Confirming and collecting more data on Buccalin® tablets for preventing recurrent lower respiratory tract infections

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).

This trial will test whether Buccalin® gastro-resistant tablets can prevent recurrent lower respiratory tract infections in adults who have had multiple infections.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 240 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: Laboratorio Farmaceutico SIT srl (industry)
• Locations: 10 sites (Alessandria and 9 other locations)
• Trial ID: NCT06736288 on ClinicalTrials.gov

What this trial studies

This Phase 4, post-authorization randomized study compares Buccalin® gastro-resistant tablets to matching placebo in adults with recurrent lower respiratory tract infections. Eligible participants complete a 12-month run-in period with no study treatment to document infection frequency, then are randomized 1:1 to Buccalin® or placebo for a 12-month treatment period. The trial tracks the number of infection episodes during treatment and monitors safety and adverse events. Study visits occur at participating hospitals in Italy and include microbiological confirmation of infection episodes.

Who should consider this trial

Good fit: Adults aged 18–99 with recurrent LRTIs who had at least two episodes in the year before the run-in and at least two microbiologically documented episodes during the 12-month run-in, and who can provide informed consent, are the intended participants.

Not a fit: Patients without recurrent LRTIs (fewer than two episodes) or whose symptoms are due to non-infectious causes are unlikely to benefit from this preventive treatment.

Why it matters

Potential benefit: If successful, Buccalin® could reduce the number of respiratory infection episodes over 12 months in adults with recurrent LRTIs.

How similar studies have performed: Previous trials of mucosal prophylactic agents for recurrent respiratory infections have produced mixed results, so additional confirmatory data are needed.

Eligibility criteria

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).

Where this trial is running

Alessandria and 9 other locations

• AOU Ss. Antonio E Biagio E C.Arrigo — Alessandria, Italy (ACTIVE_NOT_RECRUITING)
• AOU Policlinico G. Rodolico-San Marco — Catania, Italy (ACTIVE_NOT_RECRUITING)
• ASST Fatebenefratelli Sacco — Milan, Italy (ACTIVE_NOT_RECRUITING)
• ASST Grande Ospedale Metropolitano Niguarda — Milan, Italy (ACTIVE_NOT_RECRUITING)
• ASST Santi Paolo e Carlo — Milan, Italy (RECRUITING)
• Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico — Milan, Italy (ACTIVE_NOT_RECRUITING)
• Humanitas Mirasole S.p.A — Milan, Italy (ACTIVE_NOT_RECRUITING)
• AOU Policlinico Tor Vergata — Roma, Italy (ACTIVE_NOT_RECRUITING)
• AOU di Sassari — Sassari, Italy (RECRUITING)
• University clinic for infectious diseases and febrile conditions, Medical Faculty, Ss Cyril and Methodius University — Skopje, North Macedonia (RECRUITING)

Study contacts

• Study coordinator: Silvana Lonetti

Conditions: Respiratory Infection, Lower Respiratory Tract Infection