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

COVID-19 Clinical Trial

Official title:

A Prospective Open-label Study of the Tigerase® Efficacy and Safety as Part of Complex Therapy in Patients With COVID-19

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04459325
• Other study ID #: DRN-ALI-III
• Secondary ID: #216 eff date 27
• Status: Completed
• Phase: Phase 3
• Start date: June 1, 2020
• Est. completion date: July 20, 2020

Study information

• Verified date: July 2020
• Source: AO GENERIUM
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: July 20, 2020
• Est. primary completion date: July 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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%

• ?-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

Related Conditions & MeSH terms

• Coronavirus Disease 2019
• Coronavirus Infections
• COVID-19

Intervention

Biological:
• Tigerase® and best available care
Nebulised dornase alfa [2.5 mg BID] for 7 days

Other:
• Best available care
Patients will receive the usual care in accordance with good practice.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
AO GENERIUM

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of patients with mechanical ventilation		Day 8
Primary	Category change on WHO Ordinal Scale for Clinical Improvement		Day 8
Secondary	The proportion of patients with mechanical ventilation		Day 28
Secondary	Category change on WHO Ordinal Scale for Clinical Improvement		Day 28
Secondary	Proportion of patients surviving 28 days after inclusion in the study		Day 28
Secondary	Number of days of oxygen therapy during the treatment period		Day 8
Secondary	Change in C-reactive protein level		Days 3, 5, 8
Secondary	Change in oxygenation index	PaO2 / FiO2, FiO2 = fraction of oxygen in inhaled air,% PaO2 = partial pressure of oxygen in arterial blood, mm Hg	Days 3, 5, 8
Secondary	Change in SpO2/FiO2 index	SpO2 / FiO2, FiO2 = fraction of oxygen in inhaled air,% SpO2 = hemoglobin oxygen saturation, %	Days 1, 2, 3, 4, 5, 6, 7, 8
Secondary	Change in ferritin level		Days 3, 5, 8
Secondary	Change in D-dimer level		Days 3, 5, 8
Secondary	Change in neutrophil-leucocyte ratio		Days 3, 5, 8
Secondary	Change in leucocyte-C-reactive protein ratio		Days 3, 5, 8
Secondary	Change in the level of relative (%) number of lymphocytes of the general blood test		Days 3, 5, 8