Efficacy of Anaferon for Children in the Treatment of Influenza and Acute Respiratory Viral Infections in Children

Study Overview
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Brief Summary
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The purpose of this study is: • To obtain additional data on therapeutic efficacy of Anaferon for children in the treatment of influenza and acute respiratory viral infections in children

Detailed Description
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The study will enroll outpatient subjects of both sexes aged 3-12 years with clinical manifestations of influenza/Acute Respiratory Viral Infections (ARVI), including fever ≥ 38.0°С having an appointment with a doctor within the first day after the illness onset. Тhe physician will collect medical history information, perform an objective examination, record the concomitant therapy, and obtain nasal swab specimens for a rapid diagnostic influenza test. If the swab is positive, the doctor shall obtain swab specimens from the nasal cavity and oropharynx (nasopharyngeal swab) for a subsequent real time reverse transcription-polymerase chain reaction (RT-PCR) to determine the viral load of influenza A and/or B virus. If the swab is negative for influenza the doctor shall collect a nasopharyngeal swab for a subsequent PCR test for other respiratory viruses. If inclusion criteria are met and exclusion criteria are absent at visit 1 (Day 1), the patient will be enrolled in the trial and randomized into one of the two groups: group 1 patients will take Anaferon for children following a 5-day regimen; group 2 patients will receive Placebo using the Anaferon for children 5-day regimen. The parent/adopter of patient will receive a diary where they should record the child's axillary temperature data in the morning and evening, and score the severity of symptoms. The subject will be monitored for 14 days (screening, randomization - 1 day, treatment - 5 days, follow-up - 1 day; late-scheduled phone visit - day 14). At Visits 2-4, the physician will document objective examination data; obtain nasopharyngeal swabs from subjects with positive influenza tests for subsequent RT-PCR to determine the viral load and its reduction in the course of treatment; monitor the prescribed and concomitant therapy, and check the patient's diary data. The phone visit will be made to elicit information from the parents regarding the patient's general health, presence/absence of secondary bacterial/viral complications, and use of antibacterial drugs. Interim statistical analysis is stipulated by the study protocol. Interim analysis will be performed using the data obtained from the examination and treatment of the protocol-defined number of patients who completed the study. Based on the expected effect, the minimum required Particular Per Protocol (pPP) sample size will be 254 patients (127 subjects in each group - Anaferon for children and Placebo).

Official Title
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International Multicenter Double-blind Placebo-controlled Randomized Parallel Group Clinical Trial of Efficacy of Anaferon for Children in the Treatment of Influenza and Acute Respiratory Viral Infections in Children

Conditions
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Influenza and Acute Respiratory Viral Infections

Intervention / Treatment
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* Drug: Anaferon for Children


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of both sexes aged 3-12 years inclusively. Diagnosis of influenza/ARVI according to physician's examination: body temperature ≥ 38.0°C at the time of examination + symptom score ≥ 4 (at least 1 systemic symptom ≥2 and 1 nasal/throat/chest symptom ≥2 or several symptoms ≥ 1 score). The first 24 hours from the beginning of manifestations of influenza/ARVI. The possibility to start therapy within 24 hours from the first symptoms of ARVI. Availability of a patient information sheet (Informed Consent form) for parents/adoptive parents for participation in the study signed by one of the parents/adoptive parents. Exclusion Criteria: Suspected pneumonia, bacterial infection or severe disease requiring antibacterial products (including sulfanilamides) starting from the first day of the disease. Clinical symptoms of severe influenza/ARVI requiring hospitalization. Suspected initial manifestations of the diseases having the symptoms similar to the ones of influenza/ARVI (other infectious diseases, influenza-like syndrome at debut of systemic connective tissue diseases, oncohematological and other diseases). Medical history of primary and secondary immunodeficiencies: а) lymphoid system immunodeficiencies (Т-cell and/or B-cell, immunodeficiencies with predominant antibody deficiency); b) phagocytic deficiencies; c) complement factor deficiency; d) combined immunodeficiencies including AIDS secondary to HIV-infection; toxic, autoimmune, infectious, radiation panleukopenic syndrome; systemic lymphocytopenic syndrome; polyclonal lymphocytic activation syndrome; postsplenectomic syndrome; congenital asplenia; immune complex pathological syndrome associated with infectious, autoimmune and allergic diseases. Medical history of sarcoidosis. Oncology. Exacerbation or decompensation of chronic diseases affecting ability to participate in the clinical study. Medical history of polyvalent allergy. Allergy/intolerance to any of the components of medications used in the treatment. Malabsorption syndrome, including congenital or acquired lactase or other disaccharidase deficiency, galactosemia. Intake of medicines listed in the section Prohibited concomitant therapy within 1 month prior to the inclusion in the study. Drug addiction, alcohol consumption at more than 2 alcohol units per day by the subject's parents/adoptive parents. Mental diseases of the subject, parents/adoptive parents. Subjects whose parents/adoptive parents, according to the investigator's point of view, will not follow the observation requirements during the study or study product dosing regimen. Participation in other clinical studies within 3 months prior to the inclusion in the study. Parent/adoptive parent of the subject is related to the investigator team of medical facility directly involved in the study or is a close relative of the investigator. Close relatives include spouse, parents, children or brothers (sisters) regardless of whether they are biological or adoptive ones. Parent/adoptive parent of the subject is working in OOO NPF Materia Medica Holding, i.e. is the company official, temporary contract worker or an appointed official responsible for the study or their close relatives.

