Efficacy and Safety of Ingavirin®, Syrup, 30 mg/5 ml, in Children With Influenza and Other Acute Respiratory Viral Infections

Influenza, Human Clinical Trial

Official title:

A Multicenter, Double-blind, Randomized, Placebo-controlled Study of the Efficacy and Safety of Ingavirin®, Syrup, 30 mg/5 ml, in Children Aged 6 Months to 2 Years With Influenza and Other Acute Respiratory Viral Infections Against Standard Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05269290
• Other study ID #: ING-03-04-2020
• Status: Completed
• Phase: Phase 3
• Start date: September 23, 2021
• Est. completion date: July 15, 2022

Study information

• Verified date: July 2023
• Source: Valenta Pharm JSC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is planned to evaluate the therapeutic efficacy and safety of Ingavirin®, syrup, 30 mg/5 ml, in the treatment of influenza or other acute respiratory infections in children from 6 months to 2 years compared with placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: July 15, 2022
• Est. primary completion date: April 29, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 2 Years

Eligibility

Inclusion Criteria:

1. Patient's parent/adoptive parent's informed consent form voluntarily signed by the patient's parent/adoptive parent;

2. Boys and girls aged 6 months - 2 years 11 months 14 days, inclusive, with the following clinical signs of acute respiratory infections/flu: body temperature above 38.0 °C but not higher than 39.0 °C (without taking antipyretics within the last 8 h) at the time of screening/randomization; at least one of the respiratory manifestations of acute respiratory infection/influenza (cough, runny nose/ stuffy nose) of at least 2 points on a 4-point scale; decrease in the child's daytime activity and change in nighttime sleep, as compared with the state before the illness;

3. There were no indications for hospitalization at the time of inclusion in the study;

4. Duration of illness from manifestation of symptoms to inclusion in the study not more than 48 hours.

Exclusion Criteria:

1. Presence of at least one of the epidemic signs: return from an overseas trip 14 days prior to the onset of symptoms; having close contact in the last 14 days with a person under observation for COVID-19 who has subsequently become ill; having close contact within the past 14 days with a person who has a laboratory-confirmed diagnosis of COVID-19;

2. Positive result of laboratory testing for SARS-CoV-2 RNA using nucleic acid amplification techniques or antigen SARS-CoV-2 antigen using an immunochromatographic assay at the time of screening;

3. Severe general intoxication syndrome (severe agitation with seizure syndrome and loss of consciousness against a background of hyperthermia);

4. Hemorrhagic syndrome (nasal bleeding, blood in sputum, vomit and stool, hemorrhagic rash), disseminated intravascular coagulation syndrome (DIC) or Hasser syndrome with the formation of acute renal failure;

5. Diffuse cyanosis or pallor;

6. Symptoms of pneumonia and possible acute respiratory distress syndrome (ARDS): cough with frothy sputum with blood, shortened pulmonary sound on percussion, a large number of different-caliber moist rales and abundant crepitation on auscultation, a sharp drop in blood pressure (BP), deafness of heart tones and arrhythmia;

7. Phenomena of respiratory distress combined with any of the following symptoms:

grunting breathing, blowing of the wings of the nose when breathing, nodding movements (head movements synchronized with breathing); BPM in a child aged 6-11 months > 50 per minute, child over 1 year old > 40 per minute; lower chest retraction when breathing; blood oxygen saturation (SpO2) < 92% when breathing room air;

8. Moderate acute respiratory infections (fever = 38.5 °C) with exacerbation of comorbidities;

9. Presence of any of the following symptoms: inability to drink/breastfeed; drowsiness or unconsciousness; respiratory rate less than 30 per minute or apnea; heart failure phenomena; severe dehydration;

10. Febrile seizures, including a history of seizures; known intolerance to the active ingredient or excipient of the study drug or placebo components, paracetamol;

12. Lactose intolerance, lactase deficiency or glucose-galactose malabsorption. 13. Taking antibiotics, antivirals, or immunomodulatory drugs within < 48 h prior to the study and/or plans to use these groups of drugs (other than the study drug) during the study; 14. Use of systemic, inhaled, or nasal glucocorticosteroids within 30 days prior to the study and/or plans to use glucocorticosteroids (except topical cutaneous agents) during the study; 15. Failure to withdraw for the duration of the study other medications that may affect the outcome of this study, such as antiviral medications, or medications that are incompatible with the study therapy (see "prohibited concomitant therapies"); 16. Patient's participation in any other clinical trial within 90 days prior to inclusion in the study;

17. Any cardiovascular, renal, hepatic, gastrointestinal (GI), endocrine, or nervous system disease, severe decompensated chronic or acute disease, or any other condition/disease that, in the opinion of the investigating physician, would make it unsafe for the patient to participate in the study; 18. Having any vaccinations administered to the patient within 14 days prior to inclusion in the study; 19. Diabetes mellitus; 20. Clinical suspicion of pneumonia or other bacterial infections (including sinusitis, otitis media, urinary tract infection, meningitis, sepsis, etc.) requiring administration of antibacterial drugs; 21. Patients who have had surgery within 30 days prior to the Screening Visit and patients who are scheduled to have surgery, including diagnostic procedures, or a hospital stay during the study; 22. Suspicion of hemophagocytic syndrome; 23. Increased seizure activity in the history; 24. The presence of cancer, HIV infection, tuberculosis, including in the anamnesis; 25. Suspected low compliance of the parent/adopter with the child's treatment and recording of required parameters in the Patient Diary, or inability to perform these procedures and comply with restrictions according to the study protocol (e.g., due to mental illness).

