Efficacy and Safety of Longidaza® for the Treatment of Patients With Residual Changes in the Lungs After COVID-19

Multicenter, Randomized, Double-blind, Placebo-controlled Parallel-group Study to Evaluate the Efficacy and Safety of Longidaza® for the Treatment of Patients With Residual Changes in the Lungs After COVID-19

The goal of this clinical study is to evaluate the efficacy and safety of Longidaza®, lyophilisate for preparation of solution for injection, at a dose of 3000 IU compared to placebo in the treatment of adult patients with residual changes in the lungs after COVID-19 infection

Study Overview

• Status: Completed
• Conditions: Fibrosis; Lung Diseases, Interstitial; Lung; Disease, Interstitial, With Fibrosis; Post-Acute COVID-19 Syndrome; Lung Disease With Polymyositis
• Intervention / Treatment: Drug: Longidaza®; Drug: Placebo

Detailed Description

The main objective of the clinical study was to prove the superiority of the efficacy of the drug Longidaza® over placebo when used in adult patients with residual changes in the lungs after COVID-19 infection based on the dynamics of respiratory function

• Study Type: Interventional
• Enrollment (Actual): 392
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Aramil, Russian Federation, 624000
    • State Autonomous Healthcare Institution of the Sverdlovsk region "Aramil City Hospital"
  • Chelyabinsk, Russian Federation, 454000
    • Private healthcare institution "Clinical Hospital "RZD-Medicine" of the city of Chelyabinsk"
  • Chelyabinsk, Russian Federation, 454021
    • State Budgetary Healthcare Institution "Regional Clinical Hospital No. 3"
  • Ekaterinburg, Russian Federation, 620039
    • Ural research Institute of Phthisiopulmonology
  • Izhevsk, Russian Federation, 426061
    • Alliance Biomedical-Ural Group LLC
  • Kazan, Russian Federation, 420012
    • Federal State Budgetary Educational Institution of Higher Education "Kazan State Medical University" of the Ministry of Health of the Russian Federation
  • Kazan, Russian Federation, 420012
    • Federal State Budgetary Educational Institution of Higher Education "Kazan State Medical University" of the Ministry of Health of the Russian Federation. The State Autonomous healthcare institution "Hospital for War Veterans of Kazan"
  • Kemerovo, Russian Federation, 650000
    • State Autonomous Healthcare Institution "Kuzbass Clinical Hospital of Emergency Medical Care named after M.A. Podgorbunsky"
  • Kemerovo, Russian Federation, 650070
    • Medical Center Rhevma-Med LLC
  • Kirov, Russian Federation, 610027
    • Federal State Budgetary Educational Institution of Higher Education "Kirov State Medical University" of the Ministry of Health of the Russian Federation
  • Moscow, Russian Federation, 119991
    • I.M. Sechenov First Moscow State Medical University
  • Moscow, Russian Federation, 101990
    • Federal State Budgetary Institution "National Medical Research Center for Therapy and Preventive Medicine" of the Ministry of Health of the Russian Federation
  • Moscow, Russian Federation, 111123
    • Federal Budgetary Institution of Science "Central Research Institute of Epidemiology" of the Federal Service for Supervision of Consumer Rights Protection and Human Well-being
