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

Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06383819
• Other study ID #: Long-Cov-III-21
• Status: Completed
• Phase: Phase 3
• Start date: April 8, 2022
• Est. completion date: December 31, 2023

Study information

• Verified date: April 2024
• Source: NPO Petrovax
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical study is to evaluate the efficacy and safety of Longidaza®, lyophilizate 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 392
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 PE 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 bovgialuronidase 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.

Related Conditions & MeSH terms

• COVID-19
• Fibrosis
• Lung Diseases
• Lung Diseases, Interstitial
• Lung; Disease, Interstitial, With Fibrosis
• Polymyositis

Intervention

Drug:
• Longidaza®
dose 3000 IU intramuscularly once every 5 days, 15 injections
• Placebo
intramuscularly once every 5 days, 15 injections

Locations

Country	Name	City	State
Russian Federation	State Autonomous Healthcare Institution of the Sverdlovsk region "Aramil City Hospital"	Aramil
Russian Federation	Private healthcare institution "Clinical Hospital "RZD-Medicine" of the city of Chelyabinsk"	Chelyabinsk
Russian Federation	State Budgetary Healthcare Institution "Regional Clinical Hospital No. 3"	Chelyabinsk
Russian Federation	Ural research Institute of Phthisiopulmonology	Ekaterinburg
Russian Federation	Alliance Biomedical-Ural Group LLC	Izhevsk
Russian Federation	Federal State Budgetary Educational Institution of Higher Education "Kazan State Medical University" of the Ministry of Health of the Russian Federation	Kazan
Russian Federation	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"	Kazan
Russian Federation	Medical Center Rhevma-Med LLC	Kemerovo
Russian Federation	State Autonomous Healthcare Institution "Kuzbass Clinical Hospital of Emergency Medical Care named after M.A. Podgorbunsky"	Kemerovo
Russian Federation	Federal State Budgetary Educational Institution of Higher Education "Kirov State Medical University" of the Ministry of Health of the Russian Federation	Kirov
Russian Federation	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	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	I.M. Sechenov First Moscow State Medical University	Moscow
Russian Federation	Unimed-S Zao	Moscow
Russian Federation	ErSi Medical LLC	Novosibirsk
Russian Federation	Professorial Clinic LLC	Perm
Russian Federation	Astarta LLC	Saint Petersburg
Russian Federation	Eco-Safety Research Center LLC	Saint Petersburg
Russian Federation	Energia Zdoroviya LLC	Saint Petersburg
Russian Federation	Federal State Budgetary Institution "Consultative and Diagnostic Center with Polyclinic" of the Office of the President of the Russian Federation	Saint Petersburg
Russian Federation	Medical Center Reavita Med SPb LLC	Saint Petersburg
Russian Federation	Reavita Med SPb Medical Center LLC	Saint Petersburg
Russian Federation	St. Petersburg State Budgetary Healthcare Institution "City Consultative and Diagnostic Center No. 1".	Saint Petersburg
Russian Federation	St. Petersburg State Budgetary Healthcare Institution "Consultative and Diagnostic Center No.85"	Saint Petersburg
Russian Federation	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	Saratov
Russian Federation	Regional State budgetary healthcare institution "Clinical Hospital No. 1"	Smolensk
Russian Federation	Federal State Budgetary Educational Institution of Higher Education "Siberian State Medical University" of the Ministry of Health of the Russian Federation	Tomsk
Russian Federation	Budgetary healthcare institution of the Voronezh region "Voronezh Regional Clinical Hospital No. 1"	Voronezh
Russian Federation	Medical Center for Diagnosis and Prevention plus LLC	Yaroslavl
Russian Federation	The State Autonomous Healthcare Institution of the Yaroslavl region "Clinical Hospital No. 9"	Yaroslavl

Sponsors (1)

Lead Sponsor	Collaborator
NPO Petrovax

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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