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

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19; Coronavirus Disease 2019
• Intervention / Treatment: Biological: Tigerase® and best available care; Other: Best available care

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 Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 111539
    • City clinical hospital #15
  • Moscow, Russian Federation, 121309
    • City Clinical Hospital #51
  • Moscow, Russian Federation, 119991
    • I.M. Sechenov First Moscow State Medical University (Sechenov University)
  • Moscow, Russian Federation, 123182
    • City Clinical Hospital #52
  • Moscow, Russian Federation, 129090
    • N.V. Sklifosovsky Scientific Research Institute of First Aid
  • Moscow, Russian Federation, 634050
    • Siberian State Medical University (SibMed)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The proportion of patients with mechanical ventilation	Day 8
Category change on WHO Ordinal Scale for Clinical Improvement	Day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	PaO2 / FiO2, FiO2 = fraction of oxygen in inhaled air,% PaO2 = partial pressure of oxygen in arterial blood, mm Hg	Days 3, 5, 8
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
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

Collaborators and Investigators

• Sponsor: AO GENERIUM

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2020
• Primary Completion (ACTUAL): July 20, 2020
• Study Completion (ACTUAL): July 20, 2020

Study Registration Dates

• First Submitted: July 3, 2020
• First Submitted That Met QC Criteria: July 3, 2020
• First Posted (ACTUAL): July 7, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 14, 2020
• Last Update Submitted That Met QC Criteria: October 13, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Coronavirus Infections; Respiratory Tract Diseases; COVID-19; Acute respiratory distress syndrome; Virus Diseases; Coronaviridae Infections; Respiratory Insufficiency; Acute lung injury; Dornase alfa
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections
• Other Study ID Numbers: DRN-ALI-III; #216 eff date 27.05.2020 (OTHER: Ministry of Health of Russia)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No