biologic within 30 days of enrollment.
9.Has received granulocyte-macrophage colony stimulating factor (G/GM-CSF) or erythropoietin (EPO) within 30 days of enrollment or likely to require GM-CSF/erythropoietin during the study period.
10.Any history of cancer requiring chemotherapy or radiation within 5 years of randomization or current disease. Subject with a history of low risk basal cell carcinoma will be accepted (low risk being defined by the following: 1) location on the trunk of the body, arms, legs, cheeks, forehead, temples, scalp, neck or chin and 2) less than 2 cm, and 3) nodular or superficial, and 4) primary cancer that has not come back after treatment and 5) edge of the cancerous area is clear and smooth and 6) not located in or around nerves).
11.Any skin abnormality or tattoo that would limit post-vaccination injection site assessment.
12.History of allergic reactions or anaphylactic reaction to any vaccine component (Engerix-B® or Sci-B-Vac™).
13.Unwilling, or unable in the opinion of the investigator, to comply with study requirements, including the use of an adequate birth control method.
14.Immediate family members of study center staff (parents, sibling, children).
15.Current or past hepatitis B infection or prior vaccination as evidenced by HBV markers (anti-HBc, anti-HBs, HBsAg) at screening.
16.Known hepatitis C infection or positive Hepatitis C serology at screening, unless treated and cured (defined as documented sustained virologic response (SVR) or negative viral load ≥ 12 weeks after cessation of antiviral therapy).
17.Known human immunodeficiency virus (HIV) infection or positive HIV serology at screening.
18.Renal impairment with Glomerular Filtration Rate (GFR) ≤60 mL/min/1.73 m2 at screening.
19.Uncontrolled diabetes mellitus (defined as HbA1C >8.5%).
20.Uncontrolled hypertension (defined as an average SBP ≥150 mmHg or an average DBP ≥95 mmHg based on the last three measurements, in people diagnosed and treated for hypertension).
21.Any laboratory test abnormality that would be considered of Grade 1 severity or above as per Appendix 4 of the protocol and is considered as clinically significant by the investigator. Grade 3 severity or above is exclusionary, regardless of clinical assessment.
22.Diagnosis of advanced stage heart failure (New York Heart Association (NYHA) class III or IV – see Appendix 5 of the protocol) or Unstable Angina
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E.5 End points |
E.5.1 | Primary end point(s) |
Seroprotection rate 4 weeks after receiving third vaccination with either Sci-B-Vac™ or Engerix-B®, on Study Day 196. Seroprotection is defined as anti-HBs levels ≥ 10 mIU/mL in serum. Seroprotection rate is the percentage (%) of subjects achieving seroprotection. A validated quantitative antibody test will be used to measure anti-HBs levels in serum. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Study Day 196 (4 weeks post third vaccination ) |
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E.5.2 | Secondary end point(s) |
SPR on Study Days, 56 and 168, 4 weeks and 20 weeks after receiving the second Sci-BVac™ vaccination (just prior to receiving the third vaccination), and the SPR on Study Day 196, 4 weeks after receiving the third Engerix-B® vaccination.
Number (%) of subjects-reported, solicited (on the day of vaccination and during the next 6 days), unsolicited AE (on the day of vaccination and during the next 27 days), and number of Serious SAEs, medically significant events (condition prompting emergency room visit, physician visit not related to a common disease/not a routine visit or an SAE not related to a common disease) or new onset of chronic illness through Study Day 336.
Adverse events will be classified by Medical Dictionary for Regulatory Activities (MedDRA) system organ class and preferred term, severity, seriousness, investigator and Sponsor causality assessment, and time since vaccination.
Number (%) of subjects with abnormal vital signs, and/or physical examination findings compared to baseline.
Please see the protocol for the Exploratory End Points
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 |
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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) | 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 | Yes |
E.8.1.5 | Parallel group | No |
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 | 2 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 |
Belgium |
Canada |
Finland |
United States |
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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.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 8 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 8 |