| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Active booster immunization against tetanus, diphtheria and pertussis |
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| E.1.1.1 | Medical condition in easily understood language |
| The vaccine is given to healthy individuals to prevent the tetanus, diphtheria and whooping cough diseases |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10021431 |
| E.1.2 | Term | Immunisations |
| 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 |
Phase II: To assess the reactogenicity and safety of a single dose of SIIPL Tdap in comparison with a single dose of Boostrix® in healthy participants of age 18 to 65 years.
Phase III: To demonstrate non-inferiority of SIIPL Tdap with a margin of 10% compared to Boostrix® in terms of seroprotection rates against diphtheria and tetanus 30 days after vaccination, in healthy participants of age 4 to 65 years. To demonstrate non-inferiority of SIIPL Tdap with a margin of 10% compared to Boostrix® in terms of booster response to pertussis toxoid (PT), filamentous hemagglutinin (FHA) and pertactin (PRN), 30 days after vaccination, in healthy participants of age 4 to 65 years.
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| E.2.2 | Secondary objectives of the trial |
Phase II:
•To demonstrate seroprotection against diphtheria and tetanus.
•To assess booster response rates to SIIPL Tdap and Boostrix® vaccines
•To assess immune responses of SIIPL Tdap as compared to Boostrix®
• To assess percentage of seropositive participants against pertussis antigens
Phase III:
• To assess booster response rates to SIIPL Tdap and Boostrix® vaccines
• To assess immune responses of SIIPL Tdap as compared to Boostrix®
• To determine percentage of seropositive participants against pertussis antigens
• To assess the reactogenicity and safety of single dose of SIIPL Tdap vaccine in comparison with Boostrix® vaccine
For a complete description be referred to the study protocol. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Participants aged 18 years and above who had provided written informed consent. Participants between 7 and 17 years had given their written informed assent in addition to both parents'/legal guardians written informed consents. For participants below 7 years, the written informed consent of both parents/legal guardians is sufficient without the participant's assent. Participants reaching the age of 18 years during the participation in the clinical study have to provide a written informed consent in addition to the already provided written consent as adolescent.
2. Healthy male or female participants aged 4 years to 65 years on the day of enrollment.
Phase II part of the study will enroll adults age 18 to 65 years.
Phase III part of the study will enroll adults age 18 to 65 years, adolescents age 12 to 17 years, and children age 4 to 11 years.
3. Healthy participants as established by medical history, physical examination during screening and as per the clinical judgment of the Investigator.
4. Participants'/parents'/legal guardians' willingness and ability to comply with the requirements of the protocol.
5. In the phase II part of the study, WOCBP who either abstain from sexual intercourse, have a sterile partner or practice a highly effective method of contraception. Female participant who has practiced highly effective method of contraception for 30 days prior to vaccination and agrees to continue the highly effective method of contraception for 30 days after vaccination.
6. Based on the Summary of Product Characteristics (1), Boostrix® may be administered to adolescents and adults with unknown vaccination status or incomplete vaccination against diphtheria, tetanus and pertussis as part of an immunization series against diphtheria, tetanus and pertussis. Hence, Boostrix® and thus SIIPL Tdap may be administered to adolescents and adults with unknown vaccination status or incomplete vaccination in this study. |
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| E.4 | Principal exclusion criteria |
1. Children (Cohort 3): History of previous vaccination against diphtheria, tetanus and pertussis with either the study vaccine or another vaccine in the past 4 years. The date of last injection with diphtheria, tetanus and pertussis (DTP) vaccine should be collected.
2. Adolescents (Cohort 2) and adults (Cohort 1): History of previous vaccination against diphtheria, tetanus and pertussis with either the study vaccine or another vaccine (except tetanus- or Td-prone wound management for adults and/or for tetanus or Td vaccination in pregnant women) in the past 5 years. The date of last injection with DTP vaccine should be collected.
3. History of tetanus, diphtheria or pertussis infection (confirmed either clinically, serologically or microbiologically).
4. History of administration of any investigational or non-registered drug, or any vaccine other than the study vaccines within 30 days prior to administration of study vaccines or planned during the course of study participation.
