E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention against Clostridium difficile infection |
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E.1.1.1 | Medical condition in easily understood language |
Clostridium difficile is a common bacterium that lives in the human gut. It can also cause diarrhea and can lead to severe intestinal disease. A vaccine is developed to prevent against infection. |
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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 | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10054236 |
E.1.2 | Term | Clostridium difficile infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 confirm the optimal dose and formulation of VLA84 in healthy adults (aged ≥50 years) |
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E.2.2 | Secondary objectives of the trial |
To investigate the immunogenicity of VLA84 in healthy adults (aged ≥50 years) up to 6 months after the last vaccination
To characterize the safety of VLA84 in healthy adults (aged ≥50 years) up to 6 months after the last vaccination
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects aged ≥50 years of good general health, including subjects with pharmacologically controlled conditions like hypercholesterolemia, hypertension, or type 2 diabetes mellitus. 2. Informed consent form has been signed and dated
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E.4 | Principal exclusion criteria |
1. Subjects with any confirmed or suspected prior Clostridium difficile infection episode 2. Previous vaccination against Clostridium difficile with any (investigational) vaccine or receipt of (investigational) monoclonal antibodies against Clostridium difficile toxins 3. Use of any other investigational or non-registered medicinal product within 30 days prior to VLA84 vaccination at Visit 1 (Day 0) and throughout the entire study period. 4. Active or passive vaccination four weeks before first vaccination at Visit 1 and during the entire study period, except for influenza (seasonal or pandemic) and pneumococcal vaccines which may be administered outside a 7-days interval before and after any trial vaccination 5. Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year or surgically sterile) 6. Known thrombocytopenia, bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion or until Visit 4 (Day28), contraindicating IM vaccination as judged by the investigator 7. Clinically relevant renal, hepatic, cardiac, pulmonary or central nervous disorders, as judged by the investigator. Subjects with hypercholesterolemia, hypertension, or type 2 diabetes mellitus requiring medication are allowed if disease is adequately controlled 8. Receipt of blood or blood-derived products in the past 3 months or anticipation of such products during the study period 9. Known congenital, hereditary or acquired immunodeficiency, including known infection with human immunodeficiency virus (HIV), administration of chronic (defined as longer than 14 days) immunosuppressants or other immune-modifying drugs within 30 days prior to VLA84 vaccination at Visit 1 (Day 0) and during the study until Visit 5 (Day 35). For corticosteroids this means prednisone or equivalent ≥ 0.05 mg/kg/day; topical and inhaled steroids are allowed. Periodic steroid injections, e.g., intra-articular, are are not allowed within 30 days prior to first VLA84 vaccination at Visit 1 (Day 0) and until Visit 5 (Day 35) 10. History of autoimmune disease, including Type I Diabetes mellitus. Subjects with vitiligo or thyroid disease taking thyroid hormone replacement are not excluded 11. Any malignancy in the past 5 years. If treatment for cancer was successfully completed more than 5 years ago and the malignancy is considered to be cured, the subject may be enrolled 12. Known hypersensitivity or allergic reactions to one of the components of the vaccine 13. Inability or unwillingness to provide informed consent 14. Persons who are committed to an institution (by virtue of an order issued either by the judicial or the administrative authorities) 15.Persons who are in a dependent relationship with the sponsor, an investigator or other study team members (i.e., children, partner/spouse, siblings, parents) as well as employees of the investigator or study center personnel |
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E.5 End points |
E.5.1 | Primary end point(s) |
Seroconversion Rate (SCR, defined as proportion of subjects achieving a ≥4-fold increase in antibody titer from Day 0) for IgG against both Toxin A and Toxin B on Day 56 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Immunogenicity Endpoints: + SCR for IgG against both Toxin A and Toxin B on Days 0, 14, 28, 35, 120 and 210 + SCR for IgG against Toxin A on Days 0, 14, 28, 35, 56, 120 and 210 + SCR for IgG against Toxin B on Days 0, 14, 28, 35, 56, 120 and 210 + Geometric Mean Titer (GMT) for IgG against Toxin A as determined by ELISA on Days 0, 14, 28, 35, 56, 120 and 210 + Geometric Mean Titer (GMT) for IgG against Toxin B as determined by ELISA on Days 0, 14, 28, 35, 56, 120 and 210 + Responder Rate (defined as proportion of subjects achieving a ≥4-fold increase in neutralizing antibody titer from Day 0) for neutralizing antibodies against both Toxin A and Toxin B on Days 0, 35, 56, 120* and 210 + Responder Rate for Toxin A neutralizing antibodies on Days 0, 35, 56, 120* and 210 + Responder Rate for Toxin B neutralizing antibodies on Days 0, 35, 56, 120* and 210 + GMT for Toxin A neutralizing antibodies as determined by Toxin Neutralization Assay on Days 0, 35, 56, 120* and 210 + GMT for Toxin B neutralizing antibodies as determined by Toxin Neutralization Assay on Days 0, 35, 56, 120* and 210 + SCR for IgG against Toxin A, against Toxin B and against both Toxin A and Toxin B on Days 0, 14, 28, 35, 56, 120 and 210, stratified by age group (subjects 50 - < 65 years and 65 years and older) + GMT for IgG against Toxin A and against Toxin B on Days 0, 14, 28, 35, 56, 120 and 210, stratified by age group (subjects 50 - < 65 years and 65 years and older) + Responder Rate for neutralizing antibodies against Toxin A, against Toxin B and against both Toxin A and Toxin B on Days 0, 35, 56, 120* and 210, stratified by age group (subjects 50 - < 65 years and 65 years and older) + GMTs for Toxin A neutralizing antibodies and for Toxin B neutralizing antibodies as determined by Toxin Neutralization Assay on Days 0, 35, 56, 120* and 210, stratified by age group (subjects 50 - < 65 years and 65 years and older)
Safety Endpoints: + Rate of SAEs to Day 56 and Day 210 + Rate of related SAEs to Day 56 and Day 210 + Rate of unsolicited AEs to Day 56 and Day 210 (incl. clinically significant laboratory parameter changes) + Rates of related unsolicited AEs to Day 56 and Day 210 (incl. clinically significant laboratory parameter changes) + Rates of solicited local and systemic AEs within 7 days after each and after any vaccination + Rates of SAEs, related SAEs, unsolicited AEs (incl. clinically significant laboratory parameter changes) and related unsolicited AEs, to Day 56 and Day 210, stratified by age group (subjects 50 - < 65 years and 65 years and older) + Rates of solicited local and systemic AEs within 7 days after each and after any vaccination, stratified by age group (subjects 50 - < 65 years and 65 years and older) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
on Days 0, 14, 28, 35, 56, 120 and 210 (detailed at each endpoint in E.5.2) |
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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 | 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 |
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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) | 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 | 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 |
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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 | 4 |
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 | 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 |
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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 | |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |