| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| PR5I is developed to provide active immunization against diphtheria, tetanus, pertussis, poliomyelitis (caused by poliovirus Types 1, 2 and 3), invasive disease caused by Haemophilus influenza type b and infection caused by all known subtypes of hepatitis B virus. |
| PR5I è sviluppato per fornire immunizzazione attiva contro la difterite, tetano, pertosse, poliomelite (causate da poliovirus Tipi 1, 2 e 3), patologie invasive causate da Haemofilus influenza tipo B ed infezione causata da tutti i sotto tipi del virus dell'epatite B. |
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| E.1.1.1 | Medical condition in easily understood language |
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| 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 | 14.1 |
| 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 | 14.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10019743 |
| E.1.2 | Term | Hepatitis B virus (HBV) |
| E.1.2 | System Organ Class | 10022891 - Investigations |
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| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10054181 |
| E.1.2 | Term | Hepatitis B 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 | 14.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10039242 |
| E.1.2 | Term | Routine childhood immunisation |
| E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 evaluate the immunogenicity of PR5I when given at 2, 4, and 11 to 12 months of age. |
| Valutare l'immunogenicità di PR5I quando somministrato ai mesi 2, 4, e da 11 a 12 mesi di età. |
|
| E.2.2 | Secondary objectives of the trial |
| 1)to compare the post-infant series anti-PRP response elicited by PR5I to that of INFANRIX™ hexa. 2)To compare the immunogenicity resp. elicited by PR5I to that of INFANRIX™ hexa when given at 2,4,11 to 12 mm. 3)To evaluate the immunog. of Rotarix™ when administered concomitantly with PR5I4)To describe the safety profile associated with the administr.of each dose of PR5I or INFANRIX™ hexa when given concomitantly with Prevenar 13™ and Rotarix™.5)To describe fever occurring within 5 days after the administration of each dose and after all doses of PR5I or INFANRIX™ hexa when given concomitantly with Prevenar 13™ and Rotarix™ or RotaTeq™.6)To describe the %of subjects with solicited injection-site AEs and solicited systemic AEs within 5 dd after each dose and after all doses of PR5I or INFANRIX™ hexa when coadmin.with other recommended vaccines7)To summarize the incidence of SAEs |
| Il disegno dello studio ha lo scopo di (1) valutare l'accettabilità e non inferiorità di PR5I rispetto al prodotto di controllo approvato, (2) valutare l'immunogenicità di Rotarix™ (vaccino antirotavirus, orale, vivo) somministrato in concomitanza e (3) descrivere i profili di sicurezza e tollerabilità di PR5I quando somministrato con vaccini pediatrici approvati di uso comune, con una posologia che prevede 2 dosi in età neonatale e 1 dose di richiamo (2+1). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| To be randomized and receive the first study vaccinations, subjects must meet all inclusion criteria. 1. Subject is a healthy infant and is greater than or equal to 46 days and less than or equal to 89 days of age on the day of vaccination. 2. Subject's parent(s)/legal representative understand the study procedures, alternate treatments available, and risks involved with the study, and voluntarily agree to participate by giving written informed consent. 3. Subject's parent(s)/legal representative are able to read, understand, and complete study questionnaires (i.e., the Vaccination Report Card [VRC]). 4. Subject is able to attend all scheduled visits and to comply with the study procedures. 5. Subject's parent(s)/legal representative have access to a telephone. |
| 1. Neonati sani da 46 a 89 giorni di vita al momento della vaccinazione 2. i genitori/legali rappresentanti del neonato devono aver compreso le procedure in studio, i trattamenti alternativi, i rischi e volontariamente acconsentire la partecipazione con consenso firmato 3.i genitori/legali rappresentanti del neonato devono leggere, capire, e completare questionari di studio4. i soggetti devono partecipare alle visite richieste ed essere complianti con le procedure dello studio 5.i genitori/legali rappresentanti del neonato devono avere a disposizione un telefono |
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| E.4 | Principal exclusion criteria |
| To be randomized and receive the first study vaccinations, subjects must not meet any exclusion criteria. If a subject meets any of the exclusion criteria marked with an asterisk (*), the Day 1 visit may be rescheduled for a time when these criteria are no longer met. 1. Subject is currently participating or has participated in a study with an investigational compound or device within 4 weeks of expected first dose of PR5I/vaccine control(s). 2. Subject's parent(s)/legal representative plan to enroll the subject in another clinical study during the present study period. 3. Subject has history of congenital immunodeficiency or acquired immunodeficiency (e.g., HIV, splenomegaly). 4. Prior to study entry, subject has received or is expected to receive immunosuppressive agents (e.g., substances or treatments known to diminish immune response such as radiation therapy, antimetabolites, cyclophosphamide, azathioprine, methotrexate, any chemotherapy, cyclosporine, leflunomide [Arava™], TNF-α antagonists, monoclonal antibody therapies [including rituximab (Rituxan™)], intravenous gamma globulin [IVIG], antilymphocyte sera, or other therapy known to interfere with the immune response). 5. Subject has received (a) systemic immunomodulatory steroids (> the equivalent of 2 mg/kg total daily dose of prednisone) since birth, or (b) any dose of systemic immunomodulatory steroids within 7 days prior to entering study, or (c) is expected to require systemic immunomodulatory steroids through the course of the study. Subjects using non-systemic corticosteroids (e.g., topical, ophthalmic, inhaled) will be eligible for vaccination. 6. Subject has a history of leukemia, lymphoma, malignant melanoma, or myeloproliferative disorder. 7. Subject has a known or suspected hypersensitivity to any of the vaccine components or history of a life-threatening reaction to a vaccine containing the same substances as the study vaccines or concomitant study vaccines. XML File Identifier: lbrZgmmIUScxnG4Gy7HUW/wvzcU= Page 37/49 8. Subject has chronic illness that could interfere with study conduct or completion. 9. Subject has received any immune globulin, blood, or blood-derived products since birth. 10. Subject has received a dose of monovalent hepatitis B vaccine or hepatitis B based combination vaccine prior to study entry. 11. Subject has received, prior to enrollment, vaccination with any acellular pertussis (DTaP) or whole cell pertussis (DTwP) based combination vaccines, Haemophilus influenzae type b conjugate, poliovirus, pneumococcal conjugate or pneumococcal polysaccharide, rotavirus vaccine, or combination thereof. 12. *Subject has had a febrile illness within 24 hours prior to enrollment or a rectal temperature ≥38.0°C at Visit 1. 13. *Subject has been vaccinated with any non-study vaccine (e.g. inactivated, conjugated or live virus vaccine) within 30 days prior to enrollment, except for inactivated influenza vaccine, which is permitted 14 days or more prior to enrollment. 14. Subject has a coagulation disorder contraindicating intramuscular (IM) vaccination. 15. Subject has clinically significant findings on review of systems (by medical history) determined by the investigator or sub-investigator to be sufficient for exclusion. 16. Subject has developmental delay or neurological disorder (by medical history at study entry). 17. Subject or his/her mother has a medical history of HBsAg seropositivity. 18. Subject has a history of Haemophilus influenzae type b, hepatitis B, diphtheria, tetanus, pertussis, poliomyelitis, rotavirus gastroenteritis, or invasive pneumococcal infection. 19. Subject's parent(s)/legal representative are unlikely to adhere to study procedures, keep appointments, or are planning to relocate during the study. 20. Any contraindication to the concomitant study vaccines |
| 1. Il soggetto sta attualmente partecipando o ha partecipato ad uno studio con un composto o un dispositivo sperimentale nelle 4 settimane precedenti la prima dose prevista di PR5I/vaccino/i di controllo. 2. i Genitori del soggetto o i rappresentanti legali intendono arruolare il soggetto in un altro studio clinico durante questo periodo di studio 3. Il soggetto ha una storia clinica di immunodeficienza congenita o immunodeficienza acquisita (per esempio HIV, splenomegalia). 4. Prima del suo ingresso nello studio, il soggetto ha ricevuto o deve ricevere agenti immunosoppressori (per esempio sostanze o trattamenti che notoriamente diminuiscono la risposta immune così come una terapia a radiazioni, antimataboliti, ciclofosfamide, azatiopriae, metotrexate e qualsiasi terapia chemioterapia, ciclosporina, leflunomide [AravaTM], antagonista TNF-α anticorpi monoclonali [incluso rituximab (RituxanTM)], globulina intravenosa gamma [IVIG] antilinfocite sera, o qualsiasi altra terapia che notoriamente interferisce con la risposta immunitaria). 5. Il soggetto ha ricevuto dalla nascita (a) steroidi immunomodulatori sistemici (> l’equivalente di 2 mg/kg dose totale giornaliera di prednisone) o (b) qualsiasi dose di steroidi immunomodulatori sistemici entro 7 giorni prima di entrare nello studio o (c) si prevede che richiederà steroidi immunomodulatori sistemici durante il corso dello studio. I soggetti che utilizzano corticosteroidi non sistematici (esempio, topici, oftalmici, inalati) saranno eleggibili per la vaccinazione. 6. Il soggetto ha una storia clinica di leucemia, linfoma, melanoma maligno e disturbo mieloproliferativo. 7. Il soggetto ha una ipersensibilità nota o sospetta a uno qualsiasi dei componenti del vaccino o una storia clinica di reazioni a rischio di morte a vaccini contenenti le stesse sostanze dei vaccini di studio o vaccini di studio concomitanti. 8. I soggetti soffrono di malattie croniche che possono interferire con la condotta dello studio o il suo completamento. 9. Il soggetto ha ricevuto qualsiasi immune globulina, sangue o prodotti derivanti dal sangue dalla nascita 10. Il soggetto ha ricevuto una dose del vaccino monovalente epatite b o una combinazione di vaccini per epatite B prima di entrare nello studio 11. Il soggetto ha ricevuto, prima dell’arruolamento, il vaccino a base combinata di Pertosse acellulare (DTaP) o pertosse a cellule totali (DTwP), Influenza Emofiliaca di tipo b coniugata, poliovirus, coniugato pneumococco o prenumococco polisaccaride, vaccino rotavirus o sua combinazione. 12. * Il soggetto ha avuto una malattia febbrile entro le 24 ore prima dell’arruolamento o una temperatura rettale di > 38.0°C alla visita 1. 13. * Il soggetto è stato vaccinato con un vaccino non in studio (esempio inattivo, coniugato o vaccino a virus vivo) entro 30 giorni prima dell’arruolamento, ad eccezione del vaccino influenzale inattivato, che è permesso 14 giorni o più prima dell’arruolamento. 14. Il soggetto ha un disturbo di coagulazione che controindica la vaccinazione intramuscolare (IM). 15. Il soggetto presenta degli accertamenti clinici di revisione sistema (dalla storia clinica) determinati dallo sperimentatore o sub sperimentatore sufficienti per l’esclusione. 16. Il soggetto ha un ritardo di sviluppo o disturbo neurologico (storia clinica o all’ingresso dello studio) 17. Il soggetto o la madre del soggetto ha una storia clinica di sieropositività HBsAg 18. Il soggetto ha una storia clinica di influenza emofiliaca di tipo B, epatite b, difteria, tenato, pertosse, poliomielite, rotavirus gastroenterite, o infezione invasiva pneumococco. 19. I genitori del soggetto/rappresentanti legali non sono disponibili ad aderire alle procedure di studio, a mantenere gli appuntamenti o stanno programmando un trasferimento durante lo studio. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoints for the acceptability hypothesis are vaccine induced antibody responses to all antigens contained in PR5I following the Toddler dose (~12 months). The primary endpoints for the non-inferiority hypothesis are vaccineinduced antibody responses against antigens that are contained in both PR5I and the control vaccine after the Toddler dose (~12 months) as listed in Table 2-3 of the protocol. |
| Gli endpoint primari per l'ipotesi di accettabilità sono i vaccini che inducono la risposta anticorpale a tutti gli antigeni contenuti in PR5I seguendo la dose Toddler dei 12 mesi. Gli endpoint primari per l'ipotesi di non inferiorità sono i vaccini che inducono la risposta anticorpale a tutti gli antigeni contenuti in PR5I seguendo la dose dei 12 mesi, come elencato nella tabella 2-3 del protocollo. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| After the toddler dose (12 months) |
| Dopo la dose Toddler dei 12 mesi |
|
| E.5.2 | Secondary end point(s) |
| The endpoint for the secondary hypothesis testing of non-inferiority and superiority regarding PRP response is the proportion of subjects with anti-PRP level ≥1.0 μg/ml at Postdose 2. The endpoint for the secondary hypothesis testing of non-inferiority regarding antirotavirus IgA is the GMT at Postdose 2 in subjects receiving Rotarix |
| L'endpoint per l'ipotesi secondaria del test di non-inferiorità e superiorità riguardo la risposta PRP è la proporzione di soggetti con livelli anti PRP≥1.0 μg/ml alpostdose 2. L'endpoint per l'ipotesi secondaria del test di non-inferiorità riguardo l'antirotavirus IgA è il GMT al Postdose 2 in soggetti che ricevono Rotarix |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| After the toddler dose (12 months) |
| Dopo la dose Toddler di 12 mesi |
|
| 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 |
| tolerability, immunogenicity |
| tolerabilità, immunogenicità |
|
| 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) | 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 | 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 39 |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 33 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 33 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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