| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Prophylaxis for Shigellosis induced by Shigella sonnei, Shigella flexneri 1b, Shigella flexneri 2a and Shigella flexneri 3a. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Prevention of diarrhoeal disease due to Shigella infection |
|
| 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 | 10040550 |
| E.1.2 | Term | Shigella infections |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 27.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10054178 |
| E.1.2 | Term | Shigella infection |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 | 10040542 |
| E.1.2 | Term | Shigella |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 | 10040547 |
| E.1.2 | Term | Shigella flexneri |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 | 10040551 |
| E.1.2 | Term | Shigella sonnei |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10004016 |
| E.1.2 | Term | Bacterial diarrhoea |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 | 10012735 |
| E.1.2 | Term | Diarrhoea |
| E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
| 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 evaluate the immunogenicity profile of the altSonflex1-2-3 vaccine (Dose A, Dose B and Dose C) administered at 9 and 15 months of age using anti-LPS/OAg ELISA.
• To evaluate the seroresponse of the altSonflex1-2-3 vaccine (Dose A, Dose B and Dose C) administered at 9 and 15 months of age using anti-LPS/OAg ELISA |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate the safety and reactogenicity of the altSonflex1-2-3 vaccine (Dose A, Dose B and Dose C) administered at 9 and 15 months of age.
• To evaluate the immunogenicity of co-administered MR-VAC administered at 9 and 15 months of age. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
All participants:
• Participants’ parent(s)/LAR(s), who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits).
• Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the participant prior to performance of any study specific procedure.
• Healthy participants as established by medical history, clinical examination, and laboratory assessment.
• Participants satisfying all screening requirements.
• Participants seronegative for hepatitis B, and hepatitis C.
• A male or female 9 months of age at the time of the first study intervention administration.
• Normal nutritional (weight-for-length) Z score (-2 standard deviations or greater).
• Previously completed routine childhood vaccinations to the best knowledge of the participant’s parent(s)/LAR(s).
• Born at a gestation period of ≥37 weeks to the best knowledge of the participant’s parent(s)/LAR(s).
• Participants negative for human immunodeficiency virus as confirmed by DNA polymerase chain reaction testing.
• Participants negative for HLA-B27 |
|
| E.4 | Principal exclusion criteria |
All participants:
• Known exposure to Shigella during lifetime of the participant as confirmed during interview with the participant’s parent(s)/LAR(s) or documented by participant’s records (e.g., history of microbiologically-confirmed Shigella infection).
• Progressive, unstable, or uncontrolled clinical conditions.
• History (known or suspected) of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention.
• Major congenital defects, as assessed by the investigator.
• Recurrent history or uncontrolled neurological disorders or seizures.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• Hypersensitivity (known or suspected), including allergy, to medicinal products, vaccines, or medical equipment whose use is foreseen in this study.
• Clinical conditions representing a contraindication to IM vaccination and blood draws.
• Any behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the participant’s ability to participate in the study.
• Acute disease and/or fever (defined as temperature ≥38.0°C) at the time of enrollment*.
*The participant can still be enrolled into the study at a time when the acute disease and/or fever has resolved.
• Any clinically significant* hematological and/or biochemical laboratory abnormality.
*The investigator should use his/her clinical judgment to decide which abnormalities are clinically significant.
• Confirmed positive COVID-19 test during the period starting 30 days before the first administration of study interventions (Day -30 to Day 1).
• Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.
• Acute or chronic clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by physical examination or laboratory
screening tests.
• Use of any investigational or non-registered product (drug, vaccine or invasive medical device)* other than the study intervention(s) during the period beginning 30 days before the first dose of study intervention(s) (Day - 30 to Day 1), or their planned use during the study period.
*Use of herbs and traditional treatments is not considered an exclusion criterion.
• Planned administration/administration of a vaccine/product in the period starting 21 days before the first dose and ending after the last dose of study intervention(s) administration* with the exception of COVID-19 vaccines and EPI vaccines (allowed by the protocol). The recommended time intervals for administration of these vaccines are at least 7 days before or 7 days after (at least 14 days before or 14 days after in case of live vaccines) each dose of study intervention administration.
