Study to Evaluate the Efficacy, Safety, and Tolerability of the Ingavirin Forte Capsules (Valenta Pharm JSC) at Different Doses in Subjects With Influenza and Other Acute Respiratory Viral Infections.

A Multicenter, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of the Investigational Product Ingavirin Forte Capsules (Valenta Pharm JSC) at Different Doses in Subjects With Influenza and Other Acute Respiratory Viral Infections.

The objective of this study is to investigate the efficacy, safety, and tolerability of investigational product Ingavirin forte capsules (Valenta Pharm JSC) administered at different doses compared with medicinal product Ingavirin, 90 mg, capsules (Valenta Pharm JSC) in subjects with influenza or other acute respiratory viral infections (ARVIs).

Inclusion Criteria:

1. Voluntarily and personally signed Informed Consent Form (ICF) by a participant obtained prior to the conduct of any study-related procedure;

2. Males and females aged 18 to 65 years (inclusive) at the time of signing the ICF;

3. Subjects with influenza or other acute respiratory viral infections confirmed by polymerase chain reaction (PCR);

4. Presence of clinically significant signs of influenza or acute respiratory viral infections at screening:

   • Body temperature >38,0 °С at randomization, with no intake NSAID within 12 hours before randomization;
   • Presence of at least two of the following symptoms of influenza or other acute respiratory viral infections (cough, rhinorrhea, sore throat, or a throat irritation) each rated non less than 6 points on a numeric rating scale (NRS);
   • Presence of at least one of the following systemic manifestations of influenza or other acute respiratory viral infections (headache, myalgia, or general weakness) rated non less than 6 points on a numeric rating scale (NRS).

5. Duration of illness from symptoms onset to administration of the first dose of investigational medical product or comparator is ≤ 48 hours;

6. No clinical indications for hospitalization at the time of study enrollment;

7. Consent to use adequate contraceptive methods throughout the study and for 30 days after study completion. The follwing subjects are eligible for inclusion in the study:

   • Females of childbearing potential must have a negative pregnancy test and use one of the folliwing adequate contraceptive methods: sexual abstinence, condom combined with spermicide or hormonal contraceptives, contraceptive subdermal implant, intrauterine hormonal system, intrauterine device. Females not of childbearing potential (i.e., with a history of hysterectomy, bilateral oophorectomy, bilateral tubal ligation, comfirmed infertility, or ≥ 2 of menopause) are also eligible for participation;
   • Males with reptoductive potential must use one of the folliwing adequate contraceptive methods: sexual abstinence, condom combined with spermicide or hormonal contraceptives. Males with infertility or a history of vasectomy are also eligible for participation;

Exclusion Criteria:

1. Clinically significant allergic history;
2. Hypersensitivity to active substances of medical produtcs Ingavirin and Ingavirin forte, and/or to any excipient contaned in the investigational medicinal product or comparator;
3. Intolerance to active substances of medical produtcs Ingavirin and Ingavirin forte, and/or to any excipient contaned in the investigational medicinal product or comparator;
4. Known galactose intolerance, lactase deficiency, or glucose-galactose malabsorption;
5. Clinical suspicion of pneumonia of any etiology, or other bacterial infection (e.g. sinusitis, otitis media, urinary tract infection, meningitis, sepsis) requiring initiation for antibacterial therapy;
6. Nasal obstruction due to structural pathology, such as sequelae of nasal trauma, nasal polyps, septal deviation, or other organic causes;
7. History of vasomotor rhinitis;
8. Administration of antibiotics, antiviral (including Ingavirin), or immunomodulatory agents within 48 hours prior to study, and/or anticipated need for any of these agents during the study;
9. Vaccination within 90 days prior to study enrollment;
10. Uncontrolled diabetes mellitus;
11. Obesity, class II or III (body mass index ≥35 kg/m²);
12. Pregnancy or lactation;
13. Positive test for SARS-CoV-2 at screening;
14. History of autoimmune diseases;
15. Current or past HIV, syphilis, hepatitis B and/or C, or tuberculosis;
16. Known or suspected history of alcohol, psychotropic drug, or substance abuse or dependence;
17. History of chronic respiratory disease, including but not limited to: chronic obstructive pulmonary disease (COPD), asthma, chronic bronchitis, diffuse panbronchiolitis, pulmonary emphysema, or pulmonary fibrosis;
18. Chronic heart failure, New York Heart Association (NYHA) functional class III or IV;
19. Current or past psychiatric disoder;
20. Any clinically significant cardiovascular, renal, hepatic, gastrointestinal , endocrine, or neurological disoder, including severe uncompensated chronic conditions (e.g., chronic kidney disease, chronic liver disease) or acute illness, or any other medical or psychiatric condition that, in investigator's opinion, could pose a safety risk to the subject if they participate in the study;
21. Subject's refusal to use an adequate method of contraception or to practice continuous sexual abstinence throughout the study and for 30 days after study completion;
22. Participation in another clinical trial within 3 months prior to screening;
23. Other conditions which, in the judgment of the investigator, could compromise the subject's participation in the study or pose an undue risk.

Exclusion Criteria:

1. Subject's decision to withdraw from the study (withdrawal of informed consent);

2. Investigator's decision to discontinue the subject from the study in the subject's best interest;

3. Investigator-determined need for a concomitant therapy explicitly prohibited by the protocol of clinical study;

4. Subject's use of a therapy prohibited by the protocol;

5. Positive urine test for beta-human chorionic gonadotropin (β-hCG) in females of childbearing potential;

6. Lack of adequate cooperation by the subject with the investigator during the study;

7. Emergence during the study of conditions or events that jeopardize subject safety (e.g., hypersensitivity reactions, serious adverse events [SAEs]) or, in the investigator's medical judgment, worsen the subject's prognosis or preclude further participation in the clinical study;

8. Incorrect inclusion of a subject who does not meet the protocol-specified inclusion and/or exclusion criteria;

9. Major deviation from the treatment regimen, defined as:

   • Missing two or more consecutive doses of the investigational medicinal product (IMP) or comparator;
   • Total intake of fewer than 80% or more than 120% of the planned total number of capsules (full course includes 10 capsules);

10. Confirmed diagnosis of COVID-19;

11. Occurrence during the study of any other condition that precludes adherence to the protocol;

12. Subject's death.