Ages Eligible for Study
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Minimum Age: 3 Years
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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anaferon for Children<br>On day 1, five tablets are taken in the first 2 hours (one tablet every 30 min), followed by three more tablets regularly spaced during the rest of the day. From day 2 through 5, one tablet is administered three times daily. | Drug: Anaferon for Children<br>* Anaferon for children: For oral use.<br>* Other names: Anaferon for Children in tablets;|
| Placebo Comparator: Placebo<br>On day 1, five tablets are taken in the first 2 hours (one tablet every 30 min), followed by three more tablets regularly spaced during the rest of the day. From day 2 through 5, one tablet is administered three times daily. | Drug: Anaferon for Children<br>* Anaferon for children: For oral use.<br>* Other names: Anaferon for Children in tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Illness Duration | Disease duration is assessed until recovery or significant improvement. Average illness duration is defined as the interval between the start of the trial treatment and the start of the first 24-hour period in which the non-specific symptoms and nasal/ throat/ chest symptoms improve to absent or mild (Total Symptom Score of severity had decreased to ≤2 points) and body temperature returns to 37.2°C or below. Based on patient diary data. | From the time of randomization until the time of recovery/improvement (days 1-14) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Recovery/Improvement in Health | Based on Days 2, 3, 4 and 5 of observation treatment (according to the patient's diary), on days 3 and 5 of therapy (according to physician's objective examination). | on days 2, 3, 4 and 5 of the treatment | 
| Changes in Body Temperature | Changes in Body Temperature Based on Patient Diary Data | baseline and days 2, 3, 4 and 5 of observation treatment | 
| Percentage of Patients With Normal Body Temperature (≤37.0ºС) | Based on the patient diary data. Axillary temperature (morning and evening) decline to or below 37.0 ºС. | on days 2, 3, 4 and 5 of observation treatment | 
| Severity of Clinical Manifestations of Influenza / Acute Respiratory Viral Infection by Total Symptom Score. | Total Symptom Score is based on the severity of each Influenza / Acute Respiratory Viral Infection symptom. Total Symptom Score includes 13 symptoms: body temperature, non-specific symptoms (headache, chills, sweating, weakness, muscle pain, drowsiness), nasal/throat/chest symptoms. The severity of non-specific and nasal/throat/chest symptom is scored on a symptom severity scale (0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms). Minimum score=0; maximum score=39. The severity of symptoms is recorded by the doctors on the case record form on days 3, 5 and by parents/adopter on a diary card twice a day on days 2-6. | on days 2-6 of observation treatment | 
| Assessment of the Severity of Influenza Virus / Acute Respiratory Viral Infection Using the Area Under the Curve for an Overall Symptom Assessment | Total Symptom Score is based on the severity of each disease symptom. The TSS includes 13 symptoms: body temperature/fever, non-specific symptoms (headache, chills, sweating, weakness, muscle pain, drowsiness), nasal/throat/chest symptoms (runny nose, nasal congestion, sneezing, sore throat, hoarseness, cough, chest pain/tightness of the chest). Minimum score=0; maximum score=39. The area under the curve 1 = on days 1, 3, 5 and 7 on the results of doctor's examination The area under the curve 2 = based on days 1-7 on the patient diary data | on days 1-7 of observation (based on days 1-7 on the patient diary data; on days 1, 3, 5 and 7 of observation - according to physician's objective examination) | 
| Number of Intakes of Antipyretics | Number of Intakes of Antipyretics based on patient diary data | on days 1-5 of therapy | 
| Change in Viral Load During the Treatment and Follow-up Periods | Viral load is evaluated in subjects with positive influenza A and B tests. Virus load [log10 copies influenza А/В RNA per 1 mL] in nasal and pharyngeal swabs is determined using real-time PCR on days 1, 3, 5 and 7. | on days 1, 3, 5, 7 of observation treatment | 
| Percentage of Patients With Exacerbation of the Disease Course | The development of disease complications requiring antibiotics drugs or hospitalization | 14 days of observation treatment |