Efficacy and Safety of Polyoxidonium, Nasal and Sublingual Spray, 6 mg/ml in Children Aged 1-12 Years With ARI

Study Overview
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Brief Summary
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The purpose of this study is is to demonstrate superiority of Polyoxidonium, nasal and sublingual spray, 6 mg/ml over placebo in children aged from 1 to 12 years with acute respiratory viral infections. This is a multicenter prospective, randomized, double-blind, placebo-controlled, parallel-group phase 3 study.

Detailed Description
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This is a multicenter prospective, randomized, double-blind, placebo-controlled, parallel-group phase 3 study to evaluate efficacy of Polyoxidonium spray 6 mg/ml on acute respiratory viral infections symptoms in children population. A study will last for 13 days (maximum) for each participant and will include 6 visits: Day 0 (Screening), Day 1, Day 3, Day 5, Day 8 ±1, Day 12 ±1. Express tests will be performed at the screening visit to exclude subjects with influenza or streptococcal infection. All eligible subjects will be treated with Polyoxidonium spray 6 mg/ml or placebo spray for 7 days. Clinical blood and urine tests will be performed at days 0 and 8 ±1. Symptom Assessment Scale (SAS) will be filled in at days 0, 1, 3, 5 and 8 ±1. Integrative Medicine Outcome Scale (IMOS) will be filled in by investigator and a parent/adopter at day 8 ±1. Adverse events information will be collected at days 1, 3, 8 ±1 and 12 ±1.

Official Title
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A Multicenter Prospective, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Polyoxidonium, Nasal and Sublingual Spray, 6 mg/ml in Children Aged From 1 to 12 Years With ARI (Acute Respiratory Infection)

Conditions
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Acute Respiratory Infection

Intervention / Treatment
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* Drug: Polyoxidonium 6 mg/ml
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients aged 1 to 12 years Diagnosis of acute respiratory viral infection [International Classification of Diseases (10-th revision) codes: Acute nasopharyngitis [common cold], J02 Acute pharyngitis, J02.9 Acute pharyngitis, unspecified, J04 Acute laryngitis and tracheitis, J04.0 Acute laryngitis, J04.1 Acute tracheitis, J04.2 Acute laryngotracheitis, J06 Acute upper respiratory infections of multiple and unspecified sites, J06.0 Acute laryngopharyngitis, J06.9 Acute upper respiratory infection, unspecified] confirmed by physical examination: axillary temperature ≥ 37,0°C (measured at the moment of physical examination) and Symptoms Assessment Scale total score ≥5 points (not less than 3 of which should be related to ear, or nose, or throat, or upper respiratory tract affection symptoms). Less than 24 hours from the onset of disease (first respiratory viral infection symptoms) Informed consent signed by parent/adopter, or a child (applicable for children aged > 10 years) Exclusion Criteria: Suspicion on pneumonia, bacterial infection (including meningitis, sepsis, otitis media, sinusitis, sinusitis, urinary tract infection etc.) or a condition that requires antibacterial therapy from the first day of treatment. Suspicion on other diseases that may simulate acute respiratory viral infection at the moment of onset (other infectious diseases, flu-like syndrome in system collagen and other diseases). Positive express test for influenza or streptococcal infection. Clinical signs of serious acute respiratory viral infection, which requires hospitalization (fever ≥ 40°C, sings of airway obstruction, significant hemodynamic or neurological disorders). History of primary or secondary immunodeficiency. Cancer. Acute infectious and non-infectious diseases (except acute respiratory viral infection), exacerbation or decompensation of chronic diseases (diabetes mellitus, infantile cerebral paralysis, cystic fibrosis, primary ciliary dyskinesia, bronchopulmonary dysplasia, malformations of upper respiratory tract,ears, nose, or throat) which may affect an ability of patient to participate in study. Saccharase/isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption. History of allergy/hypersensitivity to any component of the study drug (including paracetamol, propacetamol hydrochloride). Use of protocol-prohibited medications within 1 month prior to study. Children, who's parents/adopters may fail to follow the protocol procedures and treatment, in investigator's opinion. Participation in other studies within 3 months to screening. Pregnancy. Any other medical or social condition that may interrupt study participation, in investigator's opinion.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Polyoxidonium 6 mg/ml<br>Polyoxidonium 6 mg/ml nasal and sublingual spray - 0,15 mg/kg daily - 7 days. | Drug: Polyoxidonium 6 mg/ml<br>* Nasal and sublingual spray Polyoxidonium 6 mg/ml will be administered at a dose of 0,15 mg/kg daily for 7 days: in children aged from 1 to 2 years - 1 spray sublingually 2 times a day (every 12 hours); in children aged from 2 to 5 years - 1 spray intranasally (in each nasal passage) 2 times a day (every 12 hours; in children aged from 5 to 8 years - 1 spray intranasally (in each nasal passage) 3 times a day (every 8 hours); in children aged from 8 to 12 years - 2 spray intranasally (in each nasal passage) 2 times a day (every 12 hours).<br>* Other names: Polyoxidonium, Nasal and Sublingual Spray, 6 mg/ml;|
| Placebo Comparator: Placebo<br>Placebo, nasal and sublingual spray - 7 days. | Other: Placebo<br>* Placebo nasal and sublingual spray will be administered for 7 days: in children aged from 1 to 2 years - 1 spray sublingually 2 times a day (every 12 hours); in children aged from 2 to 5 years - 1 spray intranasally (in each nasal passage) 2 times a day (every 12 hours; in children aged from 5 to 8 years - 1 spray intranasally (in each nasal passage) 3 times a day (every 8 hours); in children aged from 8 to 12 years - 2 spray intranasally (in each nasal passage) 2 times a day (every 12 hours).<br>* Other names: Placebo, Nasal and Sublingual Spray;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fever Duration (With a Superiority Cut-off Level δ=-0,52 Days) | Normalization of body temperature (axillary body temperature level ≤ 36,9 °C confirmed by two consecutive measurements (morning-evening/evening-morning)) will be considered as the end of fever | Day 8±1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Intoxication Symptoms by 3 Day of Treatment Due to Symptom Assessment Scale (SAS) | A total number of patients (NP) without symptoms due to General intoxication symptoms domain of the Symptom Assessment Scale (SAS) was evaluated. A total number of patients (NP) with mild symptoms due to General intoxication symptoms domain of SAS (1 point according SAS) was evaluated. A total number of patients (NP) with moderate symptoms due to General intoxication symptoms domain of SAS (2 point according SAS) was be evaluated. A total number of patients (NP) with severe symptoms due to General intoxication symptoms domain of SAS (3 point according SAS) was evaluated. Domain General intoxication symptoms includes the following symptoms: altered/decreased activity; altered appetite; unhealthy appearance; altered or interrupted sleep. Each symptom may be graded by the following points: 0 points - absent; 1 point - mild; 2 points - moderate; 3 points - severe. | Day 3 | 