  • Moscow, Russian Federation, 119571
    • Unimed-S Zao
  • Novosibirsk, Russian Federation, 630005
    • ErSi Medical LLC
  • Perm, Russian Federation, 614070
    • Professorial Clinic LLC
  • Saint Petersburg, Russian Federation, 199226
    • Astarta LLC
  • Saint Petersburg, Russian Federation, 194156
    • Energia Zdoroviya LLC
  • Saint Petersburg, Russian Federation, 194354
    • Medical Center Reavita Med SPb LLC
  • Saint Petersburg, Russian Federation, 194354
    • Reavita Med SPb Medical Center LLC
  • Saint Petersburg, Russian Federation, 194354
    • St. Petersburg State Budgetary Healthcare Institution "City Consultative and Diagnostic Center No. 1".
  • Saint Petersburg, Russian Federation, 196143
    • Eco-Safety Research Center LLC
  • Saint Petersburg, Russian Federation, 197110
    • Federal State Budgetary Institution "Consultative and Diagnostic Center with Polyclinic" of the Office of the President of the Russian Federation
  • Saint Petersburg, Russian Federation, 198260
    • St. Petersburg State Budgetary Healthcare Institution "Consultative and Diagnostic Center No.85"
  • Saratov, Russian Federation, 410012
    • Federal State Budgetary Educational Institution of Higher Education "Saratov State Medical University named after V.I. Razumovsky" of the Ministry of Health of the Russian Federation
  • Smolensk, Russian Federation, 214006
    • Regional State budgetary healthcare institution "Clinical Hospital No. 1"
  • Tomsk, Russian Federation, 634050
    • Federal State Budgetary Educational Institution of Higher Education "Siberian State Medical University" of the Ministry of Health of the Russian Federation
  • Voronezh, Russian Federation, 394066
    • Budgetary healthcare institution of the Voronezh region "Voronezh Regional Clinical Hospital No. 1"
  • Yaroslavl, Russian Federation, 150040
    • Medical Center for Diagnosis and Prevention plus LLC
  • Yaroslavl, Russian Federation, 150042
    • The State Autonomous Healthcare Institution of the Yaroslavl region "Clinical Hospital No. 9"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male and female patients aged 18 to 80 years, who signed an informed consent form.
2. The condition after infection with COVID-19, documented in the period from 1 to 12 months before screening (ICD-10: U07.1, U07.2), including accompanied by hospitalization of the patient.
3. The presence of a negative result of the polymerase chain reaction test (PCR) during screening and an express test for the SARS-CoV-2 antigen at visit 2.
4. The presence of respiratory symptoms (at least dyspnea), while the severity of dyspnea on the mMRC during screening is ≥ 1 point.
5. The value of hemoglobin oxygen saturation: SpO2 < 95% at rest at the screening; and/or desaturation (decrease of SpO2 by ≥ 4% in the 6MWT relative to the value at rest) at the screening.
6. The presence of residual changes in the lung parenchyma characteristic of previous COVID-19 infection, > 10% of the area, according to CT at the screening
7. Respiratory dysfunction of the restrictive type at the screening: FVC < 80%, FVC 1 / FVC > 70%.