Withdrawal Criteria:

1. Identification of a probable or confirmed case COVID-19;

2. Signs of complications of viral infection, including signs of secondary bacterial infection;

3. The investigating physician decides that the patient must be excluded for the patient's own benefit;

4. Withdrawal of informed consent by the parent or adoptive parent;

5. Individual intolerance to the study drug;

6. Development of NS requiring withdrawal of study drug/placebo;

7. Erroneous inclusion (for example, the patient was included in violation of the inclusion/inclusion criteria of the protocol);

8. Patient receives/needs additional treatment that may affect study outcome or patient safety (see "prohibited concomitant therapies");

9. Persistence of nasal congestion longer than 10 days, worsening of condition after the first week of illness, facial pain;

10. Patient's development of the conditions described in the criteria for exclusion;

11. Development of hemorrhagic syndrome (including DIC): nosebleed, hemorrhagic rash on the face, neck, chest, and upper extremities, hemorrhages into the mucous membrane of the mouth and nose, the back of the throat, conjunctivae, blood in vomit, hemoptysis, etc.);

12. A pronounced intoxication syndrome with the development of encephalic or meningoencephalic reactions (delirium, hallucinations, seizures, confusion or loss of consciousness, vomiting);

13. Hemophagocytic syndrome;

14. Other conditions or events that, in the opinion of the investigating physician, require exclusion of the patient from the study.

Related Conditions & MeSH terms

• Acute Respiratory Infection
• Common Cold
• Communicable Diseases
• Infections
• Influenza, Human
• Respiratory Tract Infections
• Virus Diseases

Intervention

Drug:
• Ingavirin®, syrup, 30 mg/5 ml
A dose will be based on the body weight; Ingavirin® will be administered once a day on top of standard therapy.
• Placebo
Placebo will be administered once a day on top of standard therapy.

Locations

Country	Name	City	State
Russian Federation	Federal Research and Clinical Center of Physical and Chemical Medicine of the Federal Medical and Biological Agency	Odintsovo	Moscow Region
Russian Federation	City Pediatric Outpatient Clinic number 5	Perm
Russian Federation	Professors' Clinic LLC.	Perm
Russian Federation	City Polyclinic No. 45 of Nevsky District	Saint Petersburg
Russian Federation	PiterKlinika LLC	Saint Petersburg
Russian Federation	St. Petersburg State Budgetary Healthcare Institution "Children's City Polyclinic No. 44"	Saint Petersburg
Russian Federation	Uromed LLC	Smolensk
Russian Federation	Bashkir State Medical University	Ufa

Sponsors (1)

Lead Sponsor	Collaborator
Valenta Pharm JSC

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time of symptoms/events resolution	Time, in hours, from the first administration of the drug until all of the following symptoms/events have resolved (if each symptom/event has been achieved for at least 24 hours): Fever; Cough and/or runny nose/nasal congestion; Child's return to normal daytime activity and normal nighttime sleep (as assessed by the parent/adopter).	From Day 1 up to Day 13-14 (visit 4)
Secondary	Time to fever relief	Number of hours elapsed from the first administration of the medication to the time of persistent normalization of the temperature, i.e., the moment when the body temperature is < 37.5 °C during the day without the use of antipyretic medication	From Day 1 up to Day 13-14 (visit 4)
Secondary	Time to cough relief	Number of hours from the first dose to the time the coughing cough has gone away, i.e. the parent/adoptive parent rates the symptom as 0-1 during the day and records this in the patient's diary	From Day 1 up to Day 13-14 (visit 4)
Secondary	Time to cough/nasal congestion relief	Number of hours from first medication administration to cough/congestion cessation, i.e., when parent/adopter rates severity of this symptom during the day at 0-1 point and records this in patient diary	From Day 1 up to Day 13-14 (visit 4)
Secondary	Frequency of complications of acute viral infection and influenza	Acute otitis media, viral and bacterial pneumonia, exacerbation of chronic conditions such as bronchial asthma and urinary tract infections), toxemia [septic-like syndrome], acute stenotic laryngotracheitis	From Day 1 up to Day 13-14 (visit 4)
Secondary	Frequency of patients with PCR-confirmed viral infection	PCR-confirmed acute respiratory infections/flu by visits 1, 2, 3	Day 1, Day 3-4 (visit 2), Day 6-7 (visit 3)
Secondary	Need for paracetamol or ibuprofen	Daily dose on study days 1-7	Days 1-7
Secondary	Safety - Number of adverse events (AEs)	Total number of AEs stratified by severity and frequency	From Day 1 up to Day 13-14 (visit 4) or up to early termination visit within time frame of the study
Secondary	Safety - Adverse reactions	Frequency of adverse reactions	From Day 1 up to Day 13-14 (visit 4) or up to early termination visit within time frame of the study
Secondary	Safety - Serious adverse events (SAEs)	Frequency of serious adverse events (SAEs) associated with study drug/placebo use	From Day 1 up to Day 13-14 (visit 4) or up to early termination visit within time frame of the study
Secondary	Safety - Percentage of patients with AEs	Percentage of patients with at least one AE	From Day 1 up to Day 13-14 (visit 4) or up to early termination visit within time frame of the study
Secondary	Safety - Percentage of patients who interrupted treatment	Percentage of patients who interrupted treatment due to AE	From Day 1 up to Day 13-14 (visit 4) or up to early termination visit within time frame of the study
Secondary	Safety - Frequency of complications	Frequency of complications	From Day 1 up to Day 13-14 (visit 4) or up to early termination visit within time frame of the study
Secondary	Safety - Frequency of worsening	Frequency of worsening of the disease course	From Day 1 up to Day 13-14 (visit 4) or up to early termination visit within time frame of the study
Secondary	Safety - Frequency of hospitalization	Frequency of need for hospitalization	From Day 1 up to Day 13-14 (visit 4) or up to early termination visit within time frame of the study