search
Back to results

Tigerase® Efficacy and Safety as Part of Complex Therapy in Patients With COVID-19

Primary Purpose

COVID-19, Coronavirus Disease 2019

Status
Completed
Phase
Phase 3
Locations
Russian Federation
Study Type
Interventional
Intervention
Tigerase® and best available care
Best available care
Sponsored by
AO GENERIUM
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring COVID-19, Coronavirus Infections, Coronaviridae Infections, Dornase alfa, Virus Diseases, Acute lung injury, Acute respiratory distress syndrome, Respiratory Insufficiency, Respiratory Tract Diseases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Written informed consent for participation in the study
  2. Men and women aged ≥18 years

  3. Laboratory-confirmed diagnosis of coronavirus infection caused by COVID19, moderate severity *

    *Criteria for moderate flow (just one point) Mandatory Criterion

    • Pneumonia Additional criteria (used to characterize the disease and are not required to determine the severity)
    • Fever above 38 ° C
    • respiratory rate more than 22 / min
    • Shortness of breath during physical exertion
    • SpO2 <95%
    • С-reactive protein (CRP) of serum more than 10 mg / l
  4. Patients with pneumonia with a stable level of hemoglobin saturation by oxygen (> 93%) on oxygen support and / or receiving respiratory support of non-invasive mechanical ventilation

Exclusion Criteria:

  1. Individual intolerance or hypersensitivity to the active or any of the excipients of the drug Tigerase®
  2. The need for invasive mechanical ventilation at the time of inclusion of the patient

  3. Patients severe condition (one of the following characteristics):

    • Respiratory distress syndrome with respiratory rate ≥30 per minute
    • Saturation of hemoglobin with oxygen ≤93% with oxygen support
  4. Patient participate in any clinical trials and / or taking the experimental drug within 30 days before inclusion this trial
  5. Severe competitive respiratory system diseases (bronchial asthma, chronic obstructive pulmonary disease - COPD, cystic fibrosis, interstitial lung disease)
  6. Positive results of laboratory testing for HIV and hepatitis B and C
  7. Life expectancy less than 12 months without COVID-19
  8. Other diseases and conditions, significant laboratory or instrumental deviation, which, according to investigator opinion, may impact the results of the study, limit the patient's participation in the trial or create an unreasonable risk for the patient
  9. Patient's unwillingness or disability to comply with the recommendations prescribed by protocol, as well as any concomitant medical or serious mental conditions that render the patient unsuitable for participation in the study, limit the legitimacy of obtaining informed consent or may affect the patient's ability to participate in the study (including disability to use a nebulizer)
  10. Positive pregnancy test in women
  11. The period of breastfeeding in women
  12. Refusal of male patients and female patients with preserved reproductive function to use adequate methods of contraception throughout the study and for at least 30 days after the end of therapy with the studied drug

Sites / Locations

  • City Clinical Hospital #15
  • I.M. Sechenov First Moscow State Medical University (Sechenov University)
  • City Clinical Hospital #51
  • City Clinical Hospital #52
  • N.V. Sklifosovsky Scientific Research Institute of First Aid
  • Siberian State Medical University (SibMed)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Study drug and best available care

Control group (best available care)

Arm Description

Best available care and Tigerase®/nebulised dornase alfa [2.5 mg BID] for 7 days

Patients will receive the usual care in accordance with good practice.

Outcomes

Primary Outcome Measures

The proportion of patients with mechanical ventilation
Category change on WHO Ordinal Scale for Clinical Improvement

Secondary Outcome Measures

The proportion of patients with mechanical ventilation
Category change on WHO Ordinal Scale for Clinical Improvement
Proportion of patients surviving 28 days after inclusion in the study
Number of days of oxygen therapy during the treatment period
Change in C-reactive protein level
Change in oxygenation index
PaO2 / FiO2, FiO2 = fraction of oxygen in inhaled air,% PaO2 = partial pressure of oxygen in arterial blood, mm Hg
Change in SpO2/FiO2 index
SpO2 / FiO2, FiO2 = fraction of oxygen in inhaled air,% SpO2 = hemoglobin oxygen saturation, %
Change in ferritin level
Change in D-dimer level
Change in neutrophil-leucocyte ratio
Change in leucocyte-C-reactive protein ratio
Change in the level of relative (%) number of lymphocytes of the general blood test

