| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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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 | HLT |
| E.1.2 | Classification code | 10036017 |
| E.1.2 | Term | Poliomyelitis viral infections |
| E.1.2 | System Organ Class | 100000004862 |
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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 |
The primary objectives of the study are
- To assess the safety (serious adverse events [SAEs] and severe adverse events [AEs]) of novel monovalent live attenuated oral serotype 2 poliovirus vaccine (nOPV2) candidate 1 and novel monovalent live attenuated oral serotype 2 poliovirus vaccine (nOPV2) candidate 2 in healthy OPV-vaccinated adults, relative to historical controls given Sabin OPV2;
- To compare the immunogenicity (seroprotection rate) of novel monovalent live attenuated oral serotype 2 poliovirus vaccine (nOPV2) candidate 1 and novel monovalent live attenuated oral serotype 2 poliovirus vaccine (nOPV2) candidate 2 in healthy OPV-vaccinated adults to historical controls given Sabin OPV2;
- To assess the safety (serious adverse events [SAEs] and severe adverse events [AEs]) of nOPV2 candidate 1 and nOPV2 candidate 2 in healthy IPV-only vaccinated adults, compared with placebo.
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| E.2.2 | Secondary objectives of the trial |
Secondary objectives are
- To assess the safety (any solicited and unsolicited AEs, laboratory assessments) of nOPV2 candidate 1 and nOPV2 candidate 2 in healthy OPV-vaccinated adults, compared with historical controls given Sabin OPV2;
- To assess the safety (any solicited and unsolicited AEs, laboratory assessments) of nOPV2 candidate 1 and nOPV2 candidate 2 in healthy IPV-only vaccinated adults, compared with placebo;
- To compare the immunogenicity (seroconversion rate, median antibody titer (post-vaccination)) of nOPV2 candidate 1 and nOPV2 candidate 2 in healthy OPV-vaccinated adults, with historical control of Sabin OPV2;
- To assess the immunogenicity (seroprotection rate, seroconversion rate, median post-vaccination antibody titer) of nOPV2 candidate 1 and nOPV2 candidate 2 in healthy IPV-only vaccinated adults. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. For Groups 1, 2, 3 and 4: healthy males or females, from 18 to 50 years of age inclusive, having previously received at least 3 doses of OPV more than 12 months before the start of the study;
2. For Groups 5, 6 and 7: healthy males or females, from 18 to 50 years of age inclusive, having previously received at least 3 doses of IPV more than 12 months before the start of the study;
3. Having residence in Belgium;
4. In good physical and mental health as determined on the basis of medical history and general physical examination performed at Day 0;
5. Female subjects of childbearing potential must agree to the use of an effective method of birth control throughout the study and up to 3 months after last vaccine dose (see Section 7);
6. Willing to adhere to the prohibitions and restrictions specified in this protocol (see Section 7);
7. Informed Consent Form (ICF) and Code of Conduct signed voluntarily by the subject before any study-related procedure is performed, indicating that the subject understands the purpose of any procedures required for the study and is willing to participate in the study.
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| E.4 | Principal exclusion criteria |
1. A condition that, in the opinion of the Investigator, could compromise the well being of the subject or course of the study, or prevent the subject from meeting or performing any study requirements;
2. For Groups 5, 6 and 7: ever having received any OPV in the past;
3. Any travel to polio endemic countries or countries with evidence of recent (within last 6 months) wild or vaccine-derived poliovirus circulation during the total duration of the study
4. Professional handling of food, catering or food production activities during the total duration of the study;
5. Having Crohn’s disease or ulcerative colitis or having had major surgery of the gastrointestinal tract involving significant loss or resection of the bowel;
6. A known allergy, hypersensitivity, or intolerance to the study vaccine or the placebo, or to any of their components or to any antibiotics;
7. Any confirmed or suspected immunosuppressive or immunodeficiency condition (including human immunodeficiency virus [HIV] infection, hepatitis B or C infections or total serum IgA level below lab lower limit of normal (LNN));
8. Will have household or professional contact with known immunosuppressed people or people without full polio vaccination (i.e. complete primary infant immunization series), e.g. babysitting during the total duration of the study;
9. Neonatal nurses or others having professional contact with children under 6 months old during the total duration of the study;
10. Chronic administration (i.e., longer than 14 days) of immunosuppressant drugs or other immune-modifying drugs within 6 months prior to the first vaccine dose or planned use during the study. For instance, for corticosteroids, this means prednisone, or equivalent, ≥ 0.5 mg/kg/day (inhaled and topical steroids are allowed whereas intra-articular and epidural injection/administration of steroids are not allowed);
11. Presence of contraindications to administration of the study vaccine on Day 0: acute severe febrile illness deemed by the Investigator to be a contraindication for vaccination or persistent diarrhea or vomiting;
12. Indications of drug abuse or excessive use of alcohol at Day 0 (males: > 21 units per week (m); females > 14 units per week);
13. Being pregnant or breastfeeding. Women of childbearing potential will undergo a urine pregnancy test at each vaccination visit. Subjects with a positive pregnancy test will be excluded;
14. Participation in another clinical study within 28 days prior to entry in this study or receipt of any investigational product (drug or vaccine) other than the study vaccine within 28 days prior to the first administration of study vaccine, or planned use during the study period;
15. Administration of any vaccine other than the study vaccine within 28 days prior to the first dose of study vaccine and during the entire study period;
16. Administration of any polio vaccine within 12 months before the start of the study;
17. Having had a transfusion of any blood product or application of immunoglobulins within the 4 weeks prior to the first administration of study vaccine or during the study;
18. Subject is an employee of the Investigator or study site, with direct involvement in the proposed study or other studies under the direction of that Investigator or study site, or is a family member of an employee or the Investigator, or was a study subject in the historical control studies UAM1 or UAT1 or in the study UAM4a;
19. Having a family or household member participating in the study CVIA 065 or being a study subject in the study CVIA 065.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Safety: The following endpoints will be evaluated by group and overall:
- incidence, type and causality of SAEs and severe§ AEs throughout the study period.
Immunogenicity:
- seroprotection rate of type 2 polio antibodies at Day 28, following a single dose of nOPV2 candidate 1 (combined Groups 1 and 2) compared with the seroprotection rate of type 2 polio antibodies at Day 28 in the historical control mOPV2 study (combined group 1 and 2) (see annex).
- seroprotection rate of type 2 polio antibodies at Day 28, following a single dose of nOPV2 candidate 2 (combined Groups 3 and 4) compared with the seroprotection rate of type 2 polio antibodies at Day 28 in the historical control mOPV2 study (combined Groups 1 and 2) (see annex).
Seroprotection is defined as type 2-specific antibody titers ≥ 1:8.
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
safety throughout the study
immunogenicity: at Day 28 |
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| E.5.2 | Secondary end point(s) |
Safety: The following endpoints will be evaluated by group and overall:
- incidence, type, causality and severity of solicited adverse events for days 0-7 in Groups 1 and 2 combined and days 28-35 in Group 2;
- incidence, type, causality and severity of solicited adverse events for days 0-7 in Groups 3 and 4 combined and days 28-35 in Group 4;
- incidence, type, causality and severity of solicited adverse events for days 0-7 and days 28-35 in Groups 5, 6 and 7;
- incidence, type, causality and severity of unsolicited adverse events throughout the study period in all groups;
- incidence, causality and description of deviations from normal safety labs at Day 0, Day 7, Day 14 and Day 28 for Groups 1 through 4, and at Day 35, Day 42 and Day 56 for Groups 2 and 4;
- incidence, causality and description of deviations from normal safety labs at Day 0, Day 7, Day 14, Day 28, Day 35, Day 42 and Day 56 for Groups 5, 6, and 7.
Immunogenicity:
- Median titers of type 2 polio antibodies at Day 28 in Groups 1 and 2 combined;
- Median titers of type 2 polio antibodies at Day 28 in Groups 3 and 4 combined;
- Median titers of type 2 polio antibodies at Day 28 in Groups 5, 6 and 7.
- Seroprotection rate and median titers of type 2 polio antibodies at Day 56 in Groups 2 and 4;
- Seroprotection rate of type 2 polio antibodies at Day 28 and at Day 56 in Groups 5, 6 and 7.
- Seroconversion rate of type 2 polio antibodies at Day 28 for Groups 1 and 2 combined and at Day 56 in Group 2;
- Seroconversion rate of type 2 polio antibodies at Day 28 for Groups 3 and 4 combined and at Day 56 in Group 4;
- Seroconversion rate of type 2 polio antibodies at Day 28 and at Day 56 for Groups 5, 6 and 7.
Seroconversion is defined as a change from seronegative to seropositive and antibody titers of ≥1:8, and in seropositive subjects, as an antibody titer increase of ≥ 4-fold over baseline titers.
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
safety:
1) days 0-7 in Groups 1 and 2 combined and days 28-35 in Group 2
2) days 0-7 in Groups 3 and 4 combined and days 28-35 in Group 4
3)days 0-7 and days 28-35 in Groups 5,6 and 7
4) throughout the study
5)Day 0, Day7, Day 14, D28 for Groups 1 through 4 and D35,D42,D56 for Groups 2 and 4
Immunogenicity:
1) Day 28 in Groups 1 and 2 combined
2) Day 28 in Groups 3 and 4 combined
3) Day 28 in Groups 5,6, 7 |
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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 |
| Immunogenicity and viral shedding |
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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 | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| partial blind: single blind for OPV- subjects and double blind for IPV-vaccinated subjects |
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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 | 7 |
| 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 | 2 |
| 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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completion of all study related procedures 42 d after last study vaccination and PCR-neg shedding on 3 consecutive stool samples (max 1/d). If type 2 virus shedding is detected by PCR on 1 of last 3 scheduled samples the study duration for this individual will be extended. As soon as these results are known ( +/-3 w after last sample),subject will further collect 3 consecutive samples after the last per protocol sample and repeat this until shedding is PCR -neg on 3 consecutive samples.
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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 | 10 |
| E.8.9.1 | In the Member State concerned days | |
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