Exclusion Criteria:

1. A history of chronic respiratory diseases (interstitial lung disease, chronic obstructive pulmonary disease, bronchial asthma, bronchiectasis, lung cancer).
2. Clinical signs or anamnesis data on the presence of diseases that, according to the researcher, can lead to restrictive changes in respiratory function (pronounced kyphoscoliosis, pleural effusion, neuromuscular diseases), pathological obesity, etc.
3. Clinical signs or anamnesis data on the presence of unstable angina pectoris, stable angina pectoris of high functional class, clinically significant cardiac arrhythmias, chronic heart failure, pulmonary hypertension, suffered pulmonary embolism or acute myocardial infarction in within 6 months prior to screening.
4. Dyspnea of any other etiology: thyrotoxicosis, anemia (hemoglobin less than 100 g/l), pathological obesity (BMI ≥ 40 kg/m2), metabolic acidosis, neuromuscular diseases according to anamnesis or screening examination.
5. The presence of an acute infectious process of any etiology and localization.
6. Allergic reactions to the administration of azoximer bovhyaluronidase or an auxiliary component of the studied drug (mannitol) in the anamnesis.
7. Clinical signs of pulmonary hemorrhage and/or hemoptysis during examination and in the anamnesis.
8. Confirmed eye injuries with vitreous hemorrhage during the last 6 months according to the medical history.
9. Malignant neoplasms of any localization in the anamnesis, with the exception of in situ carcinoma, which required only surgical treatment.
10. Renal failure.
11. Taking drugs of prohibited therapy since the start of screening in this study.
12. Serological test positive for HIV infection, viral hepatitis B and C.
13. Pregnancy or breastfeeding.
14. Participation in clinical trials of an experimental drug within 30 days prior to screening for participation in the current study.
15. Any other medical or social conditions that, in the opinion of the research physician, do not allow the patient to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Longidaza®; Bovhyaluronidase azoximer, 3000 IU	Drug: Longidaza®; dose 3000 IU intramuscularly once every 5 days, 15 injections; Other Names: Bovhyaluronidase azoximer
Placebo Comparator: Placebo; The placebo will contain no active pharmaceutical ingredients.	Drug: Placebo; intramuscularly once every 5 days, 15 injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Forced vital capacity (FVC) (visit 4)	Change in the FVC (%) compared with the initial data according to spirometry data after completion of the course of therapy	Baseline to Day 71±1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Slowing the decline in respiratory function	Slowing the decline in respiratory function (FVC (%) compared with the initial data after the end of the observation period	Baseline to Day 180±3
Change in FVC (visit 5)	Change in the FVC (%) compared with the initial data after the end of the observation period	Baseline to Day 180±3
The proportion of patients with an increase in the FVC (%)	The proportion of patients with an increase in the FVC (%) by 10% or more compared to the initial values after Visit 4 and Visit 5	Baseline, Day 71±1, Day 180±3
Dynamics of hemoglobin oxygen saturation (SpO2)	Dynamics of SpO2 values at rest after Visit 4 and Visit 5	Baseline, Day 71±1, Day 180±3
The proportion of patients with SpO2 ≥ 93% and < 93%	The proportion of patients with SpO2 value at rest ≥ 93% and < 93% after Visit 4 and Visit 5	Baseline, Day 71±1, Day 180±3
The proportion of patients with desaturation	The proportion of patients with desaturation, defined as a decrease in SpO2 by ≥ 4% after 6-minute walk test (6MWT) after Visit 4 and Visit 5	Baseline, Day 71±1, Day 180±3
The proportion of patients with an increase in the distance of 6MWT	The proportion of patients with an increase in the distance of 6MWT by 50 m or more after Visit 4 and Visit 5	Baseline, Day 71±1, Day 180±3
The proportion of patients with a decrease in the severity of dyspnea on the Borg scale	The proportion of patients with a decrease in the severity of dyspnea on the Borg scale by ≥ 2 points after Visit 4 and Visit 5	Baseline, Day 71±1, Day 180±3
The proportion of patients with a decrease in the severity of dyspnea on the Modified Medical Research Council Dyspnea Scale (mMRC)	The proportion of patients with a decrease in the severity of dyspnea on the mMRC by ≥ 1 point after Visit 4 and Visit 5	Baseline, Day 71±1, Day 180±3
Change in cough severity on the Visual Analogue Scale (VAS)	Change in cough severity on the VAS after Visit 4 and Visit 5	Baseline, Day 71±1, Day 180±3
Change in the assessment of the quality of life according to the European Quality of Life 5-Dimension 5-Level Questionnaire (EuroQol-5D-5L)	Change in the assessment of the quality of life according to the EuroQol-5D-5L after Visit 4 and Visit 5	Baseline, Day 71±1, Day 180±3

Collaborators and Investigators

• Sponsor: NPO Petrovax
• Investigators: Principal Investigator: Sergey Avdeev, DM, I.M. Sechenov First Moscow State Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2022
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: April 24, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 25, 2024

Study Record Updates

• Last Update Posted (Actual): June 3, 2025
• Last Update Submitted That Met QC Criteria: May 28, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: COVID-19; Lung Diseases
• Additional Relevant MeSH Terms: Post-Infectious Disorders; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Pathologic Processes; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Myositis; COVID-19; Post-Acute COVID-19 Syndrome; Lung Diseases; Fibrosis; Lung Diseases, Interstitial; Polymyositis
• Other Study ID Numbers: Long-Cov-III-21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No