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

Sponsor

AO GENERIUM (Industry)

Overall Status

Completed

CT.gov ID

NCT04459325

Collaborator

(none)

100

Enrollment

Locations

Arms

1.6

Actual Duration (Months)

16.7

Patients Per Site

10.4

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19 Coronavirus Disease 2019	Biological: Tigerase® and best available care Other: Best available care	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 1, 2020

Actual Primary Completion Date :

Jul 20, 2020

Actual Study Completion Date :

Jul 20, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Study drug and best available care Best available care and Tigerase®/nebulised dornase alfa [2.5 mg BID] for 7 days	Biological: Tigerase® and best available care Nebulised dornase alfa [2.5 mg BID] for 7 days Other Names: Dornase Alfa Inhalation Solution and best available care
Other: Control group (best available care) Patients will receive the usual care in accordance with good practice.	Other: Best available care Patients will receive the usual care in accordance with good practice. Other Names: Standard of care

Arm

Intervention/Treatment

Experimental: Study drug and best available care

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

Biological: Tigerase® and best available care

Nebulised dornase alfa [2.5 mg BID] for 7 days

Other Names:

Dornase Alfa Inhalation Solution and best available care

Other: Control group (best available care)

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

Other: Best available care

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

Other Names:

Standard of care

Outcome Measures

Primary Outcome Measures

The proportion of patients with mechanical ventilation [Day 8]
Category change on WHO Ordinal Scale for Clinical Improvement [Day 8]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	City Clinical Hospital #15	Moscow	Russian Federation	111539
2	I.M. Sechenov First Moscow State Medical University (Sechenov University)	Moscow	Russian Federation	119991
3	City Clinical Hospital #51	Moscow	Russian Federation	121309
4	City Clinical Hospital #52	Moscow	Russian Federation	123182
5	N.V. Sklifosovsky Scientific Research Institute of First Aid	Moscow	Russian Federation	129090
6	Siberian State Medical University (SibMed)	Moscow	Russian Federation	634050