Post Authorization Efficacy and Safety Study (PAES) to Confirm and Collect More Clinical Data of Buccalin® Tablets In the Prophylaxis of Recurrent Lower Respiratory Tract Infections (RLRTIs). (BUC-01-23)

Randomized, Double Blind, Placebo Controlled, Two-Arms, Multicenter, Post Authorization Efficacy and Safety Study (PAES) to Confirm and Collect More Clinical Data of Buccalin® Tablets In the Prophylaxis of Recurrent Lower Respiratory Tract Infections (RLRTIs).

The goal of this clinical trial is to assess if BUCCALIN® works In the Prophylaxis of Recurrent Lower Respiratory Tract Infections (RLRTIS). It will also evaluate the safety of BUCCALIN®.

The primary aim is to reduce the number of infection episodes in the treatment period (12 months) in the BUCCALIN® group versus the Placebo group.

Patients diagnosed with RLRTIS will be screened for enrolment. Patients will be requested to provide informed consent before the start of the study related assessments.

Eligible patients who meet the study inclusion and exclusion criteria will be randomized with a 1:1 ratio allocation to the 2 treatment groups.

Researchers will compare BUCCALIN® (gastro-resistant tablets) to a placebo (gastro-resistant tablets containing only excipients) to treat RLRTIS.

Patients who participate in the study will perform several study visits divided as reported below:

• Run-in phase (12 months): patients will not receive any treatment. This phase is designed to increase adherence to the study and reduce loss to follow-up in the clinical trial. During this phase, patients should experience ≥ 2 episodes of RTIs to be eligible for the Treatment period.
• Treatment period (12 months): patients will receive BUCCALIN® or Placebo treatment for 12 consecutive months (3 days per month, posology as per authorized SmPC).
• Follow-up period (12 months): patients will not receive any treatment. This phase is designed to observe how patients respond to treatments.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Infection; Lower Respiratory Tract Infection (LRTI)
• Intervention / Treatment: Drug: BUCCALIN®; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Silvana Lonetti; Phone Number: +39 0384 8071; Email: s.lonetti@sit-farmaceutici.com

Study Locations

• Italy
  • Alessandria, Italy
    • Active, not recruiting
    • AOU Ss. Antonio E Biagio E C.Arrigo
  • Catania, Italy
    • Active, not recruiting
    • AOU Policlinico G. Rodolico-San Marco
  • Milan, Italy
    • Active, not recruiting
    • ASST Grande Ospedale Metropolitano Niguarda
  • Milan, Italy
    • Recruiting
    • ASST Santi Paolo e Carlo
  • Milan, Italy
    • Active, not recruiting
    • Asst Fatebenefratelli Sacco
  • Milan, Italy
    • Active, not recruiting
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
  • Milan, Italy
    • Active, not recruiting
    • Humanitas Mirasole S.p.A
  • Roma, Italy
    • Active, not recruiting
    • AOU Policlinico Tor Vergata
  • Sassari, Italy
    • Recruiting
    • AOU di Sassari
• North Macedonia
  • Skopje, North Macedonia
    • Recruiting
    • University clinic for infectious diseases and febrile conditions, Medical Faculty, Ss Cyril and Methodius University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients willing and able to provide voluntary informed consent and to follow protocol requirements.
2. Male or females from 18 to 99 years old, (Adult, Older Adult).

3. Patients with Recurrent LRTIs including tracheitis, tracheobronchitis, acute bronchitis and exacerbations of chronic lung disease (asthma and/or COPD and/or bronchiectasis), who present with both of the following:

   a) ≥2 episodes within 12 months prior to the run-in period based on patient reported medical history (to access the run-in period) b) ≥2 episodes during the run-in period documented by appropriate microbiological diagnostic test (to access the treatment period)

4. Patients:

   1. not vaccinated or

   2. vaccinated against the most common pathogens for respiratory infectioan (within 12 months prior to the run-in period or during the run-in period, but not during the treatment period)*:

      - Anti-pertussis vaccination

      - Covid-19 vaccination

      - Respiratory Syncytial Virus vaccination

      - Influenza vaccination

      - Pneumococcal vaccination

      * Patients vaccinated with other types of vaccines that have no effect on the lower respiratory tract (e.g. hepatitis b vaccination, shingles/herpes zoster vaccination, papilloma virus vaccine), in addition to the ones listed above, may also be included.

