Efficacy and Safety of Ingavirin®, 90 mg Capsules in Patients With COVID-19

• ClinicalTrials.gov Identifier: NCT05216497
• Recruitment Status: Completed
• First Posted: January 31, 2022
• Last Update Posted: July 27, 2023
• Sponsor: Valenta Pharm JSC
• Information provided by (Responsible Party): Valenta Pharm JSC

Study Description

Brief Summary:

The primary objective of this study is to investigate the efficacy of Ingavirin®, 90 mg capsules in achieving clinical improvement of novel coronavirus disease (COVID-19) symptoms. A secondary goal of this study is to evaluate the safety of Ingavirin®, 90 mg capsules in patients with COVID-19 infection.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Ingavirin®, 90 mg capsules; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 233 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Ingavirin®, 90 mg Capsules in Patients With COVID-19
• Actual Study Start Date: October 6, 2021
• Actual Primary Completion Date: January 12, 2022
• Actual Study Completion Date: April 25, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ingavirin®, 90 mg capsules; Ingavirin®, 90 mg capsules will be administered on top of standard therapy: days 1-3: 180 mg (2 capsules once a day); days 4-7: 90 mg (1 capsule 1 time per day).	Drug: Ingavirin®, 90 mg capsules; 90-180 mg/day for 7 days on top of standard therapy
Placebo Comparator: Placebo; Placebo capsules will be administered on top of standard therapy: days 1-3: 2 capsules once a day; days 4-7: 1 capsule 1 time per day.	Drug: Placebo; 1-2 capsules for 7 days on top of standard therapy

Outcome Measures

Primary Outcome Measures :

1. Time to clinical recovery [ Time Frame: Day 2-28 ]
   Time (in hours from first dose) to clinical recovery as assessed by Hazard Ratio analysis. Clinical recovery refers to a score of ≤1 on the COVID-19 Core Symptom Rating Scale for each symptom.

Secondary Outcome Measures :

1. Assessment of patient status [ Time Frame: Day 2-28 ]
   Proportion of patients with improvement of one category or more on the World Health Organization (WHO) scale by Days 2-28; proportion of patients with deterioration by one category or more on Days 2-28; average change in WHO category by Day 2-28 from baseline; proportion of patients with progression to WHO category 3 or higher by Day 14.
2. Assessment of clinical measures [ Time Frame: Day 2-28 ]
   Proportion of patients with oxygen saturation (SpO2) ≤ 93%; proportion of patients with SpO2 ˂ 95%; average change in SpO2 compared to baseline; proportion of patients with respiratory rate (RR) > 30/min; proportion of patients with RR > 22/min; proportion of patients with RR ≤ 20/min; average change in RR; proportion of patients with fever ≤ 37.0°C; proportion of patients with fever ≤ 37.5°C; proportion of patients with temperatures ≥38.5°C; mean change in temperature from baseline.
3. Symptom Score [ Time Frame: Day 2-28 ]
   Proportion of patients with a score ≤ 1 on the Daytime and Nighttime Cough Scale; average change in cough scale score from baseline; mean time to reach ≤ 1 score on the cough scale; percentage of patients with a decrease of 1 point or more on each symptom on the COVID-19 symptom scale; percentage of patients with clinical improvement (1 point or less) on each symptom on the COVID-19 symptom scale; percentage of patients with a score ≤ 1 on each symptom on the COVID-19 symptom scale; average change in score for each symptom on the COVID-19 symptom scale from baseline; average time to reach a score ≤ 1 on each symptom on the COVID-19 symptom scale.
4. Evaluation of laboratory and instrumental examinations [ Time Frame: Day 2-28 ]
   Percentage of patients negative for Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) by Day 4, 8, 14, 21, 28 (if positive on previous examination); mean change in SARS-CoV-2 concentration by Day 8; time to SARS-CoV-2 elimination.

