Clinical Trial of Anaferon for Children Efficacy in Prevention of Influenza and Other ARVI

Study Overview
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Brief Summary
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The objective of this study is to obtain additional data on the efficacy and safety of 12-week course of therapy with Anaferon for children for prevention of influenza and other acute respiratory viral infections in children during the peaks of seasonal morbidity.

Detailed Description
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Design: an international, multicenter, double-blind, placebo-controlled, randomized study in parallel groups. The study will enroll children of either gender aged of 1 month to 6 years old. Children can participate in the study, regardless of the frequency of previous ARVI. A potential study participant should not be in the incubation (if known), prodromal, acute/subacute periods of any infectious disease (except for the recovery period). Schedule for enrollment of participants: during the period of a seasonal rise in influenza/ARVI incidence in the Russian Federation and the Republic of Uzbekistan. Screening and randomization of participants will be subject to availability of official information on the incidence of influenza/ARVI in the relevant study region. The doctor makes the first visit to the participant in the medical center or at home. After the parent/adoptive parent signs the information sheet (informed consent form), the doctor evaluates the possibility of the participant being included in the trial. If the child meets all the inclusion criteria and does not have all non-inclusion criteria, then he/she is included in the study, the doctor fills in Clinical Research Form. At visit 1 (Day 1), the participant is randomized into one of two groups: the 1st group participants will take Anaferon for children according to the preventive regimen for 12 weeks; the 2nd group participants will take Placebo according to the regimen of Anaferon for 12 weeks. In total, the study participant will be observed for 12 weeks (screening and randomization up to 1 day, preventive treatment for 12 weeks). During the observation period at 4 (Visit 2), 8 (Visit 3) and 12 (Visit 4) weeks, three visits are planned. Visits 2 (Week 4 ± 3 days) and 3 (Week 8 ± 3 days) are conducted in the form of a telephone survey of parents/adoptive parents about the participant's health status, presence/absence of symptoms of influenza/ARVI, possible use of antibacterial drugs and/or hospitalization during the course preventive therapy. Visit 4 (Week 12 ± 3 days) is carried out at home or in a medical center; the doctor collects complaints, examines the participant, registers concomitant therapy, assesses the compliance of the therapy. If in the period from 2 to 12 weeks a participant falls ill with influenza/ARVI, then he/she prematurely completes participation in the study (as having reached the primary endpoint). A participant is considered fallen ill with influenza/ARVI if the doctor identifies the following symptoms: febrile/subfebrile body temperature, presence at least one flu-like nonspecific symptom (decreased activity/impaired behavior/weakness; headache; chills) and at least one respiratory symptom (runny nose; nasal stuffiness; hoarseness/husky voice; sore throat; cough). In this case, the doctor makes an unscheduled visit (at home or in a medical center), which is final. During the visit, the doctor carries out the procedures of Visit 4. A nasopharyngeal swab is taken to identify the most common pathogens of influenza/ARVI. If ARVI/influenza occurs within the first seven days from the onset of preventive therapy, the disease will not be recorded as an adverse event and will not be taken into account to evaluate the efficacy of the study drug, since an early manifestation of influenza/ARVI may indicate that the participant was included in the study when he/she was in the incubation period of an infectious disease. During the study, concomitant therapy for underlying chronic conditions, as well as routine vaccination of the participant, are allowed, with the exception of the drugs indicated in the section Prohibited Concomitant Treatment.

Official Title
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International Multicenter Double-bind Placebo-controlled Randomized Parallel-group Clinical Trial of Anaferon for Children Efficacy in Prevention of Influenza and Other Acute Respiratory Viral Infections in Children During the Peaks of Seasonal Morbidity

Conditions
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Preventive Medicine

Intervention / Treatment
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* Drug: Anaferon for children
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children of either gender aged from 1 month to 6 years old. The absence of clinical symptoms of any infectious disease, but not earlier than 14 days from its onset. Seasonal rise in ARVI incidence, confirmed by official information. An information sheet (Informed Consent form) for the subject participation in the clinical trial signed by one parent/adopter of the patient. Exclusion Criteria: Acute or subacute period of infectious disease of any etiology (viral, bacterial, fungal, etc.) and localization (including upper and lower respiratory tract infection, meningitis, sepsis, otitis media, urinary tract infection, intestinal infection, etc.). History of (verified previously) or current suspected conditions such as: primary or secondary immunodeficiency; bronchopulmonary dysplasia, primary ciliary dyskinesia, cystic fibrosis, other chronic pulmonary diseases; malformations of the respiratory and ENT organs (ear, throat, mouth, tongue, larynx, trachea, neck and salivary and thyroid glands, etc.); immunopathological diseases (including Marshall syndrome, Behсet's syndrome, Kawasaki disease, etc.); hematological diseases (including agranulocytosis, leukemia); oncologic conditions. Exacerbated or decompensated of chronic diseases affecting the patienrt's ability to participate in the clinical trial. Malabsorption syndrome, including congenital or acquired lactase or another disaccharide deficiency, galactosemia. Allergy/intolerance to any component of the study drug. Course administration of the drug products specified in the section 'Prohibited concomitant medications' within 2 weeks prior to enrollment. Children whose parents/adopter parents will fail to comply with the observation requirements of the trial or with the intake regimen of the study drug, from the investigator's point of view. Participation in other clinical trials within 3 month prior to enrollment in the study. The patient's parent/adopter parent is a member of the research team of the investigational site directly involved in the study or a close relative of an investigator. Close relatives are defined as husband/wife, parents, children, brothers (sisters) regardless of whether they are biological or adopted. The patient's parent/adopter parent works for OOO NPF MATERIA MEDICA HOLDING (i.e., the company's employee, part-time employee under contract or appointed official in charge of the trial, or their immediate family).

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anaferon for children<br>Tablet for oral use. One tablet per intake, once daily (approximately at the same time). The product is administered outside a meal (in the interval between meals or 15 min prior to meal or fluid intake), the tablets should be held in mouth until complete dissolution. For young children (aged 1 month to 3 years old), the tablet is recommended to be dissolved in a small amount (1 tablespoon) of drinking water of room temperature. | Drug: Anaferon for children<br>* Tablet for oral use.<br>|
| Placebo Comparator: Placebo<br>Tablet for oral use. Placebo using Anaferon for children scheme. | Drug: Placebo<br>* Tablet for oral use.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Taking the First Dose of the Study Drug to the Onset of Influenza/ARVI Symptoms. | Based on medical records. | in 12 weeks of the treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Children Not Falling Ill With Influenza or Another ARVI. | Based on medical records. Influenza/ARVI criteria are the following: febrile/subfebrile body temperature, presence at least one flu-like nonspecific symptom (decreased activity/weakness, headache, and chills), and at least one respiratory symptom (runny nose, nasal stuffiness, hoarseness/husky voice, sore throat, and cough). | in 12 weeks of the treatment | 
| Percentage of Children With the Symptoms Requiring Antibacterial Therapy. | Based on medical records. Percentage of children with the symptoms of a respiratory or ear-nose-throat bacterial infection requiring antibacterial therapy. | in 12 weeks of the treatment | 
| Percentage of Children Requiring Hospitalized for Influenza/ARVI. | Based on medical records. Percentage of children hospitalized for influenza/ARVI or their complications. | in 12 weeks of the treatment | 
| Presence and Type of Adverse Events (AE). | Based on medical records. Presence and type of adverse events, their severity, relation to investigational drug, outcomes. | in 12 weeks of the treatment |