Clinical trial NCT04459325: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: 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
Lead sponsor: AO GENERIUM
Sponsor class: INDUSTRY
First posted: 2020-07-07
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: The proportion of patients with mechanical ventilation
timeFrame: Day 8
measure: Category change on WHO Ordinal Scale for Clinical Improvement
timeFrame: Day 8
Secondary outcomes:
measure: The proportion of patients with mechanical ventilation
timeFrame: Day 28
measure: Category change on WHO Ordinal Scale for Clinical Improvement
timeFrame: Day 28
measure: Proportion of patients surviving 28 days after inclusion in the study
timeFrame: Day 28
measure: Number of days of oxygen therapy during the treatment period
timeFrame: Day 8
measure: Change in C-reactive protein level
timeFrame: Days 3, 5, 8
measure: Change in oxygenation index
timeFrame: Days 3, 5, 8
measure: Change in SpO2/FiO2 index
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, 8
measure: Change in ferritin level
timeFrame: Days 3, 5, 8
measure: Change in D-dimer level
timeFrame: Days 3, 5, 8
measure: Change in neutrophil-leucocyte ratio
timeFrame: Days 3, 5, 8
measure: Change in leucocyte-C-reactive protein ratio
timeFrame: Days 3, 5, 8
measure: Change in the level of relative (%) number of lymphocytes of the general blood test
timeFrame: Days 3, 5, 8
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: City Clinical Hospital #15
city: Moscow
country: Russian Federation
facility: I.M. Sechenov First Moscow State Medical University (Sechenov University)
city: Moscow
country: Russian Federation
facility: City Clinical Hospital #51
city: Moscow
country: Russian Federation
facility: City Clinical Hospital #52
city: Moscow
country: Russian Federation
facility: N.V. Sklifosovsky Scientific Research Institute of First Aid
city: Moscow
country: Russian Federation
facility: Siberian State Medical University (SibMed)
Study officials:
affiliation: AO GENERIUM
name: Oksana A. Markova, MD
role: STUDY_CHAIR
References: