E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Verification of immune response after booster immunisation with one dose of vaccine against tetanus and diphtheriae |
|
E.1.1.1 | Medical condition in easily understood language |
Verification of immune response after booster immunisation with one dose of vaccine against tetanus and diphtheriae |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
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 | 10054183 |
E.1.2 | Term | Tetanus immunization |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
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 | 10054129 |
E.1.2 | Term | Diphtheria immunisation |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
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 |
Primary objective of this trial is to demonstrate non-inferior immunogenicity (represented by seroconversion rate for tetanus and/or diphtheriae) of booster vaccination with the VACDITE vaccine compared to that of the reference vaccine (IMOVAX D.T. ADULT) in healthy adults.
|
|
E.2.2 | Secondary objectives of the trial |
Secondary objective of this trial is to demonstrate non-inferior immunogenicity (represented by modified seroconversion rates for tetanus and/or diphtheriae, GMC of antibodies against tetanus and/or diphtheriae and RA of tetanus and/or diphtheriae) of booster vaccination with the VACDITE vaccine compared to that of the reference vaccine (IMOVAX D.T. ADULT) in healthy adults.
Safety objective is to evaluate safety of the VACDITE vaccine on the base of reported adverse events during study follow-up, i.e. 28 days after booster immunisation. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject provides written informed consent with the study participation 2. Subjects must have written confirmation on previous immunisation against tetanus and diphtheriae not later than 15.9 years and not early than 9.9 years 3. Men and women aged 24.1- 64.9 years
|
|
E.4 | Principal exclusion criteria |
1. Subject with acute infectious diseases. 2. Subject allergic to any of the substances of the investigational medicinal product administered in clinical trial (i.e., test and reference vaccine). 3. Subject with Guillain-Barré syndrome or neuropathy, some anaphylactic or other allergic reactions after previous vaccination against tetanus and diphtheriae. 4. Pregnant woman and breastfeeding (anamnestically). 5. Subject with primary or secondary immunodeficiency (e.g. congenital immunodeficiency, HIV infection, organ or bone marrow transplantation, leukaemia, lymphoma, Hodgkin's disease, multiple myeloma, generalised malignancy, drugs or other causes induced immunodeficiency). 6. Subject with progressive or unstable neurological disorder. 7. Subject with severe thrombocytopenia or any coagulation disorder not allowing the intramuscular use. 8. Subject with blood product treatment, including immunoglobulins within the last 90 days prior to study entry. 9. Subject vaccinated less than 30 days inactivated or live vaccine prior to study entry. 10. Subject - pregnant or breast feeding women. Women of child bearing potential must have a negative urine or serum pregnancy test prior to enrolment.* 11. Subject unable to understand consent or follow study protocol. 12. Subject addicted to alcohol or drugs. 13. Subject currently participating in another clinical trial of a medication or in a trial that has taken place in the last 4 weeks. 14. A subject requiring tetanus vaccination after an injury
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary measured endpoint is the concentration of tetanus-specific antibodies and/or diphtheriae-specific antibodies before and after booster vaccination. They are used to calculate the seroconversion rate, i.e. the proportion of subjects who will have a minimum limit of measured antibodies after vaccination. Seroconversion rate will be considered in this study as the primary calculated endpoint. The primary endpoint in this trial is the seroconversion rate defined by 4-fold increase of antibody concentration, 4 weeks after booster immunisation, in relation to pre-vaccination antibody concentration. The minimum antibody concentration after immunisation must be 0.4 IU/ml, if pre-vaccination levels are lower than 0.1 IU/mL. The same definition of seroconversion rate is considered for both types of antibodies, i.e. against tetanus and/or diphtheriae. This seroconversion will be further reported as SCR4.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Before vaccine administration at the same day (V1) and 28 days after vaccine administration (V2). |
|
E.5.2 | Secondary end point(s) |
Whereas the selection of subjects is not performed exclusively from subjects who are seronegative (or naive) prior to the booster immunisation the seroconversion rate will be also assessed by modified definitions. The reason is that subjects with relatively high levels of pre-vaccination levels may respond with a lower increase of post-vaccination levels than those with a low pre-vaccination levels of antibodies. Therefore, there will be tested the seroconversion rate obtained from 2-fold increase of antibody concentration in subject with pre-vaccination levels ≥ 1.0 IU/mL. If the pre-vaccination levels are <1.0 IU/mL the seroconversion rate will be achieved under the condition of 4-fold increase with post-vaccination concentration of at least 0.4 IU/mL. This seroconversion rate will be further named as SCR2. A commercial kit used for serological assay has pre-determined measuring range. If the measured antibody concentrations above upper limit of such a range are considered to be less precise then 4-fold increase could be limited by a quarter of this upper limit, i.e. value ULR/4 IU/mL (upper limit of range divided by four). In this case, there will be tested the seroconversion rate obtained from 2-fold increase of antibody concentration in subject with pre-vaccination levels ≥ ULR/4 IU/mL. If pre-vaccination levels are <URL/4 IU/mL the seroconversion rate will be achieved under the condition of 4-fold increase with post-vaccination concentration of at least 0.4 IU/mL. This seroconversion rate will be further named as SCR-URL/4. As an indicator of long-term protection, the proportion of subjects with a post-vaccination antibody level of 1.0 IU/mL or greater will be evaluated as a secondary end-point, i.e. seroconversion rate SCR1. All modified seroconversion rates will be used for both types of antibody against tetanus and diphtheriae. Because both vaccines should not differ in immunogenicity the composite seroconversion rate will be applied. The composite rates will be achieved if both post-vaccination tetanus and/or diphtheriae antibody concentrations satisfy the definitions of seroconversion rate reported above, i.e. SC4, SC2, SC-ULR/4 or SC1.The composite rates (CR4, CR2, CR-ULR/4 and CR1) will be evaluated as secondary endpoint. The immune response to vaccination is characterised not only by the rate of seroconversion but also by the post-vaccination levels of antibodies. Therefore, geometric mean concentrations of antibodies against tetanus and/or diphtheriae will be used as secondary endpoint. Similarly, as seroconversion rates can be affected by the pre-vaccination levels the postvaccination concentrations can be also influenced. Therefore, the rise in antibodies (RA), that reflects pre- and post-vaccination levels, will be assessed as the further secondary endpoint.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Before vaccine administration at the same day (V1) and 28 days after vaccine administration (V2). |
|
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 | No |
E.6.5 | Efficacy | Yes |
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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
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 | 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 | 4 |
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 | 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
|
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |