Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
760
Countries
1
Sites
4
Respiratory sincizial (RSV) bronchiolitis
To compare the incidence rate of overall respiratory morbidity in otherwise healthy (neonate who does not display any major short-or-long-term morbidity related to prematurity) preterm babies 29 +0 -35+6 wGA exposed to prophylaxis with palivizumab (Group A) vs infants 29+0 - 35+6 wGA NOT exposed to prophylaxis with p…
Key facts
- Sponsor
- Azienda Sanitaria Locale Della Provincia Di Biella
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Respiratory Tract Diseases [C08]
- Trial duration
- 12 Jun 2020 → 22 May 2025
- Decision date (initial)
- 2024-08-07
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- AIFA Bandi per la ricerca indipendente
External identifiers
- EU CT number
- 2024-515418-41-00
- EudraCT number
- 2018-002980-25
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy
To compare the incidence rate of overall respiratory morbidity in otherwise healthy (neonate who does not display any major short-or-long-term morbidity related to prematurity) preterm babies 29 +0 -35+6 wGA exposed to prophylaxis with palivizumab (Group A) vs infants 29+0 - 35+6 wGA NOT exposed to prophylaxis with palivizumab (Group B)
Secondary objectives 2
- To evaluate the difference of RSV-related hospitalization due to low respiratory infection during the first RSV-season (November 1st-March 31th) between Group A and Group B.
- To evaluate direct and indirect costs related to respiratory sequelae in both groups. The following information for an accurate cost evaluation will be collected: lenght of hospitalizations; need for Mechanical Ventilation and other support therapies; Intensive Care Unit admission and length of stay; medical specialistic visits; drugs (type, dosage and therapy duration); diagnostic exams, loss of working days for parents due to child illness.
Conditions and MedDRA coding
Respiratory sincizial (RSV) bronchiolitis
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | PT | 10038718 | Respiratory syncytial virus bronchiolitis | 100000004862 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Otherwise healthly (neonate who does not display any major short-or long-term morbidity related to prematurity) preterm infants 29+0 - 35+6 wGA (male and female)
- Younger than 6 months of age at the beginning of the RSV season (November 1st)
- Written IC obtained from parents/legal guardian
Exclusion criteria 8
- Children HIV+
- Children with neoplasia
- Children with a known cardiac anomaly
- Children with Down syndrome
- Children with severe congenital disorders
- Children who had physician-diagnosed wheeze before the start of the RSV season
- High risk for severe course of RSV infection: children with Bronshopulmonary Dysplasia, children with neuromuscolar impairment, children with cystic fibrosis, children with diaphragmatic hernia and other severe congenital respiratory disorders
- Documented hypersensitivity to the drug or to any of its excipients, ot to other humanized monoclonal antibodies
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Overall respiratory morbidity (composite primary endpoint), whose definition is: a) LRTIs by any pathogen (including, but not limited to RSV); b) recurrent wheezing (quantified as presence of wheezing days and/or need for use of antiwheezing drugs ) +/- asthma
Secondary endpoints 3
- Difference of number of RSV-related hospitalizations due to low respiratory tract infection during the first RSV-season (November 1st- March 31th) between Group A and Group B.
- Direct costs in terms of difference of health resources used by Group A and Group B respectively and related to: lenght of hospitalizations(days);mechanical ventilation and other support therapies(type, number, duration);Intensive Care Unit admission and lenght of stay(days);outpatient visits(type and number of specialistic visits);drugs(type, dosage and therapy duration);diagnostic tests(type and number).Costs for resources used will be calculated using National Health Service tariffs
- Indirect costs in terms of loss of working days for due to child illness
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Synagis 50 mg/0.5 ml solution for injection
PRD8843597 · Product
- Active substance
- Palivizumab
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INJECTION
- Max daily dose
- 15 mg/kg milligram(s)/kilogram
- Max total dose
- 15 mg/Kg milligram(s)/kilogram
- Max treatment duration
- 5 Month(s)
- Authorisation status
- Authorised
- ATC code
- J06BB16 — PALIVIZUMAB
- Marketing authorisation
- EU/1/99/117/003
- MA holder
- ASTRAZENECA AB
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Azienda Sanitaria Locale Della Provincia Di Biella
- Sponsor organisation
- Azienda Sanitaria Locale Della Provincia Di Biella
- Address
- Via Dei Ponderanesi 2
- City
- Ponderano
- Postcode
- 13875
- Country
- Italy
Scientific contact point
- Organisation
- Azienda Sanitaria Locale Della Provincia Di Biella
- Contact name
- Paolo Manzoni
Public contact point
- Organisation
- Azienda Sanitaria Locale Della Provincia Di Biella
- Contact name
- Francesco D'Aloia
Third parties 2
| Organisation | City, country | Duties |
|---|---|---|
| Consorzio Per Valutazioni Biologiche E Farmacologiche ORG-100006471
|
Bari, Italy | On site monitoring, Code 12, Code 8 |
| Istituto Di Fisiologia Clinica Del CNR Officina Farmaceutica Dell'Istituto Di Fisiologia Clinica ORG-100021636
|
Pisa, Italy | Code 10, Data management |
Locations
1 EU/EEA country · 4 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ended | 760 | 4 |
| Rest of world | — | 0 | — |
