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

Phase 3

Completed

• Conditions: COVID-19; Coronavirus Disease 2019
• Interventions: Biological: Tigerase® and best available care; Other: Best available care

• Registration Number: NCT04459325
• Lead Sponsor: AO GENERIUM

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.

Study Timeline

• Study Start: 2020-06-01
• Status Verified: 2020-07
• Study First Submitted: 2020-07-03
• Study First Submitted QC: 2020-07-03
• Study First Posted: 2020-07-07
• Primary Completion: 2020-07-20
• Study Completion: 2020-07-20
• Last Update Submitted: 2020-10-13
• Last Update Posted: 2020-10-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study drug and best available care	Tigerase® and best available care	Best available care and Tigerase®/nebulised dornase alfa \[2.5 mg BID\] for 7 days
Control group (best available care)	Best available care	Patients will receive the usual care in accordance with good practice.

Primary Outcome Measures

Name	Time	Method
The proportion of patients with mechanical ventilation	Day 8
Category change on WHO Ordinal Scale for Clinical Improvement	Day 8

Secondary Outcome Measures

Name	Time	Method
The proportion of patients with mechanical ventilation	Day 28
Category change on WHO Ordinal Scale for Clinical Improvement	Day 28
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 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
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 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 C-reactive protein level	Days 3, 5, 8
Change in the level of relative (%) number of lymphocytes of the general blood test	Days 3, 5, 8

Trial Locations

Locations (6)

City Clinical Hospital #15; 🇷🇺 Moscow, Russian Federation

City Clinical Hospital #52; 🇷🇺 Moscow, Russian Federation

N.V. Sklifosovsky Scientific Research Institute of First Aid; 🇷🇺 Moscow, Russian Federation

Siberian State Medical University (SibMed); 🇷🇺 Moscow, Russian Federation

I.M. Sechenov First Moscow State Medical University (Sechenov University); 🇷🇺 Moscow, Russian Federation

City Clinical Hospital #51; 🇷🇺 Moscow, Russian Federation