Exclusion Criteria:

RUN-IN period

1. Female patient: pregnant, lactating or planning pregnancy (Female of child-bearing potential will undergo urine pregnancy test).
2. Female of potential child-bearing that does not use at least one effective contraceptive method for the entire study.
3. Contraindication or known hypersensitivity to the active ingredients of bacterial lysates or any excipients listed in the ingredients.
4. Pneumonia (based on the EMA Referral Procedure EMEA/H/A-31/1465).
5. Known history of tuberculosis and/or cystic fibrosis.
6. Known history of immunodeficiency diseases (e.g., HIV infection, AIDS, or any type of congenital or iatrogenic immune deficiency, including IgA deficiency).
7. Severe heart failure (NYHA class III and IV).
8. Haematologic diseases including severe anaemia (defined according to the National Cancer Institute as Hemoglobin < 8.0 g/dL).
9. Renal failure (eGFR < 30 mL/min).
10. History of known liver damages defined by the METAVIR classification (F1-F4)*.
11. Malignancies with a remission period of < 5 years.
12. Wheezing documented to be caused by gastroesophageal reflux**.
13. Patient legally or mentally incapacitated unable to give informed consent for the participation in this study.
14. Patient who is unable or unwilling to comply with the appointments or with all the requirements of the Protocol.

15. History of autoimmune diseases and acute intestinal infections, as reported in Buccalin® SmPC.

    • This criterion only applies to patients with known liver disease who can produce valid fibroscan and/or biopsy results and bring them for demonstration.

      • The criterion can only be applied if the patient presents clinically reliable documentation that the wheezing is not due to a lung disease (i.e. gastroscopy).

TREATMENT period

1. Female patient: pregnant, lactating or planning pregnancy (Female of child-bearing potential will undergo urine pregnancy test).
2. Female of potential child-bearing that does not use at least one effective contraceptive method for the entire study.
3. Contraindication or known hypersensitivity to the active ingredients of bacterial lysates or any excipients listed in the ingredients.
4. Pneumonia (based on the EMA Referral Procedure EMEA/H/A-31/1465).
5. Known history of tuberculosis and/or cystic fibrosis.
6. Known history of immunodeficiency diseases (e.g., HIV infection, AIDS, or any type of congenital or iatrogenic immune deficiency, including IgA deficiency).
7. Severe heart failure (NYHA class III and IV).
8. Haematologic diseases including severe anaemia (defined according to the National Cancer Institute Hemoglobin < 8.0 g/dL).
9. Renal failure (eGFR < 30 mL/min).
10. History of known liver damages defined by the METAVIR classification (F1-F4)*.
11. Malignancies with a remission period of < 5 years.
12. Injection or oral administration of steroids within 4 weeks prior to randomization**.
13. Use of immunosuppressants, immunostimulants, or gamma globulins within 6 months prior to randomization.
14. Previous use within 6 months prior to randomization or ongoing use of bacterial lysates.
15. Any major surgery within the last 3 months prior to randomization.
16. Wheezing documented to be caused by gastroesophageal reflux***.
17. Patient legally or mentally incapacitated unable to give informed consent for the participation in this study.
18. Patient who is unable or unwilling to comply with the appointments or with all the requirements of the Protocol.

19. History of autoimmune diseases and acute intestinal infections, as reported in Buccalin® SmPC.

    • This criterion only applies to patients with known liver disease who can produce valid fibroscan and/or biopsy results and bring them for demonstration.

      • In these instances, patients may undergo a washout period of 4 weeks to qualify for the treatment period.

        • The criterion can only be applied if the patient presents clinically reliable documentation that the wheezing is not due to a lung disease (i.e. gastroscopy).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: BUCCALIN® gastro-resistant tablets; mixture of Streptococcus pneumoniae I, II, III, Streptococcus agalactiae, Staphylococcus aureus, Haemophilus influenzae	Drug: BUCCALIN®; Gastro-resistant tablets (mixture of Streptococcus pneumoniae I, II, III, Streptococcus agalactiae, Staphylococcus aureus, Haemophilus influenzae). The recommended dosage is 1 tablet on day 1, 2 tablets on day 2, and 4 tablets on day 3 and should be taken in the morning on an empty stomach.
Placebo Comparator: Placebo; gastro-resistant tablets containing only excipients	Other: Placebo; Gastro-resistant tablets containing only excipients). The recommended dosage is 1 tablet on day 1, 2 tablets on day 2, and 4 tablets on day 3 and should be taken in the morning on an empty stomach.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
RLRTIs Episodes: Reduction in the number of infection episodes in the treatment period (12 months) in the Buccalin® group versus the Placebo group.	From the enrollment to the end of the treatment at 24 months

Collaborators and Investigators

• Sponsor: Laboratorio Farmaceutico SIT srl

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: December 3, 2024
• First Submitted That Met QC Criteria: December 12, 2024
• First Posted (Actual): December 16, 2024

Study Record Updates

• Last Update Posted (Actual): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Respiratory Tract Infections; buccalin
• Other Study ID Numbers: BUC-01-23; 2024-512937-34-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No