Investigational sites
Universita Degli Studi Di Padova
Dipartimento di Salute della Donna e del Bambino (DSB), Via Nicolo' Giustiniani 3, 35128, Padova
Ospedale degli Infermi di Biella
Dipartimento Materno Infantile, Via dei Ponderanesi 2, 13875, Ponderano
Azienda Ospedaliera Universitaria Gaetano Martino Messina
UOC di Patologia e Terapia Intensiva Neonatale, Via Consolare Valeria N 1, 98124, Messina
Istituto Di Ricovero E Cura A Carattere Scientifico Materno Infantile Burlo Garofolo
S.C. Neonatologia e Terapia Intensiva, Via Dell' Istria 65/1, 34137, Trieste
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2020-06-12 | 2020-11-03 | 2024-02-16 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Serious breaches 1 · Art. 52 CTR
Serious breach SB-92974
- Sponsor became aware
- 2020-04-05
- Date of breach
- 2020-04-05
- Submission date
- 2025-08-04
- Member states concerned
- Italy
- Categories
- Protocol
- Areas impacted
- Data reliability or robustness
- Benefit-risk balance changed
- No
- Description
- During the pandemic period, the investigator found it necessary to make some deviations from the original study protocol in order to address the unprecedented challenges that the health and epidemiological situation was presenting. In particular, it became evident that the COVID-19 pandemic could put the health of many patients, especially children, at risk of viral respiratory infections, such as respiratory syncytial virus (RSV). To ensure adequate protection for all patients involved in the study and to limit the risk of RSV infection, the investigator decided to force randomisation by administering the Investigational Medicinal Product (IMP) to almost all participants. This decision was taken with the intention of ensuring effective and timely prophylaxis, thus helping to avert a possible collapse of health facilities already overburdened by the pandemic. Moreover, during this period, many patients did not have the opportunity to receive adequate care from their paediatricians, due to the limited accessibility of primary health services and the high demand for medical care related to the pandemic. Consequently, hospitalisation was necessary to ensure adequate monitoring and treatment. The approach adopted by the investigator, although not in accordance with the study protocol, was dictated by reasons of public safety and the need to protect the health of patients in an extremely critical, unpredictable, unexpected context that could not be dealt with by ordinary means. It is important to note that no SAEs were recorded in the last reporting period; in fact, all the SAEs listed in Table 2 occurred before 2022 and were already reported in previous DSURs.
- Sponsor actions
- This deviation did not have any negative impact on patient safety; on the contrary, it significantly helped mitigate health risks for the participants during a critical epidemiological situation.
The impact on the integrity of the study data, resulting from the suspension of randomization, was addressed through the revision of the Statistical Analysis Plan (SAP), which includes specific sensitivity analyses to assess the effect of the deviation.
The study site had to implement a protocol deviation/correction during the period from November 2020 to March 2022 due to the COVID-19 pandemic. Specifically, to protect the vulnerable population involved (preterm infants), randomization was temporarily suspended.
The Principal Investigator (PI) and the sponsor deemed it clinically and ethically unacceptable to assign subjects to the placebo arm (as per the protocol, which provides for a 1:1 randomization between palivizumab and placebo), in order to reduce the risk of respiratory syncytial virus (RSV) infection and the resulting need for hospitalization in pediatric wards, including intensive care units.
Measures implemented by the CRA:
• The deviation was documented in the study management system and comprehensively detailed in the monitoring reports.
• The CRA discussed the deviation with the Principal Investigator (PI) and the study sponsor.
• The site staff was trained and reminded to promptly document and report any extraordinary clinical decisions that could lead to protocol deviations.
Measures implemented by the PI/Sponsor:
• The sponsor did not repeat the deviation and incorporated the occurrence into the revision of the statistical analysis plan.
| Organisation | City | Country | Type |
|---|---|---|---|
| Ospedale degli Infermi di Biella | Ponderano | Italy | Sponsor (non commercial) |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| Statistical Report SUM-107413
|
2025-11-20T16:20:44 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| PRESERV LAYPERSON SUMMARY OF RESULTS | 2025-11-20T16:19:23 | Submitted | Laypersons Summary of Results |
Documents 9 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | PRESERV_LayPerson summary of Results | 1 |
| Protocol (for publication) | D1_Protocol_2024-515418-41-00_Redacted | 4.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_ICF_parents | 4.0 |
| Subject information and informed consent form (for publication) | L1_ICF_parents_TC | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS | 1.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Synagis-palivizumab | 1 |
| Summary of results (for publication) | SR_PRESERV 20251105 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2024-515418-41-00_Redacted | 2.0 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-06-25 | Italy | Acceptable 2024-07-29
|
2024-08-07 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-10-21 | Italy | Acceptable | 2024-12-02 |