5. History of a severe allergic reaction (e.g. anaphylaxis) after a previous dose of any DT-, TT- or pertussis antigen-containing vaccine or to any component (active substances or excipients) of the study vaccines.
6. Participants who experienced an Arthus-type hypersensitivity reaction following a prior dose of a tetanus toxoid-containing vaccine unless at least 10 years have elapsed since the last dose of tetanus toxoid-containing vaccine. An Arthus-type hypersensitivity reaction is a type of local type III hypersensitivity reaction, characterized by formation of immune complexes and deposition of these antigen/antibody complexes mainly in the vascular walls, serosa (pleura, pericardium, synovium), and glomeruli.
7. History of following events that are known to have occurred in temporal relation to receipt of pertussis-containing vaccine: temperature ≥40°C within 48 hours of vaccination, not due to another identifiable cause; collapse or shock-like state (hypotonic-hyporesponsiveness episode) within 48 hours of vaccination; persistent, inconsolable crying lasting ≥ 3 hours, occurring within 48 hours of vaccination; convulsions with or without fever, occurring within 3 days of vaccination.
8. History of Guillain-Barré syndrome or brachial neuritis that occurred within 6 weeks of receipt of a prior vaccine containing TT.
9. History of encephalopathy (e.g. coma, decreased level of consciousness, prolonged seizures) within 7 days of administration of a previous dose of a pertussis antigen-containing vaccine that is not attributable to another identifiable cause.
10. History of transient thrombocytopenia or a bleeding disorder following an intramuscular administration.
11. History of neurological complications following an earlier vaccination against diphtheria and/or tetanus.
12. History of any major pulmonary, cardiovascular, renal, neurological, metabolic, gastrointestinal, hepato-biliary, hematological functional abnormality, or mental disability.
13. History of progressive or unstable neurologic conditions (e.g. cerebrovascular events).
14. Acute illness (moderate or severe) and/or fever (axillary temperature ≥38°C) at the time of vaccination or during the 72 hours prior to the vaccination. Vaccination of participants with fever (axillary temperature ≥ 38°C) at the time of vaccination or during the 72 hours prior to the vaccination should be delayed to a time point when the participant is fully recovered and fever-free. Vaccines can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection without fever.
15. History of receipt of a blood transfusion, other blood products, or immunoglobulins in 3 months prior to study vaccination, or planned administration during the active study period.
16. Participants with altered immunocompetence such as participants with ongoing cancer treatment, human immunodeficiency virus (HIV) infection, organ transplant or any other active immune system disorder. The Investigator needs to judge if the participant can participate in a vaccine study.
17. Chronic administration (defined as more than 14 days in total) of immunosuppressant or other immune modifying drugs during the period starting 6 months prior to the study vaccine dose or planned administration during the active study period (up to Visit 3 [Day 30 (+7 days)]). (For corticosteroids, this will mean prednisone ≥0.5 mg/kg/day or equivalent. However, inhaled or topical steroids are allowed.)
18. Females who are pregnant or breastfeeding.
19. Participant has any plans to permanently relocate from the area prior to the completion of the study or to leave for an extended period of time when study visits would need to be scheduled.
20. Concurrent participation in another clinical study investigating a vaccine, drug, medical device, or medical procedure in the 30 days preceding the study vaccination or during the course of the study. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Phase II:
• Adverse events (AEs)
a) The incidence rate, severity and relationship to investigational medicinal product (IMP) of AEs and serious AEs (SAEs) during initial 30 minutes after SIIPL Tdap or Boostrix® vaccination.
b) The incidence rate, severity and relationship to IMP of AEs and SAEs during 7-day follow-up period after SIIPL Tdap or Boostrix® vaccination.
c) The incidence rate, severity and relationship to IMP of AEs and SAEs during 30-day follow-up period, post-vaccination with SIIPL Tdap and Boostrix®.
Phase III:
• Diphtheria toxoid (DT) and Tetanus toxoid (TT) immunogenicity
a) Seroprotection status against DT* 30 days after vaccination with SIIPL Tdap or Boostrix®.
*A seroprotected participant is defined as a participant with anti-DT antibody concentrations above or equal (≥) to 0.1 IU/ml (international units per milliliter).
b) Seroprotection status against TT** 30 days after vaccination with SIIPL Tdap or Boostrix®.