Other Outcome Measures:

1. Status assessment [ Time Frame: Day 2-28 ]
   Percentage of patients hospitalized during the study; length of hospitalization; proportion of patients transferred to the ICU during hospitalization; length of stay in the ICU; proportion of patients with acute respiratory distress syndrome during hospitalization; presence of fatal outcome.
2. Assessment of respiratory support [ Time Frame: Day 2-28 ]
   Percentage of patients needing oxygen therapy; percentage of patients needing high-flow oxygen therapy; percentage of patients needing noninvasive ventilation; percentage of patients needing invasive ventilation; percentage of patients needing extracorporeal membrane oxygenation (ECMO); total duration of oxygen therapy by the last day of hospitalization; total duration of high-flow oxygen therapy by the last day of hospitalization; total duration of noninvasive ventilation by the last day of hospitalization; total duration of invasive ventilation by the last day of hospitalization; cumulative duration of ECMO by the last day of hospitalization.
3. X-Ray evaluation [ Time Frame: Day 2-28 ]
   Proportion of patients with CT-1 or higher (CT-2, CT-3, and CT-4) according to lung CT data; proportion of patients with CT-0.
4. Safety assessment [ Time Frame: Day 2-28 ]
   Number and incidence of adverse events (AEs) reported during the study after study drug use and characteristics of AEs (intensity, severity, frequency, severity, expectancy, association with study therapy); number and frequency of serious adverse events (SAEs) reported during the study after the use of the study drug, and characteristics of SAEs (intensity, severity, frequency, severity, expectancy, association with the study therapy).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Written informed consent of the patient to participate in the study.
2. Patients aged 18-75 years inclusive.
3. COVID-19 diagnosis based on laboratory confirmation of SARS-CoV-2 virus, conducted within 3 days prior to the first dose of the drug. Determination of SARS-CoV-2 virus by polymerase chain reaction (PCR) or other method regulated by the actual clinical recommendations is acceptable.
4. Patients with a mild course of COVID-19 - presence of at least 2 criteria: SpO2 ≥ 95% (mandatory criterion), body temperature ˂ 38°C, respiratory rate (RR) ≤ 22/min.
5. Duration of illness not more than 3 full days from the onset of one or more of the following symptoms until the first dose of study drug: elevated body temperature; dry cough or cough with small amount of sputum; shortness of breath; myalgia; fatigue; feeling of stuffiness in the chest; sore throat; nasal congestion/rhinorrhea; headache; feeling of heat or fever; decreased sense of smell and/or taste.
6. Presence of at least two symptoms on the COVID-19 Core Symptom Rating Scale with a score of 2 or more.
7. Women only: Negative pregnancy test result. The pregnancy test need not be performed on women who are not fertile: women who are menopausal (defined as not menstruating for at least two years or more) or who have had surgical sterilization (hysterectomy, bilateral oophorectomy, tubal ligation) or have a clinical diagnosis of infertility. The presence of surgical sterilization and infertility is evaluated on the patient's word or with a document confirming this condition.
8. Women with preserved reproductive potential and men whose partners have preserved reproductive potential agree to abstain from sexual intercourse for the duration of the study.
9. Patients who are able to understand and comply with the treatment and procedures of the study.

Exclusion Criteria:

1. Known or suspected hypersensitivity to the active ingredient or any of the excipients of the study drug.
2. Known or suspected hypersensitivity to standard therapies.
3. Presence of criteria for moderate to severe disease.
4. Need for hospitalization at the time of screening or randomization.
5. Body temperature ˂ 37.5°C.
6. Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.
7. Presence of cancer within the past 2 years, or current suspicion of cancer.
8. History or current autoimmune disease.
9. Pregnancy.
10. Breastfeeding period.
11. Presence of serious lung diseases (the list can be expanded at the discretion of the investigator): moderate-to-severe bronchial asthma, severe to very severe chronic obstructive pulmonary disease (COPD), interstitial lung disease, pulmonary hypertension, pulmonary fibrosis, lung surgeries, tuberculosis (including suspected tuberculosis based on CT scan of the lungs at screening).
12. Patients with the presence of type 1 diabetes mellitus and/or decompensated type 2 diabetes mellitus.
13. Heart failure, New York Heart Association (NYHA) functional class III-IV.
14. Chronic liver failure stage II (decompensated) and higher.
15. Need for renal replacement therapy at the time of inclusion
16. History of organ transplantation.
17. History of epilepsy or need for anticonvulsant therapy.
18. Major depressive disorder, anxiety, other mental disorders requiring medication correction.
19. Acute cerebral circulation disorder, stroke, or transient ischemic attack within 90 days prior to screening.
20. Taking any antiviral and/or immunomodulatory drugs after COVID-19 manifestation.
21. Use of any immunosuppressive therapy (including tocilizumab/sarilumab) within 90 days prior to randomization, or need for immunosuppressive therapy at the time of randomization.
22. Use of anticoagulation plasma for 14 days prior to screening.
23. Use of systemic glucocorticosteroids within 90 days prior to the time of randomization, or the need to prescribe systemic glucocorticosteroids at the time of randomization.
24. History of COVID-19 vaccination.
25. Use of vaccines against viral infections within 90 days prior to the time of randomization.
26. Patients taking or having taken other experimental drugs, drugs not approved in the Russian Federation, or participating or having participated in other clinical trials within 30 days prior to screening.
27. Abuse of alcohol or psychotropic drugs and other medications currently or within the last year.
28. Patients with other serious, unstable or clinically significant medical or psychological conditions that, in the opinion of the investigator, may interfere with the patient's participation in the study.

Withdrawal Criteria:

1. Withdrawal of consent;
2. AEs that make it impossible to participate in the study or require emergency medical care in an inpatient setting (except in cases of hospitalization related to the patient's transition to a moderate to severe course of COVID-19);
3. Serious protocol violations and refusal of the participant(s) to comply with study protocol or procedures (e.g., use of protocol-prohibited therapy);
4. Pregnancy;
5. Necessity for use of medications forbidden by the protocol.
6. Participant is lost to follow-up;
7. Death of the participant;
8. Decision of the Sponsor or Investigator.

Contacts and Locations

Locations

Russian Federation

Municipal Budgetary Institution of Healthcare "Central City Hospital of Novoshakhtinsk"

Novoshakhtinsk, Rostov Region, Russian Federation, 346918

"4D Ultrasound Clinic" LLC

Pyatigorsk, Stavropol' Region, Russian Federation, 357502

"Family Clinic" LLC

Ekaterinburg, Russian Federation, 620102

Ivanovo Kuvaev Clinical Hospital

Ivanovo, Russian Federation, 153025

State Budgetary Institution of Healthcare of Moscow "City Polyclinic No. 2 of the Moscow Department of Healthcare"

Moscow, Russian Federation, 117556

Unimed-C Jsc

Moscow, Russian Federation, 119571

Ryazan State Medical University named after Academician I.P. Pavlova

Ryazan', Russian Federation, 390026

State Budgetary Institution of the Ryazan Region "Regional Clinical Hospital"

Ryazan', Russian Federation, 390039

Limited Liability Company "Medical Center "Capital-Policy"

Saint Petersburg, Russian Federation, 190013

Saint Petersburg State Budgetary Healthcare Institution "City polyclinic No. 112"

Saint Petersburg, Russian Federation, 195427

Limited Liability Company "Research Center Eco-Safety"

Saint Petersburg, Russian Federation, 196143

St. Petersburg State Budgetary Healthcare Institution "City Polyclinic No. 117"

Saint Petersburg, Russian Federation, 196143

Saint Petersburg State Budgetary Institution of Healthcare "City Pokrovskaya Hospital"

Saint Petersburg, Russian Federation, 199106

Astarta LLC

Saint Petersburg, Russian Federation, 199226

Sponsors and Collaborators

Valenta Pharm JSC

More Information

• Responsible Party: Valenta Pharm JSC
• ClinicalTrials.gov Identifier: NCT05216497
• Other Study ID Numbers: ING-03-05-2020
• First Posted: January 31, 2022
• Last Update Posted: July 27, 2023
• Last Verified: July 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Pentanedioic acid imidazolyl ethanamide; Antiviral Agents; Anti-Infective Agents