| Number of Patients (NP) Without Nasal Discharge Symptom by 3 and 5 Day of Treatment, Number of Patients (NP) With Mild/Moderate/Severe Nasal Discharge Symptom by 3 and 5 Day of Treatment | Each symptom was graded by the following points: 0 points - absent; 1 point - mild; 2 points - moderate; 3 points - severe. Number of patients (NP) without nasal discharge symptom by 3 and 5 day of treatment (score on the scale 0 point), Number of patients (NP) with mild nasal discharge symptom by 3 and 5 day of treatment (score on the scale 1 points) Number of patients (NP) with moderate nasal discharge symptom by 3 and 5 day of treatment (score on the scale 2 points) Number of patients (NP) with severe nasal discharge symptom by 3 and 5 day of treatment (score on the scale 3 points) | Day 3, Day 5 | 
| Score on Symptoms: Nasal Discharge and Nasal Congestion/Impaired Nasal Airflow Due to Symptom Assessment Scale by 3 and 5 Day of Treatment | Each symptom was graded by the following points: 0 points - absent; 1 point - mild; 2 points - moderate; 3 points - severe. The higher scores mean worse outcome. The maximum score is 3 points, the minimum score is 0 points. | Day 3, Day 5 | 
| Total Score on Symptom Assessment Scale by 3 and 5 Day of Treatment | Symptom Assessment Scale (SAS) consists of 3 domains: Domain General intoxication symptoms (altered/increased activity/dysfunctional behavior; altered appetite or food refusal; unhealthy or alter from common appearance; altered or interrupted sleep); Nose symptoms (nasal discharge; nasal congestion/impaired nasal airflow; sneezing); Throat and thoracic symptoms (hoarseness; sore throat; cough). Each symptom may be graded by the following points: 0 points - absent; 1 point - mild; 2 points - moderate; 3 points - severe. The higher scores mean a worse outcome. The total score is the sum of points of each symptom graded in Symptom Assessment Scale. The maximum possible value of the total score is 30 points, the minimum possible value of the total score is 0 points. | Day 3, Day 5 | 
| Assessment of Treatment Results With Integrative Medicine Outcome Scale (IMOS) Performed by Investigator | Integrative Medicine Outcome Scale (IMOS) is used to assess treatment efficacy and has the following gradations of health condition: 0 points - absolute recovery; point - significant improvement; points - slight to moderate improvement; points - unchanged; points - decline. The results is presented in number of patients with 0 points (absolute recovery), number of patients with 1 points (significant improvement), number of patients with 2 points (slight to moderate improvement), number of patients with 3 points (unchanged), number ot patients with 4 points (decline) by day 8 according IMOS. | Day 8±1 | 
| Assessment of Treatment Results With Integrative Medicine Outcome Scale (IMOS) Performed by Parent/Adopter | Integrative Medicine Outcome Scale (IMOS) is used to assess treatment efficacy and has the following gradations of health condition: 0 points - absolute recovery; point - significant improvement; points - slight to moderate improvement; points - unchanged; points - decline. The results is presented in number of patients with 0 points (absolute recovery), number of patients with 1 points (significant improvement), number of patients with 2 points (slight to moderate improvement), number of patients with 3 points (unchanged), number ot patients with 4 points (decline) by day 8 according IMOS. | Day 8±1 | 
| Number of Cases of Antifebrile Agents Use | Number of cases of the antipyretic product (paracetamol) consumption for the entire study period | Day 8±1 | 
| Number of Patients Discontinued From the Study Due to Requirement for Antibacterial Therapy | Number of patients who discontinued from the study due to requirement for antibacterial therapy | Day 8±1 | 
| Number of Patients With Normalization of Body Temperature by 5 Day of Treatment | Axillary body temperature level ≤ 36,9 °C confirmed by two consecutive measurements (morning-evening/evening-morning will be considered as normalization of body temperature | Day 5 | 
| Number of Patients With Clinical Improvement (Symptom Assessment Scale Total Score ≤ 3) by 5 Day of Treatment | Symptom Assessment Scale (SAS) consists of 3 domains: Domain General intoxication symptoms (altered/increased activity/dysfunctional behavior; altered appetite or food refusal; unhealthy or alter from common appearance; altered or interrupted sleep); Nose symptoms (nasal discharge; nasal congestion; impaired nasal airflow; sneezing); Throat and thoracic symptoms (hoarseness; sore throat; cough). The higher scores mean a worse outcome. The total score is the sum of points of each symptom graded in Symptom Assessment Scale. The maximum possible value of the total score is 30 points, the minimum possible value of the total score is 0 points. Each symptom may be graded by the following points: 0 points - absent; 1 point - mild; 2 points - moderate; 3 points - severe. | Day 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ARI, acute respiratory infection