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).
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 224
- 试验地点
- 10
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 3 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Children of both genders aged from 3 to 12 years.
- •Written informed consent obtained from the parents/legally authorized representatives
- •Written assent obtained from the subject from 7 years
- •Subject presenting with a susceptibility to respiratory tract infections according to the investigator
- •No respiratory tract infection within 15 days before the randomization visit
- •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.
- •A cooperative attitude and ability to correct use of PMBL® tablet.
排除标准
- •Subject treated with bacterial lysates within the previous 6 months prior to V1 or ongoing treatment.
- •Body temperature ≥ 37.5°C at the randomization visit.
- •Pregnant/Lactating female or with sexual activity without hormonal contraception, intrauterine device or barrier methods.
- •Primary or secondary immunodeficiency, cystic fibrosis, bronchiectasis, alpha-1 antitrypsin deficiency, malignancy, endocrinological diseases or other chronic respiratory diseases, except asthma and allergic rhinitis.
- •Known sensitivity to the components of study medication.
- •Any major surgery within the last 3 months prior to study enrolment or planned to occur within the duration of study.
- •Treatment with the following medications:
- •Injection or oral administration of steroids within 4 weeks prior to study enrolment.
- •Previous and/or concomitant immunosuppressants, immunostimulants, allergen-immunotherapy or gamma globulins within 6 months prior to study enrolment.
- •Inability to understand or comply with study procedures or with study treatment intake.
- •Subject participating in another interventional clinical study at the time of screening visit.
研究组 & 干预措施
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.
干预措施: Bacterial Lysates (Drug)
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.
干预措施: Placebo (Drug)