• Administration of long-acting immune-modifying drugs at any time during the study period (e.g., infliximab).
• Prior receipt of an experimental Shigella vaccine or live Shigella challenge.
• Prior receipt of a TCV.
• Administration of immunoglobulins and/or any blood products or plasma derivatives, or bone marrow transplantation, from birth or planned administration during the study period.
• Chronic administration of immune-modifying drugs (defined as more than 14 days consecutive days in total) and/or planned use of long-acting immune-modifying treatments at any time up to the end of the study.
− Up to 3 months prior to the study intervention administration:
− For corticosteroids, this will mean prednisone equivalent≥0.5 mg/kg/day with maximum of 20 mg/day for pediatric participants. Inhaled and topical steroids are allowed.
− Up to 3 months prior to study intervention administration: long-acting immune-modifying drugs including among others immunotherapy (e.g., TNF-inhibitors), monoclonal antibodies, antitumoral medication.
*If emergency mass vaccination for an unforeseen public health threat (e.g., a pandemic) is recommended and/or organized by public health authorities outside the routine immunization program, the time period described above can be reduced provided it is used according to the local governmental recommendations and that sponsor is notified. When regulations allow, the recommended time intervals for administration of these vaccines are at least 7 days before or 7 days after (at least 14 days before or 14 days after in case of live vaccines) each dose of study intervention administration.
• Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention drug or invasive medical device.
• Any study personnel or immediate dependents, family, or household member.
• Child in care.
• Participants who do not meet eligibility criteria for administration of control vaccines. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Anti-serotype-specific Shigella LPS/OAg serum IgG GMCs/GMTs, as measured by ELISA, for each study intervention group.
2. Number of infants with at least a 4-fold increase in anti-serotypespecific Shigella LPS/OAg serum IgG, as measured by ELISA, for each study intervention group |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. before each study intervention administration (Day 1 and Day 169), and at Day 29 and Day 197
2. at Day 29 and Day 197 compared to baseline (Day 1), and at 28 days after dose 2(Day 197) compared to pre-administration dose 2 (Day 169) |
|
| E.5.2 | Secondary end point(s) |
1. Number of infants with solicited administration-site events during the 7 days period after each study intervention administration.
2. Number of infants with solicited systemic events during the 7 days period after each study intervention administration.
3. Number of infants with unsolicited AEs during the 28 days period after each study intervention administration.
4. Number of infants with SAEs during their entire study participation period.
5. Number of infants with deviations from laboratory reference values or baseline values of hematological, renal, and hepatic panel test results, at 7 days after each study intervention administration.
6. Anti-measles IgG concentrations, as measured by ELISA, before the first MR-VAC and at 28 days after the second MR-VAC vaccination.
7. Anti-rubella IgG concentrations, as measured by ELISA, before the first MR-VAC and at 28 days after the second MR-VAC vaccination.
8. Number of infants achieving anti-measles IgG concentrations of ≥150 mIU/mL and ≥200 mIU/mL, as measured by ELISA, at 28 days after the second MR-VAC vaccination.
9. Number of infants achieving anti-rubella IgG concentrations of ≥4 IU/mL and ≥10 IU/mL, as measured by ELISA, at 28 days after the second MR-VAC vaccination. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. at Day 1 and the 6 subsequent days after each study intervention administration on Day 1 and Day 169
2. at Day 1 and the 6 subsequent days after each study intervention administration on Day 1 and Day 169
3. at Day 1 and the 27 subsequent days after each study intervention administration on Day 1 and Day 169
4. from Day 1 to Day 197
5. at Day 8 and Day 176
6. at Day 1 and at Day 197
7. at Day 1 and at Day 197
8. at Day 197
9. at Day 197 |
|
| 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 | 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 safety of an alternative 2-dose vaccination schedule |
|
| 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 | 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 | 4 |
| E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
| E.8.4 | Will this trial be conducted at multiple sites globally? | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
| 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.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 1 |
Print
