Prevention With Ismigen of RTIs in Kids (PIRTIK)

A Randomized Double-blind Placebo-controlled Study to Demonstrate the Efficacy of PMBL® Sublingual Tablets in Reducing the Incidence of Respiratory Tract Infections in Children Aged 3-12 Years (PIRTIK).

Although the efficacy of PMBL® sublingual tablets is evident to most prescribers, the clinical studies available to demonstrate the efficacy of this bacterial lysate in preventing recurrent respiratory tract infections have undeniable methodological biases. To demonstrate the efficacy of PMBL® in the pediatric population without questionable bias, a randomized double-blind Placebo-controlled study will be conducted: one arm of children presenting with a risk of recurrent respiratory tract infections will be treated with PMBL® for a 3-month period, 10 days per months during the fall-winter whereas subjects of the Placebo arm will receive sublingual tablet indistinguishable from PMBL® but without active ingredients. Both groups of subjects will be followed for four additional months. To improve the accuracy of data and the tracking of respiratory tract infections (RTI), a diary will be provided to each subject, allowing them to report the event as soon as it occurs. If necessary, a visit may be planned to enable the investigator to assess the event accurately.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Children; Respiratory Tract Infections (RTI)
• Intervention / Treatment: Drug: Bacterial Lysates; Drug: Placebo

Detailed Description

Respiratory tract infections (RTIs) are the leading cause of acute disease incidence worldwide that affect people of all ages. They are usually caused by viral pathogens, the most common of which including rhinoviruses, coronaviruses, adenoviruses, respiratory syncytial virus and influenza viruses. Bacterial pathogens can also cause RTIs, but they are less common. Various studies show the seasonality of RTIs. Influenza tends to occur in late autumn and winter, while other RTIs have a much more diffuse occurrence throughout the year. Although RTIs are usually not life-threatening, they significantly decrease quality of life and represent a substantial proportion of healthcare visits, mainly in women and young children, contributing to a financial burden on society.

Ismigen® (Polyvalent Mechanical Bacterial Lysate; PMBL) which is manufactured by mechanical lysis is currently authorized in two EU Member States (MS), Italy and Poland, where Lallemand Pharma Europe is the Marketing Authorization Holder (MAH) as sublingual tablets for the prophylaxis of recurrent RTI in adults. It is authorized in Poland in children from 3 years of age.

On 27 June 2019, the European Medicines Agency (EMA) recommended that bacterial lysates-containing medicinal products authorized for respiratory conditions should only be used for the prevention of recurrent respiratory tract infections, with the exception of pneumonia. This followed a review in which EMA's human medicines committee (CHMP) considered the results of clinical studies, data on side effects reported with these medicines, and advice from an expert group on infectious diseases. Although data are limited, the review found some evidence of effectiveness of bacterial lysates in the prevention of recurrent RTI together with a safety profile in line with what is expected for this type of product. The CHMP therefore recommended that use of bacterial lysates for prevention can continue, but the companies must provide further data on safety and effectiveness by Q1 2026 through the conduct of phase IV double-blind, multicenter, RCTs in this indication.

The present study is a Post-Authorization Efficacy Study (PAES) designed to demonstrate that PMBL® sublingual tablet used according to the SmPC instructions can reduce the incidence of respiratory tract infections in children 3 to 12 years old during the fall and winter period when compared to a matched Placebo.

• Study Type: Interventional
• Enrollment (Estimated): 224
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Bernard GOUT, PharmD, PhD; Phone Number: +33776583905; Email: bgout@pharmndev.ch

Study Locations

• Poland
  • Bialystok, Poland
    • Research Site
  • Bydgoszcz, Poland
    • Research Site
  • Krakow, Poland
    • Research Site
  • Krąków, Poland
    • Research Site
  • Lublin, Poland
    • Research Site
  • Oświęcim, Poland
    • Research Site
  • Poznan, Poland
    • Research Site
  • Tarnów, Poland
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Children of both genders aged from 3 to 12 years.
2. Written informed consent obtained from the parents/legally authorized representatives
3. Written assent obtained from the subject from 7 years
4. Subject presenting with a susceptibility to respiratory tract infections according to the investigator
5. No respiratory tract infection within 15 days before the randomization visit
6. All girls of childbearing potential have a negative pregnancy urine testing at randomization visit and are informed and their parents as well of the requirement for contraception during the study.
7. A cooperative attitude and ability to correct use of PMBL® tablet.

Exclusion Criteria:

1. Subject treated with bacterial lysates within the previous 6 months prior to V1 or ongoing treatment.
2. Body temperature ≥ 37.5°C at the randomization visit.
3. Pregnant/Lactating female or with sexual activity without hormonal contraception, intrauterine device or barrier methods.
4. Primary or secondary immunodeficiency, cystic fibrosis, bronchiectasis, alpha-1 antitrypsin deficiency, malignancy, endocrinological diseases or other chronic respiratory diseases, except asthma and allergic rhinitis.
5. Known sensitivity to the components of study medication.
6. Any major surgery within the last 3 months prior to study enrolment or planned to occur within the duration of study.