Full Information

First Posted
July 3, 2020
Last Updated
October 13, 2020
Sponsor
AO GENERIUM
search

1. Study Identification

Unique Protocol Identification Number
NCT04459325
Brief Title
Tigerase® Efficacy and Safety as Part of Complex Therapy in Patients With COVID-19
Official Title
A Prospective Open-label Study of the Tigerase® Efficacy and Safety as Part of Complex Therapy in Patients With COVID-19
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
June 1, 2020 (Actual)
Primary Completion Date
July 20, 2020 (Actual)
Study Completion Date
July 20, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AO GENERIUM

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
It is a multicenter, open-label, randomized, parallel-group study of the efficacy and safety of Tigerase® (GENERIUM JSC, Russia) with standard therapy versus standard therapy in patients with COVID-19.
Detailed Description
COVID-19 (Coronavirus disease-19) is an acute respiratory infectious disease caused by SARS-CoV-2 coronavirus. The spread of the disease quickly developed to the global pandemic in March-April 2020, and was characterized by acute respiratory distress syndrome (ARDS) in 10-15% of cases, which leads to a high frequency of hospitalization in the intensive care unit and high mortality. The search for effective treatment and reducing the severity of COVID-19 is a priority in the development of medical science. One of the key processes of the innate immune system are neutrophil extracellular traps (NET), formed by neutrophils when they eject their DNA from the cytoplasm. NET is most often described as a mechanism for capturing bacteria in order to limit their spread. In addition, NET also plays a role in antiviral immunity. In particular, viral infections lung damage is at least partially due to NET. This suggests that drug disruption of NET in COVID-19 is promising. DNase preparations, and in particular Tigerase®, are safe and effective for the treatment of cystic fibrosis and can serve as a NET destruction agent in patient with COVID-19.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, Coronavirus Disease 2019
Keywords
COVID-19, Coronavirus Infections, Coronaviridae Infections, Dornase alfa, Virus Diseases, Acute lung injury, Acute respiratory distress syndrome, Respiratory Insufficiency, Respiratory Tract Diseases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Study drug and best available care
Arm Type
Experimental
Arm Description
Best available care and Tigerase®/nebulised dornase alfa [2.5 mg BID] for 7 days
Arm Title
Control group (best available care)
Arm Type
Other
Arm Description
Patients will receive the usual care in accordance with good practice.
Intervention Type
Biological
Intervention Name(s)
Tigerase® and best available care
Other Intervention Name(s)
Dornase Alfa Inhalation Solution and best available care
Intervention Description
Nebulised dornase alfa [2.5 mg BID] for 7 days
Intervention Type
Other
Intervention Name(s)
Best available care
Other Intervention Name(s)
Standard of care
Intervention Description
Patients will receive the usual care in accordance with good practice.
Primary Outcome Measure Information:
Title
The proportion of patients with mechanical ventilation
Time Frame
Day 8
Title
Category change on WHO Ordinal Scale for Clinical Improvement
Time Frame
Day 8
Secondary Outcome Measure Information:
Title
The proportion of patients with mechanical ventilation
Time Frame
Day 28
Title
Category change on WHO Ordinal Scale for Clinical Improvement
Time Frame
Day 28
Title
Proportion of patients surviving 28 days after inclusion in the study
Time Frame
Day 28
Title
Number of days of oxygen therapy during the treatment period
Time Frame
Day 8
Title
Change in C-reactive protein level
Time Frame
Days 3, 5, 8
Title
Change in oxygenation index
Description
PaO2 / FiO2, FiO2 = fraction of oxygen in inhaled air,% PaO2 = partial pressure of oxygen in arterial blood, mm Hg
Time Frame
Days 3, 5, 8
Title
Change in SpO2/FiO2 index
Description
SpO2 / FiO2, FiO2 = fraction of oxygen in inhaled air,% SpO2 = hemoglobin oxygen saturation, %
Time Frame
Days 1, 2, 3, 4, 5, 6, 7, 8
Title
Change in ferritin level
Time Frame
Days 3, 5, 8
Title
Change in D-dimer level
Time Frame
Days 3, 5, 8
Title
Change in neutrophil-leucocyte ratio
Time Frame
Days 3, 5, 8
Title
Change in leucocyte-C-reactive protein ratio
Time Frame
Days 3, 5, 8
Title
Change in the level of relative (%) number of lymphocytes of the general blood test
Time Frame
Days 3, 5, 8