**A seroprotected participant is defined as a participant with anti-TT antibody concentrations above or equal (≥) to 0.1 IU/ml.
• Booster response to pertussis antigens
a) Booster response*to PT 30 days after vaccination with SIIPL Tdap or Boostrix®.
b) Booster response* to FHA 30 days after vaccination with SIIPL Tdap or Boostrix®.
c) Booster response* to PRN 30 days after vaccination with SIIPL Tdap or Boostrix®.
*Booster responses to pertussis (PT, FHA and PRN) antigens are defined as:
In initially seronegative participants < lower limit of quantification (LLOQ) post vaccination antibody concentrations ≥4x LLOQ.
In initially seropositive participants with pre-vaccination antibody concentrations ≥ LLOQ and <4x LLOQ, an increase of at least 4 times the pre-vaccination antibody concentration. In initially seropositive participants with antibody concentrations ≥4x LLOQ, an increase of at least 2 times the pre-vaccination antibody concentration. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Throughout the conduct of the study |
|
| E.5.2 | Secondary end point(s) |
Phase II:
• DT and TT immunogenicity
a) Seroprotection status against DT*, 30 days after vaccination with SIIPL Tdap or Boostrix®.
b) *A seroprotected participant is defined as a participant with anti-DT antibody concentrations above or equal (≥) to 0.1 IU/ml.
c) Seroprotection status against TT**, 30 days after vaccination with SIIPL Tdap or Boostrix®.
d) **A seroprotected participant is defined as a participant with anti-TT antibody concentrations above or equal (≥) to 0.1 IU/ml.
• Booster response for DT*, TT*, PT**, FHA** and PRN** 30 days after vaccination with SIIPL Tdap or Boostrix®.
*Booster responses to DT and TT are defined as (1):
In initially seronegative participants, i.e., pre vaccination antibody titers <0.1 IU/ml, post vaccination antibody concentrations ≥0.4 IU/ml.
In initially seropositive participants, i.e., pre vaccination antibody titers ≥0.1 IU/ml, an increase of at least 2 times the pre-vaccination concentration.
*Booster responses to pertussis (PT, FHA and PRN) antigens are defined as:
In initially seronegative participants < LLOQ post vaccination antibody concentrations ≥4x LLOQ.
In initially seropositive participants with pre-vaccination antibody concentrations ≥ LLOQ and <4x LLOQ, an increase of at least 4 times the pre-vaccination antibody concentration.
In initially seropositive participants with antibody concentrations ≥4x LLOQ, an increase of at least 2 times the pre-vaccination antibody concentration.
• GMCs for anti-DT, anti-TT, anti-PT, anti-FHA, and anti-PRN, 30 days after vaccination with SIIPL Tdap or Boostrix®.
• Seropositive participants against pertussis antigens (PT, FHA and PRN), i.e., with antibody titers ≥ LLOQ against each antigen, 30 days after vaccination with SIIPL Tdap or Boostrix®.
Phase III:
• Booster responses* to SIIPL Tdap and Boostrix® vaccines, with respect to anti-DT and anti-TT, 30 days after the vaccination.
*Booster responses to DT and TT are defined as (1):
In initially seronegative participants, i.e., pre vaccination antibody titers <0.1 IU/ml, post-vaccination antibody concentrations ≥0.4 IU/ml.
In initially seropositive participants, i.e., pre-vaccination antibody titers ≥0.1 IU/ml, an increase of at least 2 times the pre-vaccination concentration.
• GMCs for anti-DT, anti-TT, anti-PT, anti-FHA, and anti-PRN, 30 days after vaccination.
• Seropositive participants against pertussis antigens (PT, FHA and PRN), i.e., with antibody titers ≥ LLOQ against each antigen, 30 days after vaccination with SIIPL Tdap or Boostrix®.
• The incidence rate, severity and relationship to IMP of AEs and SAEs during initial 30 minutes, 7 days follow-up period and 30 days follow-up period after SIIPL Tdap or Boostrix® vaccination. |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Throughout the conduct of the study |
|
| 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 | Yes |
| 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 |
| Immunization (booster immunization) |
|
| 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) | 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 | 20 |
| 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
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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 | 0 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
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