7. Treatment with the following medications:

   1. Injection or oral administration of steroids within 4 weeks prior to study enrolment.
   2. Previous and/or concomitant immunosuppressants, immunostimulants, allergen-immunotherapy or gamma globulins within 6 months prior to study enrolment.
8. Inability to understand or comply with study procedures or with study treatment intake.
9. Subject participating in another interventional clinical study at the time of screening visit.

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: PMBL® sublingual tablet; Ismigen® (Polyvalent Mechanical Bacterial Lysate; PMBL) is a sublingual tablet marketed by Lallemand Pharma Europe. Each tablet contains: Lyophilised bacterial lysate 50 mg; Excipients q.s. 250mg The posology of Ismigen® for paediatric population (from 3 years of age) is one tablet per day before food, to be dissolved under the tongue. Use for ten consecutive days per month, over a period of 3 months.	Drug: Bacterial Lysates; 3-month period, 10 days per months during the fall-winter; Other Names: PMBL® sublingual tablet; ISMIGEN®
Placebo Comparator: Placebo; The comparator is a sublingual tablet, indistinguishable from the investigational product. Each tablet of placebo comparator has the same composition as the investigational medicinal product being tested (with the exception of the active substance, which is replaced by glycine (7 mg)). Posology, instructions for use, contraindications, precautions of use and labelling are identical to those for Ismigen®. The posology of Placebo is one tablet per day before food, to be dissolved under the tongue. Use for ten consecutive days per month, over a period of 3 months.	Drug: Placebo; 3-month period, 10 days per months during the fall-winter

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The total number of RTIs experienced by each subject throughout the 7-month study period (3-month treatment + 4-month follow-up).	Rate of Respiratory Tract Infections (RTIs): the number of RTIs experienced by a subject throughout the study (3 month-treatment period and 4 month-follow-up) will be assessed.	Throughout the 7-month study period (3-month treatment + 4-month follow-up).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean duration in days per RTI during the overall study period.	Estimated treatment effect from MMRM with 95% CI.	Throughout the 7-month study period (3-month treatment + 4-month follow-up).
Number of days with respiratory tract infections during the overall study period	Negative binomial or Poisson regression with 95% CI.	Throughout the 7-month study period (3-month treatment + 4-month follow-up).
Number of days of antibiotics use during the overall study period	Estimated incidence rate ratio (IRR) using negative binomial regression (or Poisson if appropriate) with 95% CI.	Throughout the 7-month study period (3-month treatment + 4-month follow-up).
Total number of workdays lost by parents due to their child's respiratory infections during the overall study period.	Total number of workdays lost by children's parents due to the child's respiratory infections during the overall study period (cumulative days) For each endpoint: mean (SD), median (IQR), and cumulative counts by treatment arm; primary between-group effect presented as an incidence rate ratio (IRR) with 95% CI (PMBL® vs placebo). Absolute mean difference and 95% CI will also be provided for interpretability	Throughout the study (3 month-treatment period and 4 month-follow-up)
Number of physician consultations due to RTI or related complications.	Number of physician consultations due to RTI or related complications during the overall study period (count) For each endpoint: mean (SD), median (IQR), and cumulative counts by treatment arm; primary between-group effect presented as an incidence rate ratio (IRR) with 95% CI (PMBL® vs placebo). Absolute mean difference and 95% CI will also be provided for interpretability	Throughout the study (3 month-treatment period and 4 month-follow-up)
Number of antibiotic treatments (courses) for a respiratory event during the overall study period.	Number of antibiotic treatments courses for a respiratory event during the overall study period (count of courses) For each endpoint: mean (SD), median (IQR), and cumulative counts by treatment arm; primary between-group effect presented as an incidence rate ratio (IRR) with 95% CI (PMBL® vs placebo). Absolute mean difference and 95% CI will also be provided for interpretability	Throughout the study (3 month-treatment period and 4 month-follow-up)
Number of subjects with (serious) adverse event and (serious) adverse drug reaction	Descriptive statistics: number and proportion of subjects experiencing events by type and severity Number and type of AEs, SAEs, and SARs during the study period	Throughout the study (3 month-treatment period and 4 month-follow-up)

Collaborators and Investigators

• Sponsor: Lallemand Pharma AG
• Investigators: Principal Investigator: Andrzej EMERYK, MD, PhD, University Children Hospital, Lublin, Poland

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: May 5, 2026
• First Submitted That Met QC Criteria: May 5, 2026
• First Posted (Actual): May 11, 2026

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Incidence; Recurrent Respiratory Tract Infections; Respiratory Tract Infections (RTI); Bacterial Lysates; PMBL® sublingual tablets; Ismigen
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Respiratory Tract Infections; Biological Products; Complex Mixtures; Broncho-Vaxom; Bacterial Lysates
• Other Study ID Numbers: LPI-2501; 2025-524212-11-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No