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent for participation in the study Men and women aged ≥18 years Laboratory-confirmed diagnosis of coronavirus infection caused by COVID19, moderate severity * *Criteria for moderate flow (just one point) Mandatory Criterion Pneumonia Additional criteria (used to characterize the disease and are not required to determine the severity) Fever above 38 ° C respiratory rate more than 22 / min Shortness of breath during physical exertion SpO2 <95% С-reactive protein (CRP) of serum more than 10 mg / l Patients with pneumonia with a stable level of hemoglobin saturation by oxygen (> 93%) on oxygen support and / or receiving respiratory support of non-invasive mechanical ventilation Exclusion Criteria: Individual intolerance or hypersensitivity to the active or any of the excipients of the drug Tigerase® The need for invasive mechanical ventilation at the time of inclusion of the patient Patients severe condition (one of the following characteristics): Respiratory distress syndrome with respiratory rate ≥30 per minute Saturation of hemoglobin with oxygen ≤93% with oxygen support Patient participate in any clinical trials and / or taking the experimental drug within 30 days before inclusion this trial Severe competitive respiratory system diseases (bronchial asthma, chronic obstructive pulmonary disease - COPD, cystic fibrosis, interstitial lung disease) Positive results of laboratory testing for HIV and hepatitis B and C Life expectancy less than 12 months without COVID-19 Other diseases and conditions, significant laboratory or instrumental deviation, which, according to investigator opinion, may impact the results of the study, limit the patient's participation in the trial or create an unreasonable risk for the patient Patient's unwillingness or disability to comply with the recommendations prescribed by protocol, as well as any concomitant medical or serious mental conditions that render the patient unsuitable for participation in the study, limit the legitimacy of obtaining informed consent or may affect the patient's ability to participate in the study (including disability to use a nebulizer) Positive pregnancy test in women The period of breastfeeding in women Refusal of male patients and female patients with preserved reproductive function to use adequate methods of contraception throughout the study and for at least 30 days after the end of therapy with the studied drug
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Oksana A. Markova, MD
Organizational Affiliation
AO GENERIUM
Official's Role
Study Chair
Facility Information:
Facility Name
City Clinical Hospital #15
City
Moscow
ZIP/Postal Code
111539
Country
Russian Federation
Facility Name
I.M. Sechenov First Moscow State Medical University (Sechenov University)
City
Moscow
ZIP/Postal Code
119991
Country
Russian Federation
Facility Name
City Clinical Hospital #51
City
Moscow
ZIP/Postal Code
121309
Country
Russian Federation
Facility Name
City Clinical Hospital #52
City
Moscow
ZIP/Postal Code
123182
Country
Russian Federation
Facility Name
N.V. Sklifosovsky Scientific Research Institute of First Aid
City
Moscow
ZIP/Postal Code
129090
Country
Russian Federation
Facility Name
Siberian State Medical University (SibMed)
City
Moscow
ZIP/Postal Code
634050
Country
Russian Federation

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Tigerase® Efficacy and Safety as Part of Complex Therapy in Patients With COVID-19

We'll reach out to